Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Anemia is a well-known disorder in CKD dogs, but its frequency in AKI dogs has been poorly investigated. The aim of the present study was to retrospectively evaluate the frequency of anemia, its degree of severity, and regeneration rate in relation to IRIS grade, etiology, therapy, and out-come. Medical records of dogs (2017-2023) with historical, laboratory, and ultrasound findings consistent with AKI were retrospectively reviewed. According to etiology, AKI was classified as ischemic/inflammatory (IS), infectious INF), nephrotoxic (NEP), obstructive (OBS), and unknown (UK). AKI dogs were also classified according to therapeutical management (medical vs hemo-dialysis), survival to hospital discharge (survivors vs non-survivors). AKI dogs were considered anemic in case of HCT 38 g/dL). Regeneration rate was considered absent (RET< 60,000/μL), mild 61,000- 150,000/μL), and moderate (> 150,000/μL). A total of 120 AKI dogs were included the study, and anemia was found in 86/120 dogs (72%). The severity of anemia was mild in 32/86 dogs (37%), moderate in 40/86 dogs (47%), severe in 11/86 dogs (13%), and very severe in 3/86 (3%). Anemia was normo-chromic in 71/86 dogs (83%), hyperchromic in 12/86 dogs (14%), and hypochromic in 3/86 dogs (3%). Normocytic anemia was present in 56/86 dogs (65%), microcytic anemia in 27/86 dogs (31%), and macrocytic anemia in 3/86 dogs (4%). Non-regenerative anemia was found in 76/86 dogs (88%). The frequency of anemia increased significantly (p

There is evidence that kidney involvement is frequently observed in COVID-19 patients, and can manifest as mild proteinuria to advancing acute kidney injury (AKI). One of the mechanisms is microvascular and macrovascular thrombosis caused by the hypercoagulation phase of the disease. Thromboelastography (TEG) is a valuable examination to detect significant hemostatic abnormalities, including the hypercoagulable state. This study analyzed the coagulation profiles, including TEG parameters, in COVID-19 patients who developed AKI compared to those who did not during their intensive care unit (ICU) stay, to identify predictors of AKI. Our single-center cohort retrospective study involved adult patients of COVID-19 in the ICU of Sardjito Hospital in Yogyakarta, Indonesia between May and September 2021. Patients were divided into two groups of AKI and non-AKI based on 2012 KDIGO definition and the elaboration by Indonesian Society of Nephrology. Variables showing a significant difference in the two groups were then analyzed using univariate and multivariate binary logistic regression. A total of 60 COVID-19 patients were included in the study, and 35% of them developed AKI. Compared to non-AKI patients, those with AKI exhibited a greater prevalence of diabetes mellitus (66.7% versus 35.9%, P = 0.023), higher D-Dimer levels (970 versus 685 ng/mL, P = 0.045), and higher values in TEG parameters of maximum amplitude/MA (74.6 versus 65.9 mm, P = 0.001) and coagulation index/CI (2.3 versus 1.0, P = 0.033). TEG parameter of MA emerged as the sole significant predictor for the development of AKI (OR, 6.33; 95% CI, 1.56 to 25.64). Our study validated the kidney involvement of COVID-19 infection, and showed that diabetes mellitus, high D-Dimer levels, and hypercoagulability serve as prominent risk factors in the development of AKI. Furthermore, TEG parameter of MA exceeding 70 mm is the single independent significant predictor of AKI.

The composition of the gut microbiota varies among end-stage renal disease (ESRD) patients on the basis of their mode of renal replacement therapy (RRT), with notably more pronounced dysbiosis in those undergoing hemodialysis (HD). Interventions such as dialysis catheters, unstable hemodynamics, strict dietary restrictions, and pharmacotherapy significantly alter the intestinal microenvironment, thus disrupting the gut microbiota composition in HD patients. The gut microbiota may influence HD-related complications, including cardiovascular disease (CVD), infections, anemia, and malnutrition, through mechanisms such as bacterial translocation, immune regulation, and the production of gut bacterial metabolites, thereby affecting both the quality of life and the prognosis of patients. This review focuses on alterations in the gut microbiota and its metabolites in HD patients. Additionally, understanding the impact of the gut microbiota on the complications of HD could provide insights into the development of novel treatment strategies to prevent or alleviate complications in HD patients.

Acute kidney injury (AKI) is a clinical syndrome where a rapid decrease in kidney function and/or urine output is observed, which may result in the imbalance of water, electrolyte and acid base, and is associated with poor prognosis and prolonged hospitalization. Therefore, early diagnosis and treatment to avoid the severe AKI stage is important. While several biomarkers, such as urinary L-FABP and NGAL, can be clinically useful, there is still no gold standard for early detection of AKI and there are limited therapeutic options against AKI. miRNAs are non-coding and single-stranded RNAs that silence their target genes in the post-transcriptional process and are involved in a wide range of biological processes. Recent accumulated evidence has revealed that miRNAs may be potential biomarkers and therapeutic targets for AKI. In this review article, we summarize the current knowledge about miRNAs as promising biomarkers and potential therapeutic targets for AKI, as well as the challenges in their clinical use.

Biomarkers have become an important tool in the diagnosis and management of cardio renal syndromes (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. These biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS and discusses their potential as valuable clinical tools for personalized medicine in the future.

This article provides a thorough overview of biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI), acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical application. The pathophysiological mechanisms underlying AKI, AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses, with the impact on renal injury. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and cellular senescence of renal cell. Key signaling pathways, such as Wnt/β-Catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The Renin-Angiotensin-Aldosterone System (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating oxidative stress and cellular changes that promote fibrosis. Clinical evidence suggests RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

Introduction: Decompensated heart failure (HF) is a complex and debilitating syndrome, which constitutes a severe emergency condition with high morbidity and mortality. The kidneys play fundamental roles in the pathophysiology of HF and, in the context of decompensations, acute kidney injury (AKI) has a bilateral cause-and-effect relationship, which can significantly worsen prognosis. However, the interaction between AKI and decompensated HF is poorly understood. Objective: This study aimed to assess the occurrence of AKI in patients hospitalized due to decompensated HF and to analyze its prognostic impact during hospitalization. Methods: Prospective single-center observational study that included patients hospitalized due to decompensated HF in a tertiary-level teaching hospital, conducted between July 2017 and January 2020. Patients who developed AKI during hospitalization were compared with those who did not develop it, until hospital discharge or death. AKI was defined as a serum creatinine increase greater than or equal to 0.3 mg/dl in 48 hours, a 1.5-fold increase in baseline creatinine in seven days or urinary volume <0.5 ml/kg/h during six hours, according to the Acute Kidney Injury Network (AKIN) criteria. The endpoints analyzed were death, need for invasive mechanical ventilation (IMV) and length of hospital stay. The Wilcoxon, Mann-Whitney and unpaired student t tests were used. Results: Ninety-nine patients were included, with a mean age of 65.4 ± 14 years, of which 47 (47.5%) were male and 52 (52.5%) were female. Reduced ejection fraction was observed in 77.8% of patients, whilst 22.2% had a diagnosis of HF with preserved EF. The decompensation clinical classifications were: dry and warm = 7 (7.1%), wet and warm = 72 (72.7%), wet and cold = 15 (15.1%) and dry and cold = 5 (5.1%). The average left ventricular ejection fraction was 38.3% ± 15. AKI ocurred in 22 patients (22.2%). Comparison between patients who evolved with and without AKI showed higher mortality (36.4% vs 10.4%, p = 0.004) and the need for IMV (54.5% vs 13%, p = 0.0001) in the first group. There was no significant difference regarding the length of in-hospital stay (22.9 ± 19 vs 18.8 ± 16 days, p = 0.26). Conclusions: The occurrence of AKI was frequent in patients with decompensated HF requiring hospitalization, affecting approximately one out of five patients. This complication was significantly associated with increased mortality and the need for IMV during hospitalization.

Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To contain the virus, numerous preventive measures have been taken including isolation of patients, careful infection control, social distancing, and taking vaccine. So far, new confirmed and death cases are still increasing. SARS-CoV-2 invades cells by using the angiotensin converting enzyme 2 (ACE2). ACE2 is an essential enzyme of the renin-angiotensin system (RAS) which converts angiotensin II (Ang II) to angiotensin (1-7). ACE2 is expressed in different organs, including lung, heart, and kidney. A high number of COVID-19 patients developed kidney injury has been reported. Renal impairment and acute injury are associated with mortality of COVID-19, which is 14-16 times higher than other general patients. Acute Kidney Injury has been occured in 2.9 up to 43% of intensive care unit patients. The increasing evidence show that the components of RAS can activate the complement cascade, and cytokines production. Kidney injury caused by SARS-CoV-2 is related mainly to systemic and local inflammation. Moreover, the uncontrolled immune responses mediated by SARS-CoV-2 including hypercytokinaemia, secondary hemophagocytic lymphohistiocytosis, antibody dependent enhancement, complement system, and phagocytic cells activation can contribute in the virus pathogenesis leading to associated renal dysfunction. However, the role and crosstalk between of RAS components and immune response in mediating kidney injury remain undefined. In this review, we focus on the recent studies to provide the pathogenesis of SARS-CoV-2 interacting with RAS and immune responses to mediate kidney injury.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, specially, in patients under-lying pre-existing renal function impairment, cardiovascular disease or diabetes that could rap-idly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network) and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on tra-ditional “gold standard” biomarkers known as serum creatinine, glomerular filtration rate and urinary output, new reliable serum and urinary biomarkers are still needed for an effective uni-fied diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination, as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Acute kidney injury (AKI), especially if recurring represents a risk factor for future chronic kidney disease. In intensive care units, increased intraabdominal pressure is well-recognized as a significant contributor of AKI. However, the importance of transiently increased intra-abdominal pressures procedures is less commonly appreciated during laparoscopic surgery, the use of which has rapidly increased over the last few decades. Unlike the well-known autoregulation of the renal cortical circulation, medulla perfusion is modulated via partially independent regulatory mechanisms and strongly impacted by changes in venous and lymphatic pressures. In our review paper, we will provide a comprehensive overview of this evolving topic, covering a broad range from basic pathophysiology up to and including current clinical relevance. Key regulators of oxidative stress such as ischemia-reperfusion injury, the activation of inflammatory response and humoral changes interacting with procedural pneumoperitoneum formation and AKI risk will be recounted. Moreover, we present an in-depth review of the interaction of pneumoperitoneum formation with general anesthetic agents and animal models of congestive heart failure. A better understanding of the relationship between pneumoperitoneum formation and renal perfusion will support basic and clinical research, leading to improved clinical care and collaboration among specialists.

Novel coronavirus infection is a recent infective agent that causes severe potentially fatal pneumonia. The clinical presentation includes asymptomatic infection, severe pneumonia, and acute respiratory failure. Data pertaining to the clinical presentation of solid organ transplant recipients are scarce. Two cases of novel coronavirus infection in two recipients of renal transplant with variable clinical presentations and outcomes are reported. The first patient presented with progressive respiratory symptoms, acute renal failure, and passed away, whereas the second one, although presented with respiratory tract symptoms and hypoxemia remained stable and exhibited an excellent clinical recovery despite recent reception of thymoglobulin induction. This paper reports rare cases of novel coronavirus infection in renal transplant recipients. For an enhanced insight of the novel coronavirus infection and acute kidney injury on the clinical presentation, severity, and outcome in solid organ transplant recipients, further investigations are required.

There are several Amazonian plant species with potential pharmacological validation for the treatment of acute kidney injury, a condition in which the kidneys are unable to adequately filter the blood, resulting in the accumulation of toxins and waste in the body. Scientific production on plant compounds capable of preventing or attenuating acute kidney injury, caused by several factors, including ischemia, toxins and inflammation, has shown promising results in animal models of acute kidney injury and some preliminary studies in humans. Despite the popular use of Amazonian plant species for kidney disorders, further pharmacological studies are needed to identify active compounds and subsequently conduct more complex preclinical trials. Thus, this review aimed to describe the pharmacological properties of phytocompounds from Amazonian plant species and their effectiveness in the prevention and treatment of Acute Kidney Injury. (AKI). The classes of Amazonian plant compounds with significant biological activities most evident in the consulted literature were alkaloids, flavonoids, tannins, steroids and terpenoids. An expressive phytochemical and pharmacological relevance of the studied species was identified, although many of them with insufficiently explored potential, mainly in face of AKI, a clinical condition with high morbidity and mortality.

Cadmium (Cd) is a metal with no nutritional or physiological value, but is found in most people because it is a contaminant in nearly all food types. The intestinal absorption rate determines the body burden of Cd because humans lack a physiologic mechanism for excretion of the metal. Most acquired Cd accumulates in the kidneys, in which the Cd content increases through age 50 but falls thereafter. The decline from maximal kidney content is probably due to release of Cd from injured tubular cells into urine and replacement of destroyed nephrons by scar tissue. Chronic kidney disease is diagnosed when the estimated glomerular filtration rate (eGFR) falls below 60 mL/min/1.73 m2, or when albuminuria is present. Albuminuria is defined as an albumin-to-creatinine ratio ≥ 30 mg/g creatinine in women or ≥ 20 mg/g creatinine in men that persists for at least 3 months. Generally, Cd-induced reductions in eGFR are not reversible, and Cd nephropathy may progress to end-stage kidney disease. There is no evidence that elimination of current environmental exposure can reverse Cd nephropathy, and no theoretical reason to believe that such a reversal is possible. This review provides an update of knowledge concerning CKD in population environmentally exposed to Cd. Special attention is devoted to mechanisms of Cd-induced albuminuria concurrently with eGFR reductions, and the difficult challenge of exposure guidelines sufficient to eliminate the risk of Cd-induced CKD is addressed.

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3^- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8^- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

ABSTRACTCaffeine is known to impair both growth and development in the model social amoeba Dictyostelium discoideum. However, little is known about the transcriptional regulation in response to caffeine treatment in Dictyostelium. In yeast cells, caffeine mimics the effect of rapamycin in inhibiting mTORC1 activity. Here, we investigated whether changes in growth and development of Dictyostelium in the presence of caffeine or rapamycin are mediated by mTORC1 and/or mTORC2. Results: Treatment of wild type cells with caffeine or rapamycin resulted in severely impaired growth and in the formation of small aggregates in comparison to untreated cells. rip3‾ cells (lacking a mTORC2 component) and lst8‾cells (lacking a component of both mTOR complexes) showed higher and slower growth rates, respectively, in comparison to parental AX3 cells. Parental AX3 and rip3‾ cells displayed similar sensitivity to rapamycin and caffeine, while lst8‾ cells were more sensitive to these compounds. When developed in the presence of caffeine or rapamycin, AX3 cells formed aggregates after a long delay. Caffeine did not alter the morphology of small rip3‾ mounds and lst8‾ cells continued to remain solitary. However, in the presence of 1µM rapamycin rip3‾cells failed to form mounds while AX3 cells streamed and formed aggregates. Complementation of lst8‾ cells with the wild type lst8 gene rescued the aggregation phenotype. cDNA microarray analysis to uncover the spectrum of differentially regulated genes in response to caffeine treatment revealed 104 and 193 differentially expressed genes at 3-and 6-hours of development, respectively, in comparison to control cells. After 6 hours of starvation in the presence of caffeine, 25 genes encoding ribosomal proteins and 4 encoding elongation factors were up regulated. Furthermore, we identified that upon caffeine treatment at the 3- and 6-hours’ time points, 12 (10 up and 2 down) and 21 (13 up and 8 down) genes, respectively, encoding proteins involved in early development. Conclusion: We conclude that caffeine and rapamycin have similar effects in decreasing the growth rate and in reducing the aggregate size of D. discoideum. Studies with lst8‾ and rip3‾ cells suggest that these compounds affect cell growth and aggregation by acting on both mTOR complexes, mTORC1 and mTORC2. Analysis of the differentially expressed genes after caffeine treatment suggests a key role of these genes in growth and aggregation.

Background/Objectives: Infectious Endocarditis often requires surgical intervention, with postoperative acute kidney injury (AKI) posing a significant concern. This retrospective study aimed to investigate AKI incidence, its impact on short-term mortality, and identify modifiable factors in patients with endocarditis scheduled for valve surgery. Methods: This single center study enrolled 130 consecutive endocarditis patients from 2013 to 2021 undergoing valve surgery. Creatinine levels were monitored pre- and postoperatively, and AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patient demographics, comorbidities, procedural details, and complications were recorded. Primary outcomes included AKI incidence, the relevance of creatinine levels for AKI detection, and the association of AKI with 30-, 60- and 180-day mortality. Modifiable factors contributing to AKI were explored as secondary outcomes. Results: Postoperatively, 35.4% developed AKI. The highest creatinine elevation occurred on the 2nd postoperative day. Best predictive value for AKI was a creatinine level of 1.35 mg/dl on the 2nd day (AUC: 0.901; sensitivity: 0.89, specificity: 0.79). Elevated creatinine levels on the 2nd day were robust predictors for short-term mortality at 30, 60 and 180 days postoperatively (AUC ranging from 0.708 to 0.789). CK-MB levels at 24 hours postoperatively and minimum hemoglobin during surgery were identified as independent predictors for AKI in logistic regression. Conclusions: This study highlights the crucial role of creatinine levels in predicting short-term mortality in surgical endocarditis patients. A specific threshold (1.35 mg/dl) provides a practical marker for risk stratification, offering insights for refining perioperative strategies and optimizing outcomes in this challenging patient population.

Background: The systemic inflammatory index (SII) is a new inflammatory marker that has been the subject of various studies in diseases with chronic inflammation. Diabetic nephropathy is also a disease that goes with chronic inflammation. We aimed to evaluate the relationship be-tween SII and diabetic nephropathy. Methods: Patients with diabetes who applied to our outpatient clinic are included in the study. Diabetic patients are divided into two groups: those with diabetic nephropathy and those with-out. In addition, healthy individuals who applied to our clinic for general check-ups during these dates are included as control group. The SII values and other characteristics of the three study groups are compared. Results: The median SII value for those with DKI was 584 (178-4819); for those without DKI, it was 282 (64-618); and for the control group, it was 236 (77.5-617) (p<0.001). SII was significantly and positively correlated with BMI, weight, blood glucose, HbA1c, CRP and creatinine, and neg-atively correlated with glomerular filtration rate (GFR) value. The SII value higher than 336 has 75% sensitivity and 70% specificity in detecting DKI. Conclusion: The SII value could predict diabetic kidney injury in diabetics and it could be used as an adjunctive diagnostic tool.

Aim: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in hepatopancreaticobiliary (HPB) surgeries. Material and Methods: All the HPB surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and fisher t test wherever approptiate and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant. Results: We performed 195 HPB surgeries between April 2018 to March 2020, Which included 114 biliary surgeries, 57 liver surgeries and 23 pancreas surgeries. 10 patients developed Acute Kidney Injuries. (AKI) On Univariate analysis AKI was associated with open surgeries, intra operative hypotension and liver surgeries, higher ASA grade, increase operative time, more blood products used, higher CDC grade of surgery and more hospital stay before diagnosis of AKI. However on multivariate analysis only higher ASA score independently predicted Acute Kidney Injury. (p=0.003, odds ratio 15.659, 95% confidence interval 2.54-93.36). AKI was also significantly associated with mortality. (p <0.0001). Conclusion: Pre operative higher ASA grade independently predicted post operative acute kidney injury. Post operative AKI is significantly associated with mortality.

The standard of care measures for kidney function, proteinuria, and serum creatinine (SCr) are poor predictors of early stage kidney disease. Measures that can detect chronic kidney disease in its earlier stages are needed to enable therapeutic intervention and reduce adverse outcomes of chronic kidney disease. We have developed the Kidney Injury Test (KIT) and a novel KIT Score based on the composite measurement and validation of multiple biomarkers across a unique set of 397 urine samples. The test is performed on urine samples that require no processing at the site of collection and without target sequencing or amplification. We sought to verify that the pre-defined KIT test, KIT Score, and clinical thresholds correlate with established chronic kidney disease (CKD) and may provide predictive information of early kidney injury status above and beyond proteinuria and renal function measurements alone. Statistical analyses across six DNA, protein, and metabolite markers were performed on a subset of residual spot urine samples with CKD that met assay performance quality controls from patients attending the clinical labs at the University of California, San Francisco (UCSF) as part of an ongoing IRB approved prospective study. Inclusion criteria included selection of patients with confirmed CKD and normal healthy controls; exclusion criteria included incomplete or missing information for sample classification, logistical delays in transport/processing of urine samples or low sample volume, and acute kidney injury. Multivariate logistic regression of kidney injury status and likelihood ratio statistics were used to assess the contribution of the KIT Score for prediction of kidney injury status and stage of CKD as well as assess the potential contribution of the KIT Score for detection of early stage CKD above and beyond traditional measures of renal function. Urine samples were processed by a proprietary immunoprobe for measuring cfDNA, methylated cfDNA, clusterin, CXCL10, total protein, and creatinine. The KIT Score and stratified KIT Score Risk Group (High versus Low) had a sensitivity and specificity for detection of kidney injury status (healthy or CKD) of 97.3% (95% CI: 94.6%–99.3%) and 94.1% (95% CI: 82.3%–100%). In addition, in patients with normal renal function [eGFR ≥ 90], the KIT Score clearly identifies those with predisposing risk factors for CKD, which could not be picked up by eGFR or proteinuria (p < 0.001). The KIT Score uncovers a burden of kidney injury that may yet be incompletely recognized, opening the door for earlier detection, intervention and preservation of renal function.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Background: Diagnosis of acute kidney injury (AKI) relies on serum creatinine (SCr) changes. This study investigated if urinary aminopeptidases are early and predictive biomarkers of cardiac surgery associated-AKI (CSA-AKI). Methods: Glutamyl aminopeptidase (GluAp), alanyl aminopeptidase (AlaAp), dipeptidyl peptidase-4 (DPP4), proteinuria, albuminuria, N-acetyl-β-D-glucosaminidase (NAG) and neutrophile gelatinase-associated lipocalin (NGAL) were measured in urine samples from 44 patients at arrival in Intensity Care Unit (ICU) after cardiac surgery. Sensitivity, specificity, positive and negative predictive value for diagnosis of stages 1, 2 and 3 of AKI were analyzed for the highest quartile of each marker. We also studied the relationship with SCr after surgery, 6- and 12-months glomerular filtration rate (GFR) and other long-term events over the next 5 years. Results: GluAp diagnosed the maximal number of patients that developed stage 2 or 3 of AKI, increasing diagnostic sensitivity from 0 to 75 %. Besides, GluAp and DPP4 was related to the decrease in GFR at 6- or 12-months after surgery. Conclusions: Urinary aminopeptidases are a potential tool for the early diagnosis of CSA-AKI, being GluAp the most effective marker for diagnosing stages 2 or 3 of AKI at ICU admission. GluAp and DPP4 serve as predictive biomarkers for the decrease in GFR.

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

Dendritic cells (DCs) are unique immune cells that can link innate and adaptive immune responses and Immunometabolism greatly impacts their phenotype. Rapamycin is a macrolide compound that has immunosuppressant functions and is used to prevent graft loss in kidney transplantation. The current study evaluated the therapeutic potential of ex-vivo Rapamycin treated DCs to protect kidneys in a mouse model of acute kidney injury (AKI). For the Rapamycin single (S) treatment (Rapa-S-DC), Veh-DCs were treated with Rapamycin (10 ng/ml) for 1 hour before LPS. In contrast, Rapamycin multiple (M) treatment (Rapa-M-DC) were exposed to 3 treatments over 7 days. Only multiple ex-vivo Rapamycin treatments of DCs induced a persistent reprogramming of mitochondrial metabolism. These DCs had 18-fold more mitochondria, had almost 4-fold higher oxygen consumption rates, and produced more ATP compared to Veh-DCs (Veh treated control DCs). Pathway analysis showed IL10 signaling as a major contributing pathway to the altered immunophenotype after Rapamycin treatment compared to vehicle with significantly lower cytokines Tnfa, Il1b, and Il6, while regulators of mitochondrial content Pgc1a, Tfam, and Ho1 remained elevated. Critically, adoptive transfer of Rapamycin treated DCs to WT recipients 24 hrs before bilateral kidney ischemia significantly protected the kidneys from injury with a significant 3-fold improvement in kidney function. Last, the infusion of DCs containing higher mitochondria numbers (treated ex-vivo with healthy isolated mitochondria (10 µg/ml) one day before) also partially protected the kidneys from IRI. These studies demonstrate that pre-emptive infusion of ex-vivo reprogrammed DCs that have higher mitochondria content has therapeutic capacity to induce an anti-inflammatory regulatory phenotype to protect kidneys from injury.

Background: Handheld cameras may increase access to teleretinal diabetic retinopathy screenings (TDRS), as they are more economical and nimbler than traditional desktop cameras. However, their use in safety-net clinical settings is less understood. Methods: The Los Angeles County Department of Public Health collaborated with the Los Angeles County Department of Health Services (DHS) to pilot the use of handheld cameras in DHS’s TDRS program. This study assessed screening metrics and interviewed TDRS coordinators and photographers about their experiences using these cameras. Results: Handheld cameras are harder to operate and performed less optimally on key screening metrics (e.g., image quality) compared to desktop cameras. However, this challenge appeared to be linked to the selected model, rather than to all handheld cameras. The adoption of handheld cameras in DHS was aided by their integration into an existing agency infrastructure that already supports the use of desktop cameras; these operational supports include an established workflow, a data platform, and experienced photographers. Conclusions: The use of handheld cameras for TDRS is a promising practice for assuring equitable access to screenings. Handheld cameras are portable, smaller in size, and lower in cost than desktop cameras. Future projects should invest in and assess the performance of higher-quality models of these cameras, especially their use in safety-net clinical settings.

Ischemia-reperfusion injury (IRI) is a complex pathophysiological process that can lead to severe and irreversible consequences, including the complete loss of renal function. While standardized strategies for preventing IRI during "back-table" and cold preservation are available, various intraoperative prevention methods have been proposed to mitigate the harmful effects of warm ischemia and reperfusion of the kidney. These methods include pharmacological agents, mechanical interventions, and surgical techniques such as renal capsulotomy, ischemic preconditioning, venous blood reperfusion, renal perfusion, and the use of tissue engineering techniques like mesenchymal stromal/stem cells and/or decellularization. In this comprehensive analysis, we provide a detailed overview of pharmacological agents and intraoperative methods and approaches for the prevention and treatment of renal IRI. We begin by discussing the mechanisms of IRI and the challenges of preventing it during surgery. Then using a bibliometric analysis and molecular docking of brand-new legends we showed eplerenone have the most binding affinity to Aldehyde dehydrogenase (AD), Estrogen receptor (ER), Klotho protein, Mineralocorticoid receptor (MR), and Toll-like receptor 4 (TLR4) for preventing IRI comparing with other available therapeutics, Benzodioxole, Hydrocortisone, Indoles, Nicotinamide adenine dinucleotide, and Niacinamide. Next, we provide a comprehensive analysis of the potential benefits and limitations of various prevention strategies, including an in-depth discussion of the mechanisms of action of pharmacological agents, mechanical interventions, and surgical techniques. Furthermore, we introduce a novel scoring system for the prevention methods of kidney IRI, which takes into account the effectiveness, feasibility, and safety of each method. We then analyze the current state of clinical research in this area and discuss the implications of these methods for future clinical practice. Overall, this article provides a valuable resource for clinicians and researchers seeking to prevent and treat renal IRI in surgical settings, and introduces a new scoring system that can be used to guide the selection of the most effective and safe prevention methods.

Background: Limited data exist on postoperative acute kidney injury (AKI) in patients underwent esophageal cancer surgery. The purpose of the study was to evaluate the incidence, risk factors and consequences of postoperative acute kidney after esophagectomy. Methods: This was a retrospective cohort study. The study was conducted in a tertiary specialized cancer center in Italy. All patients undergoing elective esophageal cancer surgery between 2016 and 2021 were included in the study. AKI was defined according to Kidney Disease: Improving Global Outcomes criteria (both serum creatinine and urine output), within 48 hours after surgery. Preoperative and intraoperative data were registered. We also collected data concerning progression of AKI, need for kidney replacement therapy, mortality, medical (pulmonary, cardiovascular, septic) and surgical complications within 30 days from surgery, as well as length of hospital stay. Results: Incidence of postoperative AKI was 32%. The independent risk factors were body mass index and the invasive surgical approach. Persistent AKI accounted for 15% of the cases and it was associated with increased risk of major cardiovascular events (odds ratio 4.14, 95% CI 1.05-15.8, p-value 0.036), pulmonary complications (OR 3.67, 95% CI 1.04-14.9, p-value 0.050) and increased length of hospital stay (AME 7.2, 0.5-13.9, p-value 0.035). Conclusions: Postoperative AKI is common after esophageal cancer surgery. BMI and totally invasive surgical approach are independent risk factors. Persistent AKI lasting more than 48 hours increased the risk for cardiovascular and pulmonary complications, with prolonged length of hospital stay.

Acute kidney injury (AKI) is a highly prevalent and a critical complication of cardiac surgery (CS). Serum lactate levels (sLac) have consistently shown an association with morbimortality after CS. We performed a cross-sectional study including 264 adult patients that had a cardiac surgery between January and December 2020. Logistic regression analysis was performed to determine factors associated with AKI development. We measured the postoperative levels of sLac to all participants immediately after CS (T0) and after 4 hours (T4) of the surgical intervention. Linear regression model was carried out to identify the factors influencing both levels of sLac. We identified four risk predictors of AKI; one was preoperative (atrial fibrillation), one intraoperative (cardiopulmonary bypass time), and two were postoperative (length of hospital stay and postoperative sLac). T0 and T4 sLac levels were higher among CS-AKI patients than in Non-CS-AKI. Postoperative sLac levels were significant independent predictors of CSA-AKI and the sLac levels are influenced by length of hospital stay, the number of packed red blood cells transfused and the use of furosemide in CS-AKI patients. These findings may facilitate the earlier identification of patients susceptible to AKI after CS.

Acute kidney injury (AKI) is a common complication post-cardiac surgery, impacting short- and long-term survival. Free light chains (FLCs) are being explored as markers for assessing kidney damage risk. A study aimed to validate early AKI detection by studying FLCs (kappa, lambda, and kappa/lambda ratio) in serum and saliva samples. Clinical data was collected from 149 patients who underwent cardiac surgery in Baghdad. Ninety of these patients provided saliva samples in addition to serum samples for free light chain evaluation. Patients were grouped by proteinuria severity. Serum kappa levels were significantly higher in severe proteinuria patients compared to mild or no proteinuria. Salivary kappa levels were significantly higher in mild proteinuria patients compared to severe or no proteinuria. Salivary lambda levels decreased with increasing proteinuria severity. Serum kappa increase could be due to immune system activation and kidney compromise. Both serum and salivary kappa showed good predictive ability for post-surgery AKI prognosis compared to lambda and the kappa/lambda ratio, depending upon ROC performance. The study suggests FLCs, especially kappa, could be valuable in early AKI detection post-cardiac surgery, indicating potential for improved patient outcomes through proactive monitoring and intervention.

Background: Contrast-induced acute kidney injury (CIAKI) is a common complication in hospital-acquired renal conditions, yet its pathogenesis remains unclear and effective treatments are limited. Intermedin (IMD), a peptide related to the calcitonin gene, exhibits vasodilatory and endothelial barrier-stabilizing effects via the calcitonin receptor-like receptor (CLR). However, the potential of IMD in mitigating CIAKI has not been thoroughly investigated. Aims: This study aimed to delineate the protective role of IMD in CIAKI through both in vitro and in vivo models, with a particular focus on elucidating the underlying mechanisms, specifically the cAMP/Rac1 signaling pathway. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were evaluated using the CCK8 assay, flow cytometry, ELISA, and western blotting. A CIAKI rat model was developed to assess renal peritubular capillary endothelial cell injury and renal function using a range of techniques, including histopathology, immunohistochemistry, immunofluorescence, western blotting, and transmission electron microscopy. Results: In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway. The protective effects of IMD were attenuated by Rac1 inhibition. In vivo, CIAKI caused considerable damage to peritubular capillary endothelial cell junctions, leading to impaired renal function. IMD treatment markedly improved renal function, an effect that was abolished by Rac1 inhibition. Conclusion: IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, thereby preserving the integrity of peritubular capillary endothelial cells and mitigating acute renal injury induced by contrast media. These findings underscore the therapeutic potential of IMD in CIAKI and emphasize the critical role of the cAMP/Rac1 pathway in renal protection.

Identifying a panel of markers detecting kidney injury before the glomerular filtration rate (GFR) reduction is the challenge to improve the diagnosis and the management of acute kidney injury (AKI) in septic patients. This study evaluated the roles of tissue inhibitor metal proteinase, insulin growth factor binding protein (TIMP2*IGFBP7), and mid-regional pro-adrenomedullin (MR-proADM) in AKI patients. Patients and Methods: This study was prospectively conducted in the Intensive Care Unit (ICU) enrolling 230 patients who underwent cardiac surgery. Biomarkers were evaluated before and after 4 hours of the cardiac surgery. Results: Whereas urine and creatinine alterations appeared at 23.2 (12.7 – 36.5) hours, after cardiac surgery, urinary TIMP2*IGBP7 levels were higher at 4 hours in AKI patients (1.1±0.4 mg/l vs 0.08±0.02 mg/l; p < 0.001). Its concentration >2 mg/l increases the AKI risk within the following 24 hours, clearly identifying the population at high risk of renal replacement therapy (RRT). In patients with sepsis, MR-proADM levels were 2.3 nmol/l (0.7–7.8 nmol/l), with the highest values observed in septic shock [5.6 nmol/l (3.2–18 nmol/l)] and a better diagnostic profile than procalcitonin and C-reactive protein to identify septic patients. MR-proADM values >5.1 nmol/l and urine TIMP2*IGBP7 levels > 2 mg/l showed a significantly faster progression to RRT, with a mean follow-up time of 1.1 days. Conclusions: TIMP2*IGBP7 and MR-proADM precociously diagnose AKI in septic patients after cardiac surgery, giving prognostic information for RRT requirement.

Diarrhea is a common occurrence following vascular organ transplantation, including kidney transplants. It can be induced by non-infectious factors, adverse effects of immunosuppressive drugs, or infectious agents such as viruses, bacteria, fungi, or parasites. Intestinal protozoan parasites, include Cryptosporidium spp., are causes of infectious diarrhea particularly in immunocompromised patients. This review aims to summarize reports on epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in adult patients, particularly following kidney transplantation.

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption processes of large amounts of ultrafiltrate and dissolved substances. The place of action of oxidative stress is the influence on the balance in the production and breakdown of mitochondrial reactive oxygen species . A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future. The narrative review integrates results found in previously performed studies which have evaluated oxidative stress participation in renocardial syndrome type 3.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

Background and Objectives: The current study aimed to determine the impact of fasciotomy on mortality and morbidity in children and adults with crush-related AKI following the 2023 Kahramanmaraş earthquakes. Materials and Methods: The study included individuals who had suffered crush injuries after the 2023 Kahramanmaraş earthquakes and were identified as having acute kidney injury (AKI). Patients with AKI were divided into two groups based on age: those under 18 years and those over 18 years. A comparative analysis was conducted between the mortality and morbidity rates of patients who underwent fasciotomy and those who did not. Disseminated intravascular coagulopathy (DIC), sepsis, and adult respiratory distress syndrome (ARDS) have all been identified as contributors to morbidity. Results: The study was conducted with a total of 40 patients (21 males and 19 females) aged between four and 83 years. A total of 21 patients underwent fasciotomy and the patients underwent varying numbers of fasciotomy, ranging from zero to 11. The mortality rate was 12.5%, corresponding to five adult patients. No instances of mortality were reported in the paediatric cohort. The application of fasciotomy in instances of crush-induced AKI did not result in elevated levels of mortality in either the paediatric or adult demographic. Within the adult population, a substantial difference in the duration of dialysis was observed between individuals who underwent fasciotomy and those who did not. A statistically significant increase in the number of fasciotomy incisions was observed in patients diagnosed with sepsis compared with those without sepsis. The study found a significant positive correlation between the number of fasciotomy incisions and dialysis days. Conclusions: Neither adult nor paediatric patients with crush-induced AKI showed an increased risk of death after fasciotomy. The number of fasciotomy incisions significantly correlated with the development of sepsis. Despite experiencing delays in hospital admission for paediatric patients, the incidence of both crush syndrome and mortality rates among children remained relatively low.

AIM: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in gastrointestinal and hepatobiliary surgeries. Material and methods: All the gastrointestinal surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant Results: We performed 331 gastrointestinal and hepatobiliary surgery from April 2018 to March 2020. After exclusion 317 patients were included in study population.14 patients (4.4%) were defined as having acute kidney injury according to acute kidney injury network classifications. On univariate analysis acute kidney injury was associated with open surgery (p= 0.002, Intra operative hypotension (p=0.006), CDC grade of surgery (p<0.001), increased used to blood products (p=0.004), higher ASA grade (p<0.0001), increased operative time(p<0.0001). On multivariate logistic regression analysis higher ASA grade (p=0.001) and increased operative time (0.015) independently predicted acute kidney injury. Acute kidney injury was also significantly associated with 90 days mortality. ( p= <0.0001) Conclusion:Post-operative acute kidney injury was associated with significant mortality in gastrointestinal and hepatobiliary surgery. Open surgery, higher CDC grade surgery, more blood products, higher ASA grades, increase operative time predicted acute kidney injury in post operative periods. Higher ASA grades and increased operative time predicted acute kidney injury.

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with hypertension, but the mechanism by which it raises blood pressure is not understood. We hypothesize that exposure to Cd reduces the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73 m2 (low eGFR). The mean blood and urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. The prevalence odds ratio (POR) for hypertension rose twofold in those with blood Cd levels of 0.61-1.69 µg/L or urinary Cd excretion levels ≥ 0.98 µg/g creatinine. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in the normotensive group was 7.5 mL/min/1.73 m2 higher than the hypertensive with a similar Cd body burden. Mean systolic blood pressure (SBP) in those with low or medium eGFR plus heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. By mediation analysis, a 22.7% increase in SBP and a 5% increase in diastolic blood pressure (DBP) were attributable to the effect of Cd on GFR. Thus, a rise of blood pressure appears to be a consequence of GFR loss due to Cd-induced kidney damage. This finding is consistent with a well-known role of the kidney in long-term blood pressure regulation.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

Streptococcus pneumoniae is one of the associated bacteria that can cause the rare but high mortality hematological disease known as purpura fulminans (PF) in both adults and children. Patients with PF can progress quickly to sepsis and multiorgan failure, especially in immunocompromised individuals and young children. Due to the thrombotic blockage of blood arteries in PF, there is diffuse intravascular thrombosis and hemorrhagic infarction of the skin, which evolves from ecchymosis to skin necrosis, risk of limb sequelae, sepsis and fatality. We present a case of a previously healthy 1-year and 9-month female who was admitted to the Intensive Care Unit of the National Institute of Infectious Diseases "Prof. Dr. Matei Balș"- Bucharest, Romania. The patient presented with erythematous patches on left upper limb and trunk, tachycardia, tachypnea, hypotension, anuria and altered sensorium with an indication of intubation for 8 Glasgow Coma Scale (GCS). Cerebrospinal culture grew Streptococcus pneumoniae serotype 1. She required peritoneal dialysis due to acute kidney injury (AKI) and surgeries for affected areas. After multiple organ system failures, our patient evolved rapidly to irreversible tissue necrosis and death. We aim to report a rare case of PF associated with pneumococcal meningoencephalitis in immunocompetent children to better appreciate the risk of fatal evolution when managing this disease in children. To date, few studies report favourable evolution. We discuss the etiology, rapid diagnosis and treatment of immunocompetent children with PF and the importance of interprofessional teams to increase the outcomes in patients with infectious diseases.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the development and progression of multiple renal cysts, leading to progressive renal function decline. To date, the only approved treatment for this condition is able to slow down the loss of annual renal function, without stopping the disease progression. Furthermore, this therapy is approved only for patients with rapid disease progression and its compliance is problematic because of the impact of this drug on quality of life. The recent literature suggests that cystic cells are subject to metabolic dysregulation in the glucose pathway (Warburg Effect). This finding paved the way for new lines of research targeting potential therapeutic interventions for ADPKD. In particular, this review highlights the latest studies on the use of ketosis, through ketogenic dietary interventions (daily calorie restriction, intermittent fasting, time-restricted feeding, and ketogenic diets), as a potential strategy for patients with ADPKD, and the possible involvement of microbiota in the ketogenic interventions’ effect.

Acute kidney injury (AKI) is a frequent and critical complication in the clinical setting. In rodents AKI can be prevented effectively through caloric restriction (CR), which has also been shown to increase lifespan in many species. In Caenorhabditis elegans (C. elegans) longevity studies revealed that a marked CR-induced reduction of endocannabinoids may be a key mechanism. Thus, we hypothesized that regulation of endocannabinoids, in particular arachidonoyl ethanolamide (AEA), might also play a role in CR-mediated protection from renal ischemia-reperfusion injury (IRI) in mammals including humans. In male C57Bl6J mice, CR significantly reduced renal IRI and led to a significant decrease of AEA. Supplementation of AEA to near-normal serum concentrations by repetitive intraperitoneal administration in CR mice, however, did not abrogate the protective effect of CR. We also analyzed serum samples taken before and after CR from patients of three different pilot trials of dietary interventions. In contrast to mice and C. elegans, we detected an increase of AEA. We conclude that endocannabinoid levels in mice are modulated by CR, but CR-mediated renal protection does not depend on this effect. Moreover, our results indicate that modulation of endocannabinoids by CR in humans may differ fundamentally from the effects in animal models.

Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in KANK family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific Kank1 knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, Kank1 knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific Kank1 knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, KANK1-deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

Cellular senescence is the irreversible growth arrest subsequent to oncogenic mutations, DNA damage or metabolic insult. Senescence is associated with aging and chronic age associated diseases such as cardiovascular disease and diabetes. The involvement of cellular senescence in Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) is not fully understood however, recent studies suggest that such patients have a higher-than-normal level of cellular senescence and accelerated aging. This study aimed to discover key biomarkers of senescence in AKI and CKD patients compared to other chronic ageing diseases as controls. We show that senescence proteins CKAP4 and PTX3 are upregulated in AKI and CKD patients compared with controls with chronic diseases suggesting they may play in a role in overall kidney disease development. Additionally, CKAP4 was found to be differentially expressed in both AKI and CKD when compared to unhealthy controls hence this biomarker could be prognostic senescence biomarker of both AKI and CKD.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m²: 26.2% with eGFR 30-44 mL/min/1.73 m², 65.5% with eGFR 15-29 mL/min/1.73 m² and 8.3% with eGFR < 15 mL/min/1.73 m². Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p<0.001), NH weight (r=0.882, p<0.001), height (r=0.694, p<0.001), body mass index (BMI) (r=0.701, p<0.001), lean tissue mass (LTM) (r=0.664, p<0.001), lean tissue index (LTI) (r=0.433, p<0.001), fat mass (r=0.614, p<0.001) and fat tissue index (FTI) (r=0.449, p<0.001), and was negatively associated with clinical variable such as hydration status (p<0.001). HGS significantly and positively correlated with anthropometric parameters such as body mass (r=0.319, p=0.003), NH weight (r=0.315, p=0.004), height (r=0.666, p<0.001), LTM (r=0.490, p<0.001), LTI (r=0.238, p=0.029), and ASM (r=0.501, p<0.001), and was negatively associated with clinical variables like uric acid (p=0.039) and urea (p<0.001). After adjustment for age, sex and height, HGS remained significantly and negatively related with uric acid (β=-1.078, p=0.041) and hydration status (β=-0.805, p=0.042). Conclusions In CKD patients, ASM is determined mainly by anthropometric parameters but HGS - both by anthropometric and clinical variables specific for CKD.

Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

Fever control is essential in patients with severe traumatic brain injury (TBI). The efficacy of therapeutic hypothermia (TH) in severe TBI has been investigated over the last few decades; however, in contrast to experimental studies showing benefits, no evidence of efficacy has been demonstrated in clinical practice. In this review, the mechanisms and history of hypothermia were briefly outlined, while the results of major randomized controlled trials (RCTs) and meta-analyses investigating TH for adult TBI are introduced and discussed. The retrieved meta-analyses showed conflicting results, with a limited number of studies indicating benefits of TH. Some studies have shown benefits of long-term TH compared with short-term TH. Although TH is effective at lowering elevated intracranial pressure (ICP), reduced ICP does not lead to favorable outcomes. Low-quality RCTs overestimated the benefits of TH, while high-quality RCTs showed no difference or worse outcomes with TH. RCTs assessing standardized TH quality demonstrated the benefits of TH. As TBI has heterogeneous and complicated pathologies, applying a uniform treatment may not be ideal. A meta-analysis of young patients who underwent early cooling and hematoma removal showed better TH results. TH should not be abandoned, and its optimal should be advocated on an individual basis.

Objective: To report time-loss match injuries in Portugal’s “Divisão de Honra” (Portuguese First Tier) 2022/23 season focusing on injury incidence, injury burden, anatomical region and type of injury. Methods: A cohort prospective observational study was conducted. Data was collected through an online form sent for every team medical department categorizing player position, injury type, location and severity. Injury incidence and burden were calculated per 1000-player-match-hours. Results: The overall injury incidence was 54.4 injuries per 1000 player-match-hours (CI95% 30.3-96.2). Forwards had a higher incidence comparing to backs. Lower limbs were the most affected location (52% of the injuries). Sprain/ligaments injuries were the most common type of injury followed by muscle injuries. Discussion: The injury incidence was higher than what is reported in amateur competitions and lower than professional ones. Injury severity was similar to other studies. Our study suggests a lower injury burden compared to other semi-professional and elite leagues. Further research with broader participation and training injury data is needed.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Background. National surveys reported on variable prevalence of chronic kidney disease (CKD) due to differences in characteristics of population, design, equations used to estimate glomerular filtration rate (eGFR) and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence and cardio-kidney-metabolic risk factors in Croatia which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of albumin-to-creatinine ratio (ACR) and eGFR (CKD EPI equation). Comorbidities, anthropometric and social factors related to the prevalence of CKD were analyzed, and CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥ G3A A2, and CKD defined only as eGFR < 60 ml/min/1.73 m2 were estimated at 17.1%, 9.8% and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p 30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD of 9.5%. Unaware were older with lower income, less educated, having more frequently diabetes, hypertension (less frequently controlled) and milder renal impairment. Conclusion. In Croatia, the estimated prevalence of CKD is high, being more frequently presented in men than in women. CKD patients have unfavorable CV risk profile. The awareness of CKD is very low reflecting poor health literacy in general population but also in health care workers.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

Electrolyte disturbances are common in patients with traumatic brain injury (TBI), particularly affecting sodium, potassium, chloride and calcium levels. This study aims to provide insights into these disturbances within the first 24 hours post-injury. We conducted a cross-sectional analysis of 50 TBI patients, excluding those with conditions affecting electrolyte balance. Electrolyte levels were measured, and correlations with demographic data, trauma mechanisms, imaging findings, and Glasgow Coma Scale (GCS) scores were analyzed. Results indicated that chloride levels inversely correlated with GCS scores (ρ = -0.515; p = 0.002), suggesting that elevated chloride may indicate severe neurological impairment. Potassium levels were significantly associated with subdural hematoma (p = 0.032) and subarachnoid hemorrhage (p = 0.043), highlighting their potential as markers for severe brain injuries. No significant associations were found between sodium or calcium levels and the studied variables. These findings underscore the importance of early monitoring of chloride and potassium levels in TBI patients to improve management and outcomes. Future research should focus on larger, multi-center studies to validate these findings and develop comprehensive guidelines for managing electrolyte imbalances in TBI patients.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

Statistical data extracted from national databases demonstrate a continuous growth in the incidence and prevalence of chronic kidney disease (CKD) and the ineffectiveness of current policies and strategies based on individual risk factors to reduce them, as well as their mortality and costs. Some innovative programs, telemedicine and government interest in the prevention of CKD, did not facilitate timely access to care, continuing the increased demand for dialysis and transplants, high morbidity and long-term disability. In contrast, new forms of kidney disease of unknown etiology affected populations in developing countries and underrepresented minorities, who face socioeconomic and cultural disadvantages. With this background, we analyze in the existing literature the effects of social determinants in CKD, concluding that it is necessary to strengthen current kidney health strategies, designing in a transdisciplinary way, a model that considers demographic characteristics integrated into individual risk factors and risk factors population, incorporating the population health perspective in public health policies to improve results in kidney health care, since CKD continues to be an important and growing contributor to chronic diseases.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions that can lead to the loss of structure and/or function impairment. These changes can cause a partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, what in turn can affect the quality of life. For those reasons, PNI is a major public health concern. This review aims to revisit the concepts associated with the PNI. First, the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to explain the urge for new approaches and to understand the methods to evaluate nerve regeneration in a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.

The main characteristic of polycystic kidney disease is the development of multiple fluid filled renal cysts. The discovery of mislocated Na,K-ATPase in the apical membrane of cyst lining epithelia alluded to a reversal of polarity as a possible explanation to the fluid secretion. The topic of apical Na,K-ATPase in cysts remains controversial. We investigated the localization of the Na,K-ATPase and assessed the apical-basolateral polarization of cyst lining epithelia by means of immunohistochemistry in kidney tissue from six polycystic kidney disease patients undergoing nephrectomy. The Na,K-ATPase α1 subunit was conventionally situated in the basolateral membrane of all immunoreactive cysts. Proteins of the Crumbs and partitioning defective (Par) complexes were localized to the apical membrane domain in cyst epithelial cells. The apical t-SNARE protein Syntaxin-3 also immunolocalized to the apical domain of cyst lining epithelial cells. Proteins of the basolateral Scribble complex immunolocalized to the basolateral domain of cysts. Furthermore, we confirmed that cysts can originate from virtually any tubular segment with preserved polarity. In conclusion, we find no evidence of a reversal in apical-basolateral polarity in cyst lining epithelia in polycystic kidney disease.

Background/Objectives: Caregivers play an important role in supporting care recipients to navigate their health needs including adherence to dietary recommendations which are complex and multifaceted. The study aimed to i) describe the nutrition knowledge of caregivers of people with chronic kidney disease (CKD), and ii) explore caregivers’ perception of their role in providing healthy meals and nutrition support for care recipients. Methods: Caregivers (n=78) of people with stage 1-5 CKD or post-transplant were recruited from a single centre. A sequential mixed-methods approach was used. Nutrition knowledge was assessed with the revised General Nutrition Knowledge questionnaire. Theory informed semi-structured interviews in a sub-sample (n=12) explored caregiver perception. Results: Most caregivers were female (75.6%) caring for a male care recipient (87%; aged 74 (66;80) yrs.). Caregivers (75.6%) provided a meal ≥6 times/week to their care recipient and had moderate nutrition knowledge (66.1 (60.5; 73.9) %). Four themes emerged describing caregivers’ perception on meal provision and nutrition support including i) food literacy skills are valued, ii) social support is important, iii) caregivers’ sense of social responsibility, and iv) meal provision is complex and dynamic. Conclusions: Caregivers have moderate nutrition knowledge; they want to provide healthy meals and support to care recipients to adhere to dietary recommendations. Targeted, co-designed nutrition education programs for caregivers may enhance nutrition care delivery to people with CKD.

Patients with chronic kidney disease (CKD), particularly those with end-stage kidney disease (ESKD) undergoing dialysis or kidney transplantation, face ongoing challenges in relation to the risk of COVID-19. In addition to their underlying condition, factors such as immune-evasive variants, immunosuppressive therapies, and the need for dialysis contribute to poor COVID-19 outcomes in this population. Severe COVID-19 can lead to the deterioration of CKD/ESKD, resulting in acute kidney injury, septic shock, and respiratory failure. Moreover, patients with CKD/ESKD have shown impaired response to COVID-19 vaccination, with seroconversion failures associated with the burden of immunosuppressive treatments, further heightening their vulnerability to severe disease. Despite the current endemic, it is crucial to acknowledge the ongoing significance of COVID-19 as a serious threat to patients burdened with chronic diseases like CKD and ESRD. Understanding the impact of COVID-19 on these patients is essential, as they remain at risk of severe disease progression. This paper presents the results of a literature review to enhance our understanding of COVID-19-related risks in patients with CKD/ESKD. Expert insights and illustrative scenarios provide practical perspectives and highlight the importance of risk stratification based on clinical factors for guiding targeted measures and treatments to mitigate COVID-19 risks in these vulnerable patients.

Background: Injury of the spinal cord causes motor and sensory dysfunction, and pathological reflexes, leading to paraplegia or tetraplegia. The sequelae of traumatic spinal cord injury (SCI) is a significant burden and impact on healthcare systems. Despite constant progress in medicine, traumatic SCI still remains irreversible. Till now, no satisfying treatment that can enable neuronal regeneration and recovery of function at the damaged level has been found. Hundreds of experiments have been conducted on various possibilities of influencing spinal regeneration, some of them have yielded promising results, but unfortunately, the successes obtained in experimental animals have not translated into humans. Methods: This narrative review article presents the application of Extracorporeal Shock Wave Therapy (eSWT) in Spinal Cord Injury. The article has been divided into parts: 1. Use of extracorporeal Shock Wave Therapy for regeneration of the spinal cord after traumatic Spinal Cord Injury. 2. Application of extracorporeal Shock Wave Therapy in spasticity after Spinal Cord Injury. In both cases, the hypotheses of possible mechanisms of action will be described. Results and conclusions: A small number of clinical trials have demonstrated the potential of eSWT to influence the regeneration of the spine, as an innovative, safe, and cost-effective treatment option for patients with SCI. Some reports have shown that eSWT can improve spasticity, walking ability, urological function, quality of life, and independence in daily life.

The incidence of diabetes mellitus (DM) continues to rise worldwide and one of the most serious microvascular complications is diabetic kidney disease (DKD), which is the leading cause of end-stage renal disease. Current bi-omarkers such as urinary albumin excretion rate have limitation for early detection of DKD. In our study we used ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-ESI+-MS) techniques to quantify previously analyzed metabolites, such as tryptophan, kynurenic acid, taurine, l-acetylcarnitine, glycine, and tiglylglycine. We performed the targeted analy-sis of metabolites from urine and serum samples, collected from 110 subjects. Of these, 90 patients with type 2 DM (T2DM) were divided according to the urinary albumin/creatinine ratio (UACR) into normoalbuminuria 300 mg/g groups, respectively, while 20 subjects were rep-resented by healthy controls. Through various validation methods, we identified several metabolites as potential biomarkers, such as kynurenic acid, glycine, and l-tryptophan in serum and l-acetylcarnitine, tiglylglycine, and tau-rine in urine.

BACKGROUND: Lower limb skeletal muscle ischemia-reperfusion (IR) injury associated with increased morbidity and mortality is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. METHODS: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups of six each. (Group Control-C, Group Ischemia-Reperfusion -IR, Group Ischemia-Reperfusion and Proanthocyanidin-IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 minutes before laparotomy and 1-hour ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. RESULTS: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than group control and group IR-proanthocyanidin. Besides, oval-central nucleus standardization was significantly higher in the IR and proanthocyanidin group than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-proanthocyanidin groups while, catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR and proanthocyanidin groups. CONCLUSION: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Objective: Lower extremity ischemia-reperfusion injury (IRI) may occur with trauma-related vascular injury and various vascular diseases, during the use of a tourniquet, temporary clamping of the aorta in aortic surgery, and acute or bilateral acute femoral artery occlusion. Mitochondrial dysfunction and increased basal oxidative stress in diabetes may cause an increase in the effects of increased reactive oxygen species (ROS) and mitochondrial dysfunction due to IRI. It is of great importance to examine therapeutic approaches that can minimize the effects of IRI, especially for patient groups under chronic oxidative stress. Cerium oxide (CeO2) nanoparticles mimic the antioxidant enzymes and act as a catalyst that scavenges ROS. In this study, it was aimed to investigate whether CeO2 has protective effects on skeletal muscles in lower extremity IRI in mice with streptozocin-induced diabetes. Methods: A total of 38 Swiss albino mice were divided into six groups as follows: control group (group C, n=6), diabetes group (group D, n=8), diabetes-CeO2 (group DCO, n=8), diabetes-ischemia/reperfusion (group DIR, n=8), and diabetes-ischemia/reperfusion-CeO2 (group DIRCO, n=8). DCO and DIRCO groups were given doses of CeO2 0.5mg/kg intraperitoneally 30 minutes before the IR procedure. A 120-minute ischemia-120-minute reperfusion period with 100% O2 was performed. At the end of the reperfusion period, muscle tissues were removed for histopathological and biochemical examinations. Results: Total antioxidant status (TAS) levels were found to be significantly lower in group DIR compared with group D (p=0.047 and p=0.022, respectively). In group DIRCO and total oxidant status (TOS) levels were found to be significantly higher than in group DIR (p

Traumatic Brain Injury (TBI) is one of the leading causes of death and disability worldwide. Patient treatment and management pose a challenge for healthcare systems. The prognosis of these patients may be influenced by factors such as sex. This study aims to describe the clinical parameters of patients hospitalized in the Intensive Care Unit (ICU) of a Spanish hospital due to Trauma Brain Injury and to establish differences based on sex. Methodology: An observational, cross-sectional, and analytical study was conducted from March 2015 to December 2019. All patients admitted to the ICU during this period who presented isolated significant Traumatic Brain Injury, defined as an abbreviated injury scale (AIS) ≥ 3, were included. Data on baseline characteristics, mechanism of injury, substance use, and acute management in the prehospital and hospital stages (including the need for hospitalization) were recorded. A descriptive and in-ferential analysis was conducted using the chi-square test. Results: A total of 950 patients were ultimately included. The majority of the patients were men (723) with a mean age of 45.16 (± 17.55). There were statistically significant differences in terms of the mechanism of injury (p

Background: Ventilatory strategies in acute respiratory distress syndrome patients aim to mitigate the risk of acute lung injury (ALI). However, prolonged utilization of these strategies may precipitate alveolar carbon dioxide elevation and pH reduction. This scoping review endeavors to present extant knowledge concerning hypercapnia effects in experimental models, with or without ALI, specifically focusing on delineating the immunologically mediated pulmonary tissue damage; Methods: A systematic exploration encompassing PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and Scielo databases was undertaken. Articles published between January 1, 2008, and December 31, 2022, were screened for their elucidation of hypercapnia's immunological impact on lung tissue, utilizing experimental or biological models, irrespective of ALI presence; Results: Following duplicate removal and predefined criteria filtering, 30 pertinent articles scrutinizing hypercapnia's influence on pulmonary epithelium were identified. It was observed that hypercapnia induces perturbations in innate immune response gene transcription, mediated via Nuclear Factor-kappa B attenuation. Furthermore, a compromised innate immune response against injurious agents was noted. Concurrently, disruption and subsequent resealing of alveolar epithelial cells were evidenced, primarily through Na/K-ATPase endocytosis, impeding fluid reabsorption at the alveolar epithelium level; Conclusions: In experimental settings, with or without ALI, hypercapnia's immunomediated mechanisms exacerbate innate immune system impairment and disrupt the respiratory epithelium's repair and healing processes.

Traumatic brain injury (TBI) is an important global clinical issue, requiring not only prevention but also effective treatment. Following TBI, diverse parallel and intertwined pathological mechanisms affecting biochemical, neurochemical, and inflammatory pathways can have severe impact on the patient’s quality of life. The current review summarizes evidence for utility of amantadine in TBI in connection to its mechanism of action. Amantadine combining multiple mechanisms of action may offer both neuroprotective and neuroactivating effects in TBI patients. Indeed, use of amantadine in TBI has been encouraged by several clinical practice guidelines/recommendations. Amantadine is also available as infusion which may be of particular benefit in unconscious patients with TBI, due to immediate delivery to the central nervous system and the possibility of precise dosing. In other situations, orally administered amantadine may be used. There are several questions that remain to be addressed: Can amantadine be effective in disorders of consciousness requiring long-term treatment and in combination with drugs approved for treatment of TBI? Do the observed beneficial effects of amantadine extend to disorders of consciousness due to factors other than TBI? Well controlled clinical studies are warranted to ultimately confirm its utility in the TBI and provide answers these questions.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

Kidney diseases are worldwide public health problems affecting millions of people. However, there are still limited therapeutic options against kidney diseases. Semaphorin 3A (SEMA3A) is the secreted and membrane-associated proteins, which regulate diverse functions, including immune regulation, cell survival, migration and angiogenesis, thus involving in the several pathogeneses of diseases, including eyes and neurons, as well as kidneys. SEMA3A is expressed in podocytes and tubular cells in the normal adult kidney, and recent evidence revealed that excess SEMA3A expression and subsequent signaling pathway aggravates kidney injury in a variety of kidney diseases, including nephrotic syndrome, diabetic nephropathy, acute kidney injury, and chronic kidney disease. In addition, several reports demonstrated that inhibition of SEMA3A ameliorated kidney injury via reduction of cell apoptosis, fibrosis and inflammation, thus SE-MA3A may be a potential therapeutic target for kidney diseases. In this review article, we summarized current knowledges regarding the role of SEMA3A signaling in kidney pathophysiology and their potential use in kidney diseases.

Commonly macrophages are categorized into M1 and M2 subsets. M1 macrophages are defined as inflammatory cells and may contribute to tissue injury, while, M2 macrophages play a central role in tissue remodeling and control of immune responses. It seems that the existence of these cells in graft location is effective for control of inflammation and improvement of transplantation consequences. Although the relative contribution of M2 cells in organ transplantation is not clear, the accumulation of these cells in acute and chronic injury models of transplantation was shown. In some cases, the depletion of M2 cells leads to the amelioration of disease; however in other causes, skewing the response in M2 cells leads to an augmentation of graft fibrosis and worsening of graft condition. In spite of these findings, the benefits of such strategies and their implications in human disease are not clearly understood. The purpose of this mini-review is to highlight the role of alternatively activated M2-type macrophages in the improvement or reduction of the kidney transplantation outcome.

The present review aimed to identify through what means neurologic injury can predispose individuals to Post-Traumatic Stress Disorder (PTSD). In recent years, comprehensive studies have helped to clarify which structures in the central nervous system (CNS) that, when damaged, lead to distinct PTSD symptoms–namely dissociative reactions or flashbacks. Our review narrowed its focus to three common neurologic injuries including traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and stroke. Beyond discussing the potential mechanisms by which neurotrauma may lead to PTSD, we summarized our current understanding of the pathophysiology of the disorder and discussed predicted associations between the limbic system and PTSD. In particular, the role of noradrenergic neuromodulatory signaling on the HPA axis as it pertains to fear memory recall needs to be further explored to better understand its effects on limbic structures in PTSD patients. This paper also described how damage to the CNS can alter the function of the limbic system and result in characteristic symptoms of PTSD like intrusive memories and acute psychological distress. Further, our review intended to draw attention to a lack of PTSD prognosis in TBI, SAH, and stroke patients who could benefit from early treatment. PTSD symptoms often compound with pre-existing issues further deteriorating health outcomes for these patients. It is ultimately our goal to clarify the relationship between neurotrauma and PTSD such that earlier diagnoses and appropriate treatment are observed in clinic.

Abstract Precision medicine is essentially based on reliable and non-invasive biomarkers. Aim of this review has been to describe the newest biomarkers in the field of kidney transplantation and the kidney rejection, one of the commonest and severe complications. Standard of care tools to identify acute rejection are largely full of errors and of drawbacks. In recent years new and reliable biomarkers have been found. They are avoid of risks, non-invasive and able to detect rejection even in those frequent cases in which acute rejection are clinically asymptomatic and not otherwise identifiable. In recent years several biomarkers have been identified. Very recently have been found new relevant biomarkers able to diagnose rejection with high positive predictive value and low negative predictive value. These are the donor derived cell free DNA found in the recipient, the gene expression profile of the donor found in the recipient and the urinary cytokines that express modification in the graft tissue. The aim of this study has been to find the most recent findings in the literature on this topic and to describe the utility and possible limitation of such new biomarkers on kidney rejection.

Microbiota-based strategies are a novel auxiliary therapeutic and preventative way of moderating chronic kidney disease. Lactobacillus mixture (Lm) was previously demonstrated to exert a renal-protective function in the CKD mice model. The efficacy of probiotics in pet foods is a relatively new area of study, and thus verifying the potential health benefits is necessary. This study evaluated the efficacy of Lm treats in feline CKD and elucidated the mechanisms underlying host-microbe interactions. CKD cats (2 and 3 stages) were administrated probiotic pet treats daily (10 g) for 8 weeks. The results demonstrated that during the eight weeks of Lm administration, creatinine was reduced or maintained in all cats with CKD. Similarly, gut-derived uremic toxins (GDUT), IS, and TMAO were significantly downregulated in the serum (confidence intervals = 90%). The life quality of the cats also improved. Feline gut microbiome data, KEGG pathway, and renal function indicator analyses revealed the possible mechanisms involved in modulating CKD feline microbial composition. Further regulation of the microbial functions in amino acid metabolism after Lm administration contributed to downregulating deleterious IS, PCS, and TMAO. The current study provides potential adjuvant therapeutic insights into probiotic pet foods or treats for pets with CKD.

Creatine has been linked to the development of kidney damage since 1998. However, uncertainties persist regarding the actual impact of creatine supplementation on individuals with kidney disease before supplementation or with pathological conditions that have an increased risk of developing kidney dysfunction. This study performed a comprehensive review of the literature and utilized bioinformatics tools to investigate the effects of creatine on renal tissue and function. Moreover, we identified 44 genes modulated explicitly in response to creatine exposure using the Comparative Toxicogenomics Database, including IGF1, SLC2A4, and various creatine kinase genes. The analysis revealed associations with metabolic processes such as amino acid metabolism, indicating a connection between creatine and tissue physiology. Gene expression analysis using the Genotype-Tissue Expression Portal highlighted tissue-specific expression patterns in kidney and pancreas tissues. Furthermore, the study explored creatine metabolism pathways and kinase regulation through biological databases and Gene Expression Omnibus data, shedding light on the potential regulatory roles of creatine in cellular processes during kidney diseases. Understanding the impact of the balance between the endogenous creatine synthesis and the creatine uptake, particularly the genes GATM, GAMT, SLC6A8 and IGF1, insights into molecular mechanisms underlying creatine's physiological effects on renal tissues. Overall, this work provides new insights into the molecular interactions and pathways influenced by creatine in renal function.

Introduction: Glomerulopathy is a term used to describe a broad spectrum of renal diseases, character-ized by dysfunction of glomerular filtration barrier, especially of podocytes. Several podocyte-associated proteins have been found and proved their usefulness as urine markers of podocyte dysfunction. Two of them are nephrin (NEP) and prodocalyxin (PDC). Purpose: This study aims to evaluate the association of podocyte damage, as it is demonstrated via the concentrations of urinary proteins, with clinical and histological data from patients with several types of glomerulonephritis. Methods: We measured urine levels of two podocyte-specific markers, NEP and PDC (corrected for urine creatinine levels), in patients with a wide range of glomerulopathies. Serum and urine parameters as well as histological parameters from renal biopsy were recorded. Results: In total, data from 37 patients with glomerulonephritis and 5 healthy controls were analyzed. PDC and NEP concentrations correlated between them and with serum creatinine levels (p=0.001 and p=0.013 respectively), and with histological lesions associated with chronicity index of renal cortex, such as severe interstitial fibrosis, severe tubular atrophy and hyalinosis (for PDC/NEP, all p3gr/24h with diffuse fusion of podocyte foot processes (p=0.016) was identified. Conclusions: Podocalyxin and nephrin concentrations in urine represent markers of podocyte dysfunction and in our study they were associated both with serum creatinine and histological chronicity indices.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

In December 2019, an animal human coronavirus transmission occurred in Wuhan, China. A state of global pandemic was shortly declared, among a very rapid contagious spread of the virus. The causative virus was identified as SARS CoV 2 virus and is genetically related to the previous SARS outbreak in 2003. The virus causes wide clinical spectrum from mild flu like symptoms to adult respiratory distress syndrome. Kidney involvement has been reported in several reports in patients with various degrees of severity of SARS CoV2 infection. As knowledge is evolving, the accurate incidence of AKI is not known. Many questions are yet to be answered as regards the effect of epidemiological variables and comorbidities on the occurrence of AKI. Some reports have observed the occurrence of hematuria and proteinuria in a percentage of infected patients. Moreover, chronic kidney disease has not been found in some reports to add to the adverse outcomes, an aspect that merits further exploration. Patients on regular hemodialysis may be vulnerable to contagion due to lower status of immunity and need for frequent attendance to healthcare facilities. Due to the previous factors, prevention and mitigation of SARS CoV2 virus in this vulnerable population constitutes a major challenge.

Background and Aim: It is generally accepted that oxidative stress mediators play an important role in ischemia-reperfusion injury(I/R), although the exact mechanism is not fully elucidated. While the impact of silymarin on I/R injury in several tissues, including the myocardial, cerebral, gastric and liver tissue, has been examined, the present state of research on this topic remains insufficient to provide a widely accepted understanding. For this purpose, our objective was to examine the effect of silymarin on muscle tissue in rats subjected to lower extremity I/R injury. Method: After ethics committee approval, 18 male Wistar albino rats weighing between 225-275 g were used. The rats were divided into three groups containing six mice each, Control,Ischemia-Reperfusion and Silymarin-Ischemia/Reperfusion groups. Silymarin was administered intraperitoneally 30 minutes before the procedure.( 100 mg/kg-1 ) In the I/R groups, an atraumatic microvascular clamp was placed in the infrarenal abdominal aorta. After 120 minutes, the clamp was removed and reperfusion was achieved for 120 minutes. In muscle tissue samples taken at the end of the reperfusion period; Malondialdehyde (MDA) levels, catalase (CAT) enzyme activity levels and histopathological parameters were compared. Results: In the histopathological examination, no degeneration was observed in the muscle fibers in the control group, while findings of striated muscle damage such as muscle atrophy hypertrophy, muscle degeneration-congestion, internal of the muscle nucleus-oval-central nucleus, fragmentation-hyalinization and leukocyte cell infiltration were observed in the I/R group. In the S-I/R group, muscle atrophy hypertrophy, internal of the muscle nucleus-oval-central nucleus, fragmentation-hyalinization and leukocyte cell infiltration were observed to improve these damaged areas compared to the I/R group. MDA levels in the I/R group were found to be significantly higher than in the control and S-I/R groups. CAT enzyme activity was found to be significantly higher in the I/R group than in the control group. Conclusion:Our study revealed that the administration of silymarin at a dosage of 100 mg/kg-1 by intraperitoneal injection 30 minutes before ischemia in rats effectively decreased lipid peroxidation and oxidative stress. Additionally, it successfully reduced the injury caused by ischemia/reperfusion in muscle histology.

Background/Objectives: Patients with chronic kidney disease (CKD) have an increased risk of cardiovascular disease (CVD). Carotid intima-media thickness (C-IMT) is a non-invasive marker of atherosclerosis. Low omega-3 polyunsaturated fatty acids (PUFA) intake and vitamin D deficiency are potential cardiometabolic risk factors in patients with CKD. The aim of this study was to evaluate dietary intake and status of omega-3 PUFA and vitamin D in pre-dialysis and hemodialysis patients and to examine the link of dietary α-linolenic acid (ALA) and fish consumption with blood pressure and C-IMT in CKD patients. Methods: All 77 selected patients (36 pre-dialysis, 41 on hemodialysis) underwent standardized clinical, nutritional, and laboratory assessments. Repeated 24-hour recalls were performed to assess dietary intake. The fatty acid profile was determined by gas-liquid chromatography. Results: Inadequate vitamin D intake and vitamin D status were found in 95% of patients. PUFAs profiles did not differ between hemodialysis and pre-dialysis participants. Dietary intake of ALA was negatively correlated with systolic blood pressure (SBP) (p=0.007), C-IMT (p=0.002), serum CRP (p=0.044), iPTH (p=0.01) and 25(OH)D3 (p=0.006). ALA intake of more than 0.23 g/daily was associated with lower SBP (p=0.001), serum 25(OH)D3 (p=0.004), and C-IMT (p=0.002). Conclusions: This study contributes to a better understanding of the relationship between dietary ALA intake and C-IMT in CKD. The results of this study could emphasize the significant role of the high prevalence of vitamin D deficiency and inadequate omega-3 PUFA intake and status considering CVD health in CKD patients.

Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

Embryonic genetic mechanisms are present in the brain and ready to be placed into action upon cellular injury termed the response to injury wound healing (RTIWH) mechanism. When injured, regional brain endothelial cells initially undergo activation and dysfunction with initiation of hemostasis, inflammation (peripheral leukocytes and innate microglia and perivascular macrophage cells), proliferation (astrogliosis), remodeling, repair, and resolution phases if the injurious stimuli are removed. In conditions wherein the injurious stimuli are chronic as occurs in obesity, metabolic syndrome, and type 2 diabetes mellitus this process does not undergo resolution and there is persistent RTIWH with remodeling. Indeed, the brain is unique, in that it utilizes its neuroglia: the microglia cell along with peripheral inflammatory cells and its astroglia instead of peripheral scar-forming fibrocytes/fibroblasts. The brain undergoes astrogliosis to form a gliosis scar instead of a fibrosis scar to protect the surrounding neuropil from regional parenchymal injury. One of the unique and evolving remodeling changes in the brain is the development of enlarged perivascular spaces (EPVS), which is the focus of this brief review. EPVS are important since they serve as a biomarker for cerebral small vessel disease and also represent an impairment of the effluxing glymphatic system that is important for the clearance of metabolic waste from the interstitial fluid to the cerebrospinal fluid and disposal. Therefore, it is important to better understand how the RTIWH mechanism is involved in the development of EPVS that are closely associated with and important to the development of premature and age-related cerebrovascular and neurodegenerative diseases with impaired cognition.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites between A-56 and A-75, and (ii) major C-terminal cleavage sites between T-383 and Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78, R-79, D-266 and A-267, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

Area covered: These drugs, particularly calcineurin inhibitors, have very narrow therapeutic windows, i.e., they have numerous drug-related side effects. Herein, we focus on the most frequent immunosuppressive drug-related side effects that we encounter in kidney-transplant recipients: namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). However, other therapies that are used after kidney transplantation, e.g., valcancyclovir, may also contribute to adverse events such as leukopenia. For each side-effect, we suggest how it can be prevented and how to treat it when present.

Zinc (Zn) is the second most abundant metal in the human body, and is essential for the function of 10% of all proteins. As metals cannot be synthesized or degraded, they must be assimilated from diet by specialized transport proteins, which unfortunately also provide an entry route for the toxic metal pollutant cadmium (Cd). The intestinal absorption of Zn depends on the composition of food that is consumed, firstly the amount of Zn itself, and then the quantity of other food constituents such as phytate, protein and calcium (Ca). In cells, Zn is involved in regulation of intermediary metabolism, gene expression, cell growth, differentiation, apoptosis, and antioxidant defense mechanisms. Cellular influx, efflux, subcellular compartmentalization, and trafficking of Zn are coordinated by transporter proteins, the Solute-Linked Carrier 30A and 39A (SLC30A and SLC39A), known as the ZnT and the Zrt-/Irt-like protein (ZIP). Because of its chemical similarity with Zn and Ca, Cd disrupts the physiological functions of both. The concurrent induction of a Zn efflux transporter ZnT1 (SLC30A1) and metallothionein by Cd disrupts the homeostasis and reduces the bioavailability of Zn. The present review highlights the increased mortality and the severity of various diseases, including those induced by COVID-19 infections, among Cd-exposed persons and the roles of Zn and other transport proteins in the manifestation of Cd cytotoxicity. Special emphasis is given to the potential protective effects of Zn against bone, lung and heart diseases associated with Cd exposure. The difficult challenge of determining a permissible intake level of Cd is discussed in relation to the recommended dietary Zn intake levels.

(1) Background: Multiple alterations of cellular metabolism have been documented in experimental studies of autosomal dominant polycystic kidney disease (ADPKD) and are thought to contribute to its pathogenesis. (2) Methods: To elucidate the molecular pathways and transcriptional regulators associated with the metabolic changes of renal cysts in ADPKD, we compared global gene expression data from human PKD1 renal cysts, minimally cystic tissues (MCT) from the same patients, and healthy human kidney cortical tissue samples. (3) Results: We found PKD1 renal cysts displayed the Warburg effect with gene pathway changes favoring increased cellular glucose uptake and lactate production, instead of pyruvate oxidation. Additionally, mitochondrial energy metabolism was globally depressed, associated with downregulation of gene pathways related to fatty acid oxidation (FAO), branched-chain amino acid (BCAA) degradation, the Krebs cycle, and oxidative phosphorylation (OXPHOS) in renal cysts. Activation of mTORC1 and its two target proto-oncogenes, HIF-1α and MYC, was predicted to drive the expression of multiple genes involved in the observed metabolic reprogramming (e.g., GLUT3, HK1/HK2, ALDOA, ENO2, PKM, LDHA/LDHB, MCT4, PDHA1, PDK1/3, MPC1/2, CPT2, BCAT1, NAMPT); indeed, their predicted expression patterns were confirmed by our data. Conversely, we found AMPK inhibition was predicted in renal cysts. AMPK inhibition was associated with decreased expression of PGC-1α, a transcriptional coactivator for transcription factors PPARα, ERRα, and ERRγ, all of which play a critical role in regulating oxidative metabolism and mitochondrial biogenesis. (4) Conclusions: These data provide a comprehensive map of metabolic pathway reprogramming in ADPKD and highlight nodes of regulation that may serve as targets for therapeutic intervention.

Introduction: The COVID-19 pandemic challenged people with spinal cord injury (SCI) regarding a variety of mental and physical issues. New challenges may arise as the effects of the pandemic continue. The objective of the present study was to explore the social participation of Canadians with SCI during the second wave of COVID-19. Methods: Participants with SCI from two Canadian provinces (Quebec and British Columbia) were interviewed. Results: Eighteen participants completed interviews. Facilitators of social participation remain similar since the first wave of COVID-19, such as the use of technology, help received by relatives and the use of delivery services to obtain groceries and other essentials. Obstacles to mobility due to winter conditions and lack of considerations related to COVID-19 public health measures specific to wheelchair users were also discussed by participants. Conclusions: People with SCI perceived participation restrictions, little changes in life habits, and uncertainty about the future during the second wave of COVID-19. The unique living conditions of people with SCI, ability to adapt life habits, and the lived experiences of people with SCI may have contributed to an overall resilience during the pandemic. Adaptive families, social contacts and technology made a difference during the pandemic.

Capsinoids (CAP) are potential antioxidant agents capable of reducing oxidative damage and the resulting complications triggered by obesity. Thus, the aim of this study was to investigate the effects of CAP on adiposity and biomarkers of cardiac oxidative stress in rats with obesity induced by a high-fat diet. Male Wistar rats were exposed to a high-fat diet for 27 consecutive weeks. After characterization of obesity (week 19), some of the obese (Ob) animals began to receive capsinoids (10 mg/kg/day) by orogastric gavage. Adiposity and comorbidities were assessed. In the heart, remodeling, injury and biomarkers of oxidative stress were determinated. The treatment did not reduce the adiposity induced d by obesity, but they were efficient in reducing cholesterol levels. CAP treatment did not cause a difference in heart and LV mass, despite having reduced troponin I concentrations. Furthermore, capisinoids did not reduce the increase in advanced oxidation of proteins products (AOPP) and carbonylated proteins (CBO) caused by obesity in cardiac tissue. Besides that, it was observed that ObCap rats presented high levels of malondialdehyde and greater activity of antioxidant enzymes compared to Ob. In conclusion, treatment with capsinoids did not lead to significant positive effects in reducing obesity-induced oxidative stress.

Despite ongoing efforts, the relationship between groin strength and injury remains unclear. The challenge of accurately predicting injuries presents an opportunity for researchers to develop pre-vention strategies to reduce the occurrence of such injuries. Consequently, this issue requires further investigation to obtain insights into effective mitigation strategies. In 120 male soccer players the maximum isometric strength of the hip muscle groups was measured, and the strength ratios were calculated. Previous injury and anthropometric data were registered. Injury data were collected following the FIFA/UEFA consensus. The K- Nearest Neighbour (k-NN), was used to predict the incidence of injury, while the significant predictive variables of the k-NN algorithm were fitted into a multivariate logistic regression model (LR) to analyze the likelihood of players sustaining a groin injury. The LR model determined two variables as significant predictors of groin injury. Players were less likely to sustain a groin injury by 76% for each decrease of the Adductors/Abductors isometric strength ratio in the non-dominant limb (OR = 0.238, CI 95%= [(0.098-0.572]). Players with a history of previous injury had a 67% greater risk of sustaining an injury (OR = 0.333, CI 95%= [(0.1068-1.038]). Isometric hip adductor and abductor strength im-balances of the non-dominant lower limb and a history of previous injury were risk factors for groin injury in soccer players.

Ultrasound imaging is a vital imaging tool in musculoskeletal medicine, with the number of publications on ultrasound-guided surgery increasing in recent years. However, ultrasound imaging has drawbacks, such as operator dependency and image obscurity. Artificial Intelligence (AI) and Deep Learning (DL), a subset of AI, can address these issues. DL methods, including segmentation, detection, and localization of target tissues and medical instruments, potentially allow physicians and surgeons to perform ultrasound-guided procedures more accurately and efficiently. This review summarizes recent advances in ultrasound-guided procedures for musculoskeletal diseases and provides a comprehensive overview of the utilization of AI/DL in ultrasound for musculoskeletal medicine, particularly focusing on ultrasound-guided surgery.

Exoskeleton technology has been shown to be useful for individuals with spinal cord injury (SCI), potentially facilitating their recovery of motor function and social reintegration. However, studies on the safety and usability of exoskeletons are limited. This study aimed to design a powered exoskeleton for SCI and evaluate its safety and usability. Ten healthy adults participated in this study. The prototype exoskeleton featured an adjustable frame, computer-controlled hip and knee joint actuators, and a gait-trigger sensor. The experimental actions included walking, standing, and sitting, with and without the prototype. Safety outcomes included adverse events, vital signs, numerical rating scale (NRS) scores for pain, discomfort, and fatigue, and prototype-human body clearance. Usability outcomes included donning and doffing times, subjective ratings, gait speed, stride length, and kinematic parameters of hip and knee joint angles. Safety outcomes showed no serious adverse events, stable vital signs, minimal NRS scores, and acceptable clearance. Usability outcomes showed high efficiency and received positive ratings. Kinematic parameters showed significant positive correlations between normal walking and walking with the prototype for both hip and knee joint angles, confirming its effectiveness in assisting walking. However, further device improvements and gait parameter tuning are necessary for future clinical application.

Genetics plays an integral role in athletic performance and is increasingly becoming recognised as an important risk factor for injury. Ankle and knee injuries are the most common injuries sustained by soccer players. Often these injuries result in players missing training and matches, which can incur significant costs to clubs. This study aimed to identify genotypes associated with ankle and knee injuries in soccer players and how these impacted the number of matches played. 289 soccer players including 46 professional, 98 semi-professional and 145 amateur players were genetically tested. Ankle and knee injuries and the number of matches played were recorded during the 2014/15 season. Four genes were assessed in relation to injury. Genotypes found to be associated with injury included the TT genotype of the GDF5 gene, TT and CT genotypes of AMPD1 gene, TT genotype of COL5A1 and GG genotype of IGF2 gene. These genes were also associated with a decrease in the number of matches played.

The presence of anti SARS-CoV2-RBD antibody (Anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care Anti-RBD test implemented in person living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 persons with comorbid (PLWH, SLE, CKD) to test anti-RBD assay compared to surrogate viral neutralization (SVNT) as the reference test. We performed linear correlation analysis between anti-RBD vs SVNT and a ROC analyses to ascertain anti-RBD cut-off at 30%, 60%, and 90% inhibition of SVNT to calculate accuracy. Correlations of anti-RBD to SVNT among all groups were excellent with R= 0.7903, R=0.7843, R=0.8153 among non-comorbid, SLE and CKD groups, respectively, with significantly higher correlation among the PLWH group (R=0.8877; p-value=0.0072) compared to non-comorbid group. The accuracy of the anti-RBD test among PLWH and CKD group was similar with the non-comorbid but showed lower sensitivity in the SLE group (p=0.000014). The specificity of the test remained high in all groups. In conclusion, the Anti-RBD test had excellent correlation to SVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect presence of low neutralization capacity, prompting additional vaccination.

.Cellular senescence has emerged as an important driver of aging and age-related disease in the kidney. The activity of β-galactosidase at pH 6 (SA-β-Gal) is a classic maker of senescence in cellular biology. However the predictive role of kidney tissue SA-β-Gal on eGFR loss in chronic kidney disease (CKD) is still not understood. We retrospectively studied the expression of SA-β-Gal in kidney biopsies obtained in a cohort [n=29] of incident patients who were followed up for 3 years as for standard of care. SA-β-Gal staining was approximately 4-fold higher in the tubular compartment of patients with CKD vs. controls [26.0 ± 9 vs. 7.4 ± 6% positive tubuli in patients vs. controls; p < 0.025]. Tubular expressions of SA-β-Gal, but not proteinuria at the time of biopsy correlated with eGFR loss at follow-up; moreover, SA-β-Gal expression in more than 30% of kidney tubules was associated with fast progressive kidney disease. In summary, our study shows that SA-β-Gal is upregulated in the kidney tubular compartment of adult patients affected by CKD, and suggests that tubular SA-β-Gal is associated with accelerated loss of renal function.