Rasheed Gbadegesin

Glomerular diseases (GDs) are a major cause of chronic kidney disease in children. The conventional approach to diagnosis of GDs includes clinical evaluation and, in most cases, kidney biopsy to make a definitive diagnosis. However, in many cases, clinical presentations of different GDs can overlap, leading to uncertainty in diagnosis and management even after renal biopsy. In this report, we identify a family with clinical diagnoses of postinfectious glomerulonephritis and IgA nephropathy in a parent and two children. Renal biopsies were initially inconclusive; however, genetic testing showed that the two individuals diagnosed at different points with IgA nephropathy carried novel segregating pathogenic variants in COL4A5 gene. We were only able to make the final diagnoses in each of the family members after genetic testing and reverse phenotyping. This case highlights the utility of genetic testing and reverse phenotyping in resolving clinical diagnosis in families with unusual co...

Minimal change disease (MCD) is the most common cause of nephrotic syndrome worldwide. For decades, the foundation of the treatment has been corticosteroids. However, relapse rate is high and up to 40% of patients develop frequent relapsing/steroid dependent course and one third become steroid resistant. This requires treatment with repeated courses of corticosteroids, and second and third line immunomodulators increasing the incidence of drug related adverse effects. More recently, there have been reports of a very small subset of Nephrotic Syndrome (NS) patients who are initially steroid sensitive and later become secondarily steroid resistant. The disease course in this small subset is often protracted leading ultimately to end stage kidney disease requiring dialysis or kidney transplantation. Unfortunately, patients with this disease course do not do well post transplantation because 80% of them will develop disease recurrence that will ultimately lead to graft failure. Few appr...

Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents a myriad of questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anti-complement therapy trials either planned or underway, the National Kidney Foundation (NKF) facilitated an all-virtual format scientific workshop entitled, "Improving Clinical Trials for Anti-complement Therapies in Complement-mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anti-complement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, subject risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.

Background: Childhood nephrotic syndrome, if left untreated, leads to progressive kidney disease or death. We quantified the prevalence of steroid-sensitive nephrotic syndrome, steroid-resistant nephrotic syndrome and histological types as the epidemiology of nephrotic syndrome in Africa remains unknown, yet impacts outcomes. Methods: We searched MEDLINE, Embase, African Journals Online and WHO Global Health Library for articles in English or French reporting on childhood nephrotic syndrome in Africa from January 1, 1946 to July 1, 2020. Primary outcomes included steroid response, biopsy defined minimal change disease, and focal segmental glomerulosclerosis (FSGS) by both pooled and individual proportions across regions and overall. Findings: There were 81 papers from 17 countries included. Majority of 8,131 children were steroid-sensitive (64% [95% CI: 63-66%]) and the remaining were steroid-resistant (34% [95% CI: 33-35%]). Of children biopsied, pathological findings were 38% [95% CI: 36-40%] minimal change, 24% [95% CI: 22-25%] FSGS, and 38% [95% CI: 36-40%] secondary causes of nephrotic syndrome. Interpretation: Few African countries reported on the prevalence of childhood nephrotic syndrome. Steroid-sensitive disease is more common than steroid-resistant disease although prevalence of steroid-resistant nephrotic syndrome is higher than reported in European populations. Pathology findings suggest minimal change and secondary causes are common. Scarcity of data in Africa prevents appropriate healthcare resource allocation to diagnose and treat this treatable childhood kidney disease to prevent poor health outcomes. Funding Statement: Funding was provided by the Canadian Institute for Health Research (CIHR) and the National Institute of Health (NIH) for the H3 Africa Kidney Disease Research Network. This research was undertaken, in part, from the Canada Research Chairs program. Declaration of Interests: The authors have no competing interests or conflicts to declare.

1. Jonathan Pelletier, MD* 2. Rasheed Gbadegesin, MD, MBBS† 3. Betty Staples, MD* 1. *Department of Pediatrics and 2. †Department of Pediatric Nephrology, Duke Children's Hospital and Health Center, Durham, NC 1. 1. Reddy P Clinical Approach to Renal Tubular Acidosis in Adult Patients. Reddy P Int J Clin Pract. 2011;65(3):350–360 [OpenUrl][1][CrossRef][2][PubMed][3] 2. 1. Batlle D, 2. Haque SK Genetic Causes and Mechanisms of Distal Renal Tubular Acidosis. Batlle D, Haque SK. Nephrol Dial Transplant. 2012;27(10):3691–3704 [OpenUrl][4][CrossRef][5][PubMed][6][Web of Science][7] 3. 1. Karet FE Mechanisms in Hyperkalemic Renal Tubular Acidosis. Karet FE. J Am Soc Nephrol. 2009;20(2):251–254 [OpenUrl][8][Abstract/FREE Full Text][9] 4. 1. Haque SK, 2. Ariceta G, 3. Batlle D Proximal Renal Tubular Acidosis: A Not So Rare Disorder of Multiple Etiologies. Haque SK, Ariceta G, Batlle D Nephrol Dial Transplant. 2012;27(12):4273–4287 [OpenUrl][10][CrossRef][11][PubMed][12][Web of Science][13] 5. 1. Gbadegesin R, 2. Foreman W 1. Chand DH, 2. Valentini RP Renal Tubular Acidosis. Gbadegesin R, Foreman W In: Chand DH, Valentini RP, eds. Clinician's Manual of Pediatric Nephrology. 1st ed. Singapore: World Scientific Publishing Co; 2011 The body temporarily buffers hydrogen ions (H+) with plasma proteins, hemoglobin, and bicarbonate (HCO3−), but H+ must be excreted to prevent acidosis. The major functions of the kidneys in acid-base homeostasis are to excrete H+ and reabsorb HCO3−. Failure to perform these functions results in HCO3− wasting, leading to renal tubular acidosis (RTA), which is categorized into 3 major groups: distal (type I), proximal (type II), and hyperkalemic (type IV) RTA. Excretion of H+ to balance acid production is primarily the function of the distal convoluted tubule and collecting duct (DCT/CD), where α-intercalated cells actively transport H+ into the tubule. Secreted H+ combines with ammonia to form ammonium in the DCT/CD lumen. Because of its positive charge, ammonium cannot diffuse out of the tubular lumen, and it is passed in the urine. In distal RTA, α-intercalated cells cannot secrete sufficient H+ into the tubular lumen, resulting in decreased … [1]: {openurl}?query=rft.jtitle%253DInternational%2Bjournal%2Bof%2Bclinical%2Bpractice%26rft.stitle%253DInt%2BJ%2BClin%2BPract%26rft.aulast%253DReddy%26rft.auinit1%253DP.%26rft.volume%253D65%26rft.issue%253D3%26rft.spage%253D350%26rft.epage%253D360%26rft.atitle%253DClinical%2Bapproach%2Bto%2Brenal%2Btubular%2Bacidosis%2Bin%2Badult%2Bpatients.%26rft_id%253Dinfo%253Adoi%252F10.1111%252Fj.1742-1241.2009.02311.x%26rft_id%253Dinfo%253Apmid%252F21314872%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1111/j.1742-1241.2009.02311.x&link_type=DOI [3]: /lookup/external-ref?access_num=21314872&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [4]: {openurl}?query=rft.jtitle%253DNephrol%2BDial%2BTransplant%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fndt%252Fgfs442%26rft_id%253Dinfo%253Apmid%252F23114896%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/external-ref?access_num=10.1093/ndt/gfs442&link_type=DOI [6]: /lookup/external-ref?access_num=23114896&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [7]: /lookup/external-ref?access_num=000310631500007&link_type=ISI [8]: {openurl}?query=rft.jtitle%253DJ%2BAm%2BSoc%2BNephrol%26rft_id%253Dinfo%253Adoi%252F10.1681%252FASN.2008020166%26rft_id%253Dinfo%253Apmid%252F19193780%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink?linkType=ABST&journalCode=jnephrol&resid=20/2/251&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [10]: {openurl}?query=rft.jtitle%253DNephrol%2BDial%2BTransplant%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fndt%252Fgfs493%26rft_id%253Dinfo%253Apmid%252F23235953%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [11]: /lookup/external-ref?access_num=10.1093/ndt/gfs493&link_type=DOI [12]: /lookup/external-ref?access_num=23235953&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [13]: /lookup/external-ref?access_num=000312645800008&link_type=ISI

OBJECTIVES/GOALS: To ameliorate the leaky pipeline of physician-scientists, we must address the factors that cause medical trainees to disengage from research. Here we describe the development of standardized Physician-Scientist Training Program guidelines that may be implemented across disciplines to address these challenges. METHODS/STUDY POPULATION: Maintenance of a robust pool of physician-scientists is critical to meet the rapidly growing need for novel therapeutics. A variety of factors contribute to the decline of this pool. Key among these are a lengthy training period that segregates research from clinical training, thus impeding research progress and milestones that allow for a successful research career. Through engagement of residency program directors and Vice Chairs of Research, we have created a series of guidelines that promote residency research tracks and enable better integration of research and clinical training time. Guidelines have been piloted in the Departmen...

Introduction: Although it is known that children with nephrotic syndrome (NS) are at greater risk for certain complications, the frequency of these complications and predisposing risk factors are poorly defined. In particular, nephrotic syndrome has long been considered a hypercoagulable state. Risk for development of venous thromboembolism (VTE) is known to be increased in the setting of an active infection. The objective of this study was to determine the prevalence of infection and VTE among a cohort of hospitalized children with NS, and the association of these complications on outcomes. Methods: Records of hospitalized children with NS admitted to any of 17 participating pediatric hospitals across North America from 2010-2012 were included. Data including demographics, clinical pattern of NS, renal biopsy results, number of hospitalizations, nephrotoxic medication usage, infection and VTE history were recorded. Descriptive statistics were used to determine prevalence of infecti...

Nephrotic syndrome (NS) results in hypercoagulability and increased risk of infection. Furthermore, infection increases the risk of venous thromboembolism (VTE). Our objective was to determine the prevalence of infection, VTE, and the associated outcomes among a cohort of hospitalized children with NS. All children with NS admitted to 17 pediatric hospitals across North America from 2010 to 2012 were included. Prevalence of infection and VTE was determined. Wilcoxon rank-sum and logistic regression were performed. Seven-hundred thirty hospitalizations occurred among 370 children with NS. One-hundred forty-eight children (40%) had ≥ 1 infection (211 episodes) and 11 (3%) had VTE. Those with VTE had infection more frequently (p = 0.046) and were younger at NS diagnosis (3.0 vs. 4.0 years; p = 0.008). The most common infectious pathogen identified was Streptococcus pneumoniae. The median hospital length of stay for those with infection [10 vs 5 days (p < 0.0001)] or VTE [22 vs 6 day...

1. Jonathan Pelletier, MD* 2. Rasheed Gbadegesin, MD, MBBS† 3. Betty Staples, MD* 1. *Department of Pediatrics and 2. †Department of Pediatric Nephrology, Duke Children's Hospital and Health Center, Durham, NC 1. 1. Reddy P Clinical Approach to Renal Tubular Acidosis in Adult Patients. Reddy P Int J Clin Pract. 2011;65(3):350–360 [OpenUrl][1][CrossRef][2][PubMed][3] 2. 1. Batlle D, 2. Haque SK Genetic Causes and Mechanisms of Distal Renal Tubular Acidosis. Batlle D, Haque SK. Nephrol Dial Transplant. 2012;27(10):3691–3704 [OpenUrl][4][CrossRef][5][PubMed][6][Web of Science][7] 3. 1. Karet FE Mechanisms in Hyperkalemic Renal Tubular Acidosis. Karet FE. J Am Soc Nephrol. 2009;20(2):251–254 [OpenUrl][8][Abstract/FREE Full Text][9] 4. 1. Haque SK, 2. Ariceta G, 3. Batlle D Proximal Renal Tubular Acidosis: A Not So Rare Disorder of Multiple Etiologies. Haque SK, Ariceta G, Batlle D Nephrol Dial Transplant. 2012;27(12):4273–4287 [OpenUrl][10][CrossRef][11][PubMed][12][Web of Science][13] 5. 1. Gbadegesin R, 2. Foreman W 1. Chand DH, 2. Valentini RP Renal Tubular Acidosis. Gbadegesin R, Foreman W In: Chand DH, Valentini RP, eds. Clinician's Manual of Pediatric Nephrology. 1st ed. Singapore: World Scientific Publishing Co; 2011 The body temporarily buffers hydrogen ions (H+) with plasma proteins, hemoglobin, and bicarbonate (HCO3−), but H+ must be excreted to prevent acidosis. The major functions of the kidneys in acid-base homeostasis are to excrete H+ and reabsorb HCO3−. Failure to perform these functions results in HCO3− wasting, leading to renal tubular acidosis (RTA), which is categorized into 3 major groups: distal (type I), proximal (type II), and hyperkalemic (type IV) RTA. Excretion of H+ to balance acid production is primarily the function of the distal convoluted tubule and collecting duct (DCT/CD), where α-intercalated cells actively transport H+ into the tubule. Secreted H+ combines with ammonia to form ammonium in the DCT/CD lumen. Because of its positive charge, ammonium cannot diffuse out of the tubular lumen, and it is passed in the urine. In distal RTA, α-intercalated cells cannot secrete sufficient H+ into the tubular lumen, resulting in decreased … [1]: {openurl}?query=rft.jtitle%253DInternational%2Bjournal%2Bof%2Bclinical%2Bpractice%26rft.stitle%253DInt%2BJ%2BClin%2BPract%26rft.aulast%253DReddy%26rft.auinit1%253DP.%26rft.volume%253D65%26rft.issue%253D3%26rft.spage%253D350%26rft.epage%253D360%26rft.atitle%253DClinical%2Bapproach%2Bto%2Brenal%2Btubular%2Bacidosis%2Bin%2Badult%2Bpatients.%26rft_id%253Dinfo%253Adoi%252F10.1111%252Fj.1742-1241.2009.02311.x%26rft_id%253Dinfo%253Apmid%252F21314872%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1111/j.1742-1241.2009.02311.x&link_type=DOI [3]: /lookup/external-ref?access_num=21314872&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [4]: {openurl}?query=rft.jtitle%253DNephrol%2BDial%2BTransplant%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fndt%252Fgfs442%26rft_id%253Dinfo%253Apmid%252F23114896%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: /lookup/external-ref?access_num=10.1093/ndt/gfs442&link_type=DOI [6]: /lookup/external-ref?access_num=23114896&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [7]: /lookup/external-ref?access_num=000310631500007&link_type=ISI [8]: {openurl}?query=rft.jtitle%253DJ%2BAm%2BSoc%2BNephrol%26rft_id%253Dinfo%253Adoi%252F10.1681%252FASN.2008020166%26rft_id%253Dinfo%253Apmid%252F19193780%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [9]: /lookup/ijlink?linkType=ABST&journalCode=jnephrol&resid=20/2/251&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [10]: {openurl}?query=rft.jtitle%253DNephrol%2BDial%2BTransplant%26rft_id%253Dinfo%253Adoi%252F10.1093%252Fndt%252Fgfs493%26rft_id%253Dinfo%253Apmid%252F23235953%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [11]: /lookup/external-ref?access_num=10.1093/ndt/gfs493&link_type=DOI [12]: /lookup/external-ref?access_num=23235953&link_type=MED&atom=%2Fpedsinreview%2F38%2F11%2F537.atom [13]: /lookup/external-ref?access_num=000312645800008&link_type=ISI

It is widely believed that malaria causes diarrhea. Yet, national and international diarrheal diseases control programs are silent about the overlap between these two major public health problems that coexist in most tropical countries. To test the hypothesis that malaria is associated with diarrhea and to define the role of malaria in morbidity due to diarrhea, 522 children 6-60 months of age presenting with acute diarrhea to the Children's Emergency Ward of the University College Hospital in Ibadan, Nigeria were routinely screened by means of thin and thick blood films for malaria parasitemia. Controls, without diarrhea, were studied in parallel. Detailed clinical features were recorded for every patient. Sixty-eight (13%) of the 522 diarrhea patients screened had malaria parasitemia. Among the controls (who had similar distributions of admission temperature, hemoglobin types, glucose-6-phosphate dehydrogenase deficiency, and prior treatment with antimalarial drugs), parasitemia was not significantly different, occurring in 56 (17.9%) of 313. In the dry season, however, a significantly higher prevalence of parasitemia was observed among the control group (15.5%) than in the diarrhea group (7.0%) (P = 0.004). Parasitemia was significantly more common in the dehydrated diarrhea patients than their well-hydrated counterparts (25% of 56 versus 11% of 466; P < 0.005). There were no significant differences in admission temperature, the presence of vomiting, or the home use of oral rehydration fluids between the dehydrated and the well-hydrated subsets of diarrhea patients. Consideration of parasite densities did not alter any of the foregoing relationships. These data contradict the widely held view that diarrhea is a symptom of malaria or that malaria causes diarrhea. They do, however, provide support for examining blood smears at least in dehydrated children with diarrhea in malaria-endemic areas and giving immediate antimalarial therapy to those who have malaria parasitemia.

NE (typhlitis) is a potentially life-threatening disease process characterized by bowel wall edema, ulceration, and hemorrhage in an immunosuppressed patient. We report a 15-year-old boy status post deceased donor renal transplantation who presented with fever, abdominal pain, and diarrhea. Laboratory studies revealed neutropenia 5 days prior to admission, and abdominal computed tomography revealed bowel wall thickening in the cecum consistent with NE. He was treated with piperacillin-tazobactam and gentamicin and recovered. To our knowledge, this is the first report of a case of NE in a pediatric kidney transplant recipient.

Nephrotic syndrome is among the most common forms of kidney disease seen in children. Steroid resistant nephrotic syndrome (SRNS) is only responsible for ~20 % of all cases of NS in children; however the SRNS variant is the most common glomerular cause of end stage kidney disease (ESKD) in children. SRNS is characterized by different pathologic changes on kidney biopsy, in children the most common histologic variants are FSGS and minimal change disease. The pathogenesis of FSGS has not been completely delineated; however there is growing evidence to suggest that it is a primary defect of the podocyte. Candidate circulating factors such as cardiotrophin like cytokine-1 (CLC-1) and the soluble form of urokinase-type plasminogen activator receptor (sUPAR) have also been implicated in disease pathogenesis. The treatment of SRNS is challenging, as only about 30 % of all cases will respond to currently available therapies, yet response to therapy is the most important determinant of future progression to ESKD. The risk of recurrence of FSGS in kidney transplant is estimated at 30 %, with a lower risk (8 %) in patients with genetic FSGS. Further studies of familial and non- familial forms of SRNS are needed in order to elucidate disease mechanisms and identify potential future therapeutic targets.

A study of bacterial organisms isolated from 65 Nigerian children who had urinary tract infection (UTI) is reported. The predominant isolate in both inpatients and outpatients was Klebsiella species which accounted for 52.8% of cases. Escherichia coli, Pseudomonas spp and Proteus spp accounted for 25.0%, 15.3% and 5.5% of isolates, respectively. All isolates were poorly sensitive to the common first-line drugs used in UTI in our environment, namely, cotrimoxazole and ampicillin, but exhibited good sensitivity to nalidixic acid, nitrofurantoin and ofloxacin. It is recommended that nitrofurantoin and nalidixic acid be used for blind treatment of UTI in Nigerian children in Ibadan while results of culture and sensitivity are awaited. Continuous monitoring of the pattern of organisms isolated in childhood UTI and their antibiotic resistance patterns is recommended as an essential step in guiding blind antibiotic therapy in such cases.

To identify possible risk factors for persistent diarrhoea, 307 children with acute diarrhoea presenting at the University College Hospital, Ibadan, Nigeria over a 10-month period from July 1993 to April 1994 were followed up prospectively until the resolution of the illness. The children were aged 6-60 months. In 36 (11.7%) of them, diarrhoea became persistent (i.e. lasted more than 14 days). This hospital frequency of 11.7% of persistent diarrhoea is, as expected, higher than the figures from previous community-based studies of diarrhoea from Nigeria. The major factor associated with persistent diarrhoea was poor nutritional status. Mean z scores of weight-for-height and weight-for-age were significantly lower in the persistent diarrhoea group, while mean z scores of height-for-age were similar in the two groups. The frequencies of occurrence of undernutrition, marasmus and kwashiorkor were also higher in the persistent diarrhoea group. Therefore, in common with studies from other...

Major congenital malformations are unrecognised as a major cause of neonatal morbidity in many African countries. We have studied the contribution of major congenital malformations to morbidity among neonates referred to the University College Hospital, Ibadan, Nigeria over a four year period (1992-1995). Major congenital malformations were found in 11.1% of 1276 neonatal referrals and ranked fourth among the most common problems in such neonates (after sepsis, jaundice and tetanus but ahead of prematurity and perinatal asphyxia). The commonest malformations seen included spina bifida (22.5%), anorectal malformation (13.4%), omphalocoele (9.9%) and tracheo-oesophageal fistula (8.5%). Neonates with major congenital malformations presented significantly earlier than other neonates but mortality during the first admission was similar in the two groups. It is concluded that major congenital malformations pose a significant burden of morbidity in referred neonates to the hospital. Health...

Although both malaria and diarrhoea are major public health problems in developing countries, and separately each has been the subject of intense research, few studies have investigated the interaction between these two conditions. The interaction between diarrhoea and malaria among children aged 4 months to 12 years in two tertiary health-care facilities, University College Hospital, Ibadan, and Lagos University Teaching Hospital, Lagos, Nigeria was studied. In Ibadan, the prevalence of diarrhoea among the cerebral malaria patients on admission as 11.7% (7/60) compared to 9.3% (215/2312) among other admissions in 1990 (chi square = 0.16; p = 0.6913). Similarly, no significant difference in the prevalence of diarrhoea was found between the cerebral malaria patients (14.3%) and other patients (16.1%) seen in Lagos in 1992 (chi square = 0.06, p = 0.81). Thus, cerebral malaria does not seem to be associated with an increased or decreased prevalence of diarrhoea when compared with other...

A group of 42 children with renal diseases seen at the University College Hospital Ibadan were studied in order to evaluate the usefulness of the height/plasma creatinine formula of Schwartz et al i.e. GFR ml/min/1.73 m2 = 0.55 x Height (cm)/Plasma creatinine (mg/dl) in identifying children with renal impairment. The children were divided into 2 groups of those with GFR as measured by endogenous creatinine clearance (Ccr) < 60 ml/min/1.73 cm2 and those with CCr > 60 ml/min/1.73 cm2. There were 21 children in each group. In detecting patients with Ccr less than 60 ml/min/1.73 m2, Schwartz formula had a sensitivity of 52%, a specificity of 100%, a positive predictive value of 100% and a negative predictive value of 68%. It is concluded that in detecting patients with impaired renal function who may need more accurate methods of estimating GFR, Schwartz formula has a low sensitivity and therefore may not be useful as a screening method.

The report concerns an outbreak of neonatal Klebsiella septicaemia at the University College Hospital, Ibadan, Nigeria, between October and November 1991. Mortality, 35.7%, was higher in the preterm babies than in the term babies (p < 0.05). The important predisposing factors to infection identified were birth asphyxia, necessitating active resuscitation, prematurity, prolonged rupture of the membranes and maternal intrapartum pyrexia. The Klebsiella species isolated from the babies and the hospital environment during the outbreak were of the multiple drug resistant type. Preventive measures and the need for a continual bacteriological surveillance are highlighted.

The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort. This was a prospective study in which 127 children (age range 8-17 years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2 g/g) were eligible. Comparisons were made between children with prevalent (N = 67) and incident (N = 60) disease at the study enrollment visit. The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p = 0.01) and pain interfer...

Increased vascular stiffness is an established risk marker of cardiovascular diseases (CVD) in adults with end-stage renal disease, but its role in pediatric patients remains to be defined. We prospectively examined arterial compliances of adolescents and young adults on hemodialysis (HD) using diastolic pulse wave analysis (DPWA). Each of the ten HD patients (age 17.3 +/- 3.9 years; mean +/- SD) had two DPWA tests within a three-week time period. DPWA measurement was performed before and hourly until the end of three-hour HD. Pre-HD large artery elasticity index (LAEI) was reduced in one patient and small artery elasticity index (SAEI) was reduced in another. Neither patient was hypertensive. Eight other patients had a reduction in both LAEI and SAEI. Among them, six patients had systolic and/or diastolic hypertension, and the other two were normotensive. Serum phosphorus correlated positively with stroke volume and cardiac output indices and negatively with SAEI. The reduction in BP during HD correlated with the amount of fluid removal. LAEI and SAEI were unchanged during HD. In conclusion, the reduction in LAEI and/or SAEI was observed in four normotensive patients, suggesting hypertension was not the only contributing factor for the reduced arterial compliances in our patients. The association between SAEI and serum phosphorus suggests that SAEI derived from DPWA can potentially be an early non-invasive, operator-independent, and volume-independent marker of CVD in adolescents and young adults receiving HD. Longitudinal studies with a larger sample size are needed to confirm our observation and speculation.

OBJECTIVES. Mutations in each of the NPHS1, NPHS2, WT1, and LAMB2 genes have been implicated in nephrotic syndrome, manifesting in the first year of life. The relative frequency of causative mutations in these genes in children with nephrotic syndrome manifesting in the first year of life is unknown. Therefore, we analyzed all 4 of the genes jointly in a large European cohort of 89 children from 80 families with nephrotic syndrome manifesting in the first year of life and characterized genotype/phenotype correlations. METHODS. We performed direct exon sequencing of NPHS1, NPHS2, and the relevant exons 8 and 9 of WT1, whereas the LAMB2 gene was screened by enzymatic mismatches cleavage. RESULTS. We detected disease-causing mutations in 66.3% (53 of 80) families (NPHS1, NPHS2, WT1, and LAMB2: 22.5%, 37.5%, 3.8%, and 2.5%, respectively). As many as 84.8% of families with congenital onset (0–3 months) and 44.1% with infantile onset (4–12 months) of nephrotic syndrome were explained by m...

We report simple and reproducible PCR-RFLP typing methods for the polymorphisms in the ICAM-1, E-selectin and PECAM-1 genes. The genotype and allele frequencies detected in a normal UK population did not deviate significantly from the Hardy-Weinberg equilibrium; neither did they differ from frequencies previously reported using SSP or SSCP methods.