Includes abstract. / Includes bibliographical references (leaves 64-72). / Posterior urethral valve (PUV) is a congenital obstructing membrane of the male urethra. It is the commonest cause of bladder outlet obstruction in male children. PUV as a cause of obstructive uropathy is an important cause of end stage renal failure (ESRF) in children. Early detection and surgical intervention can slow down progression to ESRF.

Introduction: Dialysis is a temporary renal replacement therapy (RRT) to keep the child healthy and alive when in end stage kidney failure (ESKF) while being worked up for kidney transplant, the preferred treatment. Chronic peritoneal dialysis (PD) is the preferred first choice of dialysis modality in many centers because of its advantages over hemodialysis (HD). In recent years, there have been advances to improve the performance and survival of PD as a modality for renal replacement. Despite these improvements, complications still arise, sometimes warranting a switch to HD. We sought to investigate the extent to which children at Red Cross War Memorial Children's Hospital (RCWMCH) drop-out from chronic PD and describe some of the reasons for this drop-out. Objectives: To describe the rate of drop-out of children with ESKD from chronic PD, the timing and factors associated with this drop-out at RCWMCH. Methods: This was a retrospective descriptive study, carried out in the renal ward, E2, of RCWMCH in Cape Town. Eligible participants were identified from the renal transplant waiting lists over the study period. Patient folders were retrieved following ethical approval, for extraction of relevant data. Outcome measures: Proportion dropping-out during the study period (permanent switch to HD or death from PD related complications), factors associated with dropout and time from initiation of chronic PD to drop-out. Utility of the study: Findings from this study will help in designing strategies to improve chronic PD patient outcomes, prolongation of PD technique survival and reducing the costs of chronic dialysis at RCWMCH. Results: A total of 111 children were listed for transplantation between January 2009 and December 2018, 67 were treated with PD. Complete data was available for 52 of the 67 children who received PD. Overall, 17/52 (32.7%) dropped-out during the study period. Most (>50%) of them dropped-out within the first 1-2 years of being on PD. The only significant associated factor was one or more episodes of peritonitis. Recommendation: There is a need to step up measures to prevent peritonitis in chronic PD patients so as to prolong stay on PD until a kidney transplant is available, as well as improve kidney transplantation rates. Dissemination of results: Results were presented at the Department of Pediatrics and Child Health Research Day 2019 and at the world congress of nephrology international conference 2021. Results will be submitted for publication in a peer reviewed journal.

Background: Tuberculosis remains a major challenge in transplantation particularly in endemic countries. The incidence, clinical manifestations, and optimal investigations for TB specifically in the paediatric post-transplant population have not yet been adequately studied. This study aims to describe the incidence, clinical presentation and outcomes of tuberculosis in paediatric kidney transplant recipients and to assess the impact of Isoniazid prophylaxis. Methods: Single-centre retrospective descriptive analysis of children who received kidney transplants from 1995-2019. The cohort was stratified according to receipt of isoniazid prophylaxis which began in 2005. Results: 212 children received a kidney transplant during the study period. Median age at transplantation was 11.2 years (IQR: 2.2 - 17.9) and 56% were males. Tuberculosis was diagnosed in 20 (9%) children, with almost two thirds (n=12) occurring within the first year post-transplant. The main presenting symptoms included fever (n=13/20), weight loss (n=12/20) and cough (n=10/20). Tuberculin skin test was positive in four of 20 children. Coinfection with Ebstein Barr virus, Cytomegalovirus or Staphylococcus was found in five children. Due to interactions an up to three fold increase in calcineurin inhibitor dose was required to maintain therapeutic blood levels. Isoniazid prophylaxis was protective against development of tuberculosis (p=0.04). ) and was associated with fewer infections within the first year of transplantation although this was not statistically significant (p = 0.3). Gender, age and type of allograft were not significant risk factors for developing tuberculosis. All the tuberculosis infections were successfully treated. There was graft and patient survival of 100%. Conclusion: Kidney transplant recipients have a high risk of tuberculosis. Diagnosis remains a challenge. Frequent and meticulous monitoring of immunosuppression drug levels during treatment of TB is required to avoid loss of patient or graft. Isoniazid prophylaxis protects against development of TB in this population. (HREC 463/2020)

Background: Crescentic glomerulonephritis represents the extreme end on the spectrum of glomerular injury. It can result from a wide range of disease conditions and clinically is marked by a rapid deterioration in renal function over days, weeks or months. Although rare, crescentic glomerulonephritis is an important entity to recognize because prompt treatment can improve patient outcomes significantly. Literature on the prevalence, clinical presentation, aetiology and outcome of histologically proven crescentic glomerulonephritis among children, in Africa, is scanty. Most of what is known about this entity is extrapolated from adult studies and from paediatric studies that have for the most part been conducted outside the African continent. Objective: This study was conducted in order to determine the incidence, clinical presentation, aetiology and outcome of histologically proven crescentic glomerulonephritis in children presenting to the Red Cross Children's Hospital, Cape Town, South Africa. Methods: This was a retrospective folder review in which the renal biopsy records of children less than 18 years old who had had native kidney biopsies performed between 2004 and July 2015 at the Red Cross Children's Hospital were reviewed. The clinical notes of patients found to have been diagnosed with crescentic glomerulonephritis were traced so as to extract demographic and clinical information which was then recorded onto the study data sheet. No attempt to contact patients or their families was made. Data analysis with regard to the incidence, the clinical features and the outcome of crescentic glomerulonephritis was done using SPSS version 22. Results: A total of 470 native kidney biopsies were performed in the period under review. Of these, 24 had crescentic glomerulonephritis, accounting for an incidence of 5.1 %. The sub-types of crescentic glomerulonephritis were immune-complex in 19 (80%), Pauci-immune in 2 (8 %), unspecified type in 3 (12 %) and no child had the anti-glomerular basement membrane subtype. The underlying aetiology of the immune complex sub-type was post-infectious in 11(57.9%), idiopathic in 4(21%), HSP/IgA nephropathy in 2 (10.5%), SLE in 1 (5.3%) and mesangiocapillary glomerulonephritis in 1(5.3%). Fourteen of the subjects were male thus giving a male to female ratio of 1.4 while the mean age of the children was 8.3 [range- 1 to 14 years]. The commonest clinical features were hypertension (90%), nephrotic range proteinuria (80%), macroscopic haematuria (57%), oedema (94%) and anaemia (88%). None of these had a statistically significant association to the renal outcome. Ten (77%) out of the 13 children with crescentic glomerulonephritis who were followed up for more than a year were found to have either died, had residual renal dysfunction or been transplanted at the last clinical contact. Conclusion: Crescentic glomerulonephritis was diagnosed in 5.1% of paediatric native renal biopsies which is consistent with what has been reported elsewhere. Unlike reports from other geographical areas the vast majority (80%) of the cases had immune-complex glomerulonephritis with a suspected post-infectious aetiology in over half of these. Similar to earlier reports from South Africa the outcome was poor in most (77%) of the patients. Further research is required to characterise the factors that make post-infectious glomerulonephritis particularly severe in this population.

Background: Despite the undeniable diagnostic benefits of urodynamic studies (UDS), their adoption into clinical practice in Africa has been slow. This study aimed to review the use of invasive UDS in children at a tertiary paediatric hospital in South Africa. Methods: A retrospective analysis of 1108 UDS was conducted. Patient demographic characteristics, primary diagnosis, indication and urodynamic outcomes were reviewed. Presence of urodynamic high-risk features were documented, and a comparison was made between the first study and follow-up study. Results: This study revealed increasing trends in the use of UDS from 2015. Referrals were from Urology (37.7%), Spinal defects clinic (34.4%), Nephrology (20.8%) and other departments (7.0%). The most common reason for referral was review of medical treatment (36.5%). Spinal dysraphism (58.3%) accounted for the majority of conditions seen. Majority (59.1%) of the patients were receiving more than one type of bladder treatment at the time of their first study, with clean intermittent catheterisation (46.5%) being the most common form of bladder management. 97.5% of studies were performed using transurethral bladder catheterization. Urodynamic diagnosis was neurogenic in 74.0%, anatomical (12.2%), functional (8.8%) and normal (5.0%). There was statistically significant improvement in bladder compliance, detrusor leak point pressure and detrusor sphincter dyssynergia between the first study and a subsequent study following therapeutic intervention. Conclusion: The unique ability of UDS to demonstrate changes in detrusor pressures, which is a common reason for therapy failure, makes UDS an invaluable tool in the diagnosis and management of children with lower urinary tract dysfunction.

The most useful drugs in the management of nephrotic syndrome are the corticosteroids. These drugs are as well known for their adverse effects as they are for their therapeutic advantages. The two most common paediatric side effects are suppression of linear growth and posterior subcapsular cataracts. Both of these untoward effects are insiduous and therefore less easily perceived. Although many workers have studied the growth inhibiting effects of the corticosteroids in the various diseases e.g. asthma, very little work was done to investigate these effects in patients with nephrotic syndrome. Furthermore, the Renal Clinic, King Edward VIII Hospital, Durban continues to use a daily regime of prednisone instead of the alternate day regime which is widely recommended to minimise growth retardation. This study was therefore undertaken to investigate the growth inhibiting effects of repeated courses of daily, high-dose prednisone in African and Indian children with nephrotic syndrome. All children with nephrotic syndrome with relevant data in their records and with no other chronic illness were selected from the Renal Clinic. Of the 125 selected, 87 children had been treated with prednisone for an average of 35,9 weeks and 38 had been treated symptomatically. The heights of those that received prednisone were measured at an averace of 77 weeks after completion of therapy. The mean height standard deviation score (SDS) of the treatment and control groups of Indian children were -1,06 and -0,92 respectively, both being between the 10th and 25th percentile, whilst the mean height SDS of the treatment and control groups of African children were -1,82 (just below the 5th percentile) and -1,77 (between the 5th and 10th percentile) respectively. From the results, it is evident that repeated courses of daily prednisone therapy, even when it exceeds 36 weeks, does not inhibit growth in both African and Indian children. Although there was no significant difference between the races and sexes with respect to growth and corticosteroid therapy, this study does confirm earlier reports that most of the African children with nephrotic syndrome had obvious glomerular lesions whilst most of the Indians had minimal change nephrotic syndrome. / Thesis (M.Med.)-University of Natal, Durban, 1986.