Includes bibliographical references. / End Stage Kidney Disease (ESKD) is a global public health problem with an enormous economic burden. In resource limited settings like South Africa management of End Stage Kidney Diseases is rationed to the most transplantable candidates. Racial and socio-economic inequalities in selecting candidates have been documented in a South Africa despite the availability of guidelines. No data is available on selection outcomes using the current 2010 prioritization guidelines of Western Cape. We audited the outcome of patients assessed for the renal replacement therapy at Groote Schuur hospital. A retrospective analytic study of patients presented to the renal replacement therapy committee was conducted in the renal unit of Groote Schuur Hospital. Outcome letters, proceedings from the committee meetings and the hospital database were sources of data used. All new patients presented between 2008 and 2012 were included in the study. Data entry and statistical analysis was done using SPSS v.22. A total of 734 ESKD patients were assessed for renal replacement therapy between January, 2008 and December, 2012. During that period, there were 564 new patients, of which more than half (53.9%) were not selected for the program. Following the introduction of the new prioritization criteria a trend towards increasing number of patients presented and accepted was noted. More males were presented (M: F = 1.3) and most patients were below the age of 50yrs (n=478, 84.8%). Half of the patients came from low socioeconomic areas. There were no significant differences in socio-demographic factors before and after introduction of the new guidelines. Clinically they had advanced disease with either uremic (n=181, 44.4%) or fluid overload (n=179, 43.9%) symptoms as their major presentation. The underlying causes were Hypertension (40.6%), Diabetes (14.4%) and chronic Glomerulonephritis (15.8%). Predictors of rejection from the program included age above 50 years, unemployment and a poor psychosocial assessment. Substance abuse and Diabetes also showed a statistical significant association with the likelihood of being rejected. Race and marital status were not predictors. Efforts to allocate more resources should continue in view of the loss of young and potential productive life. Advanced presentation of patients with ESRD represents challenges in early diagnosis and referral in the current system. Community screening programs and improved access to knowledgeable clinicians at the primary level is advocated. The use of new selection guidelines have not led to an increase in selection inequalities.

Introduction: Kidney biopsy supports diagnoses, choice of treatment and prognostication in management of kidney diseases. Complications associated with this procedure varies among countries depending on several clinical and technical factors. This Systematic review and meta-analysis aims to report on these complications in low and middle-income countries (LMIC) and compare the burden of complications across different regions. Methods: Two independent reviewers searched studies from 1st January 1980 to 31st December 2017 in PubMed, Cochrane Reviews and African Journals Online. The study-specific estimates were pooled through a random-effects model meta-analysis to obtain an overall summary estimate of major complications across studies. Statistical heterogeneity was evaluated by the Cochrane's Q statistic. Results: 35 studies reporting on 18,456 kidney biopsies met the inclusion criteria. The overall rate of kidney biopsy complications was 14.0% (95% CI 10.0-18.0%).Major complications occurred in 1.3% (95% CI 0.8 – 2.4%) whilst minor complications were 10.9% (95% CI 0.07.4-14.9%). LMIC in Europe and Central Asia had the highest complications 21.4% (95% CI 19.1 – 23.8%) while East Asia and the Pacific had the least rates 7.9% (95% CI 1.8 – 17.7%); p< 0.001. Blind procedures had the highest overall complications, 21.2% (95% CI 17.6 – 25.0%), followed by pre-marking using ultrasound [13.9% (95% CI 7.8-21.3%) and least complications with real-time ultrasound (p=0.003). Death occurring post kidney biopsy was reported in 2 patients. Conclusion: Major complications associated with kidney biopsies in LMIC were low. However, minor complications still occur in significant proportions. Ultrasound-guided kidney biopsies and appropriate training will mitigate some of these risks.

Background and purpose: With the advent of antiretroviral therapy, HIV-infected individuals now live longer and are at increased risk of chronic kidney disease (CKD). Also, recent studies indicate a genetic predisposition to CKD in the African HIV population. This work investigated the prevalence of CKD (and its correlates) in the global and local HIV population and proceeded to investigate the diagnostic utility of urinary transforming growth factor-beta-1 (TGF-β1) for CKD in the HIV population and determine the association between polymorphisms of TGF-β1 gene and prevalent CKD. Methods: A meta-analysis was performed to document the prevalence of CKD in the global HIV population. From the local HIV population in Nigeria, the prevalence of CKD and traditional risk factors for cardiovascular disease was determined. Using ELISA, TGF-β1 levels was assayed in the urine samples of HIV patients with or without CKD to investigate the ability of urinary TGF-β1 to diagnose early CKD. SNP genotyping of rs1800469, rs1800470, rs1800471, rs121918282 in TGF-β1, rs60910145 (APOL1), rs73885319 (APOL1), rs71785313 (APOL1) and rs743811 (HMOX1) was performed using predesigned TaqMan genotyping assays. Results: Using meta-analytic methods, the global pooled CKD prevalence was 6.4% (95%CI 5.2–7.7%) with MDRD, and 4.8% (2.9–7.1%) with CKD-EPI. Among the WHO regions, Africa had the highest MDRD-based prevalence, 7.9% (5.2-11.1%) with the West African subregion carrying the heaviest burden, 14.6% (9.9- 20.0%). Among the local HIV population, using the CKD-EPI equation, the prevalence of CKD was 13.4% (11.6- 15.4%). Hypertension prevalence was 26.7% (25.5-28.0%); diabetes 5.6% (4.5-6.7%); obesity 8.3% (7.6-9.1%) and dyslipidaemia 29.1% (26.1-32.1%). HIV-infected individuals with CKD had significantly higher levels of urinary TGF-β1-creatinine ratio (uTGFβ1Cr) after controlling for potential confounding factors in regression models. However, within the CKD-HIV group, uTGFβ1Cr reduced as CKD stage worsened. The presence of APOL1 genetic risk independently increased the risk of CKD (OR 2.54, 95% CI 1.44-4.51) in the HIV population while the TGF-β1 SNP, rs1800470, appeared to have a protective effect (OR 0.44 (95% CI 0.20-0.97). There was no significant association between HMOX1 SNPs and CKD occurrence. Conclusion: There is a high prevalence of CKD (and other cardiovascular risk factors) in the adult HIVpopulation. Urinary TGF-β1 may be useful in the non-invasive detection of early CKD in the HIV population. Genetic testing may be used to predict the risk of CKD in the HIV population.

Includes bibliographical references. / Introduction: Acute kidney injury results from a rapid decline in kidney function. There are many potential causes, some of which are preventable. It carries the risks of mortality, progression to chronic kidney disease and worsening of pre-existing chronic kidney disease. There is a scarcity of data on the epidemiology of acute kidney injury in sub-Saharan Africa. The aims of this study were to describe the epidemiology of acute kidney injury at Groote Schuur hospital, and factors associated with mortality and renal recovery. Methods: This was a prospective observational study of patients with acute kidney injury, referred to Groote Schuur Hospital Renal Unit from the 8th of July 2012 to the 8th of July 2013. Ethics approval was granted by the University of Cape Town Human Research Ethics Committee. We excluded patients younger than 13 years, kidney transplant patients, and those not fulfilling the consensus definition of acute kidney injury according to the Kidney Disease: Improving Global Outcomes (KDIGO) group. Data on patient demographics, medical history, clinical observations, investigations, and cause of acute kidney injury was collected from a clerking sheet designed for the study. Patients were followed up at, or after 3 months (90 days) for assessment of survival and renal recovery. The main outcomes were recovery of renal function and mortality at 3 months. Data was entered into an Excel spreadsheet, and imported onto Stata 12.1 for analysis. Results: A total of 366 patients were included. The median age was 44 years (IQR 14-82). Of these 214 were male (58.5%). Referrals were from medical, surgical and obstetrics and gynaecology departments. The majority, 217 (59.3%) were medical referrals. Most, 265 (72.4%) had community acquired acute kidney injury. The majority of the 101 patients with hospital acquired acute kidney injury, 72 (71.3%) had severe, stage 3 acute kidney injury. Hypertension was the commonest co-morbidity, present in 152 (41.5%) of the patients. There were 75 (20.6%) HIV positive patients. Acute tubular necrosis was the most common cause of acute kidney injury, identified in 251 (68.6%) patients. Renal biopsies were carried out in 36 (9.8%) patients. More than half, 202 (55.2%), of the patients were in the intensive care unit, while 204 (55.7%) were dialysed. Fluid input was recorded in 140 patients (38.3%). Overall 3 month mortality was 38.8% (142 patients). Of the 224 surviving patients, 119 (53.1%) had a follow up serum creatinine. Of these, 95 (80.5%) had full renal recovery, and 4 (3.4%) went on to end stage renal disease. On multivariate analysis, mechanical ventilation was strongly associated with mortality at 3 months (OR 2.46, p-value 0.0 19, 95% CI 1.41-4.03). Sepsis had a borderline significant association with 3 month mortality (OR 1.83, P-value 0.066, 95%CI 1.02 – 3.27), as did prolonged time to dialysis (OR 1.93, p-value 0.080, 95% CI 0.93 – 4.03). HIV was not associated with mortality on univariate analysis (OR 1.07, p-value 0.801, 95%CI 0.64-1.80). Conclusions: Acute kidney injury carries a high mortality risk, most significant in mechanically ventilated patients. Sepsis and, in those dialysed, late dialysis, may be associated with a high risk of mortality. Efforts to reduce hospital acquired acute kidney injury and to improve patient fluid balance chart records should be made.

Background: South Africa [SA] currently performs the most peritoneal dialysis [PD] in Africa. Yet, outcome data is limited. With the collision of epidemics of communicable and non-communicable diseases in Africa the need for chronic dialysis is escalating. PD remains a life-saving modality especially as haemodialysis is limited in the state sector. Methods: We retrospectively analysed all patients undergoing PD at Groote Schuur Hospital from January 2008 until June 2014 and thereafter prospectively until June 2015. Variables included demographics, adequacy, modality, fluid, cardiovascular risk and diabetes. The influences of these variables on peritonitis rate, technique and patient survival were assessed. Results: 230 patients were initiated on PD, 31 were excluded as they were on PD for < 90 days. The mean age was 39.7 +/- 10.4 years [SD], 49.8% were male and 63.8% were mixed ancestry. 9.8 % were diabetic at dialysis initiation. The average length of time on PD was 17 months (IQR 8 - 32). The peritonitis rate was 0.87 events per patient years. One, 2 and 5 year patient and technique survival was 94.4%, 84.3% and 60.2% and 82.5%, 69.0% and 37.4% respectively. Fluid overload (p=0.019) and low haemoglobin (p=0.001) were independent risk factors for poor survival. African race (HR 1.97, 95% CI (1.16 - 3.37) and fluid overload (p= 0.002) were both predictors of technique failure. Conclusions: In our PD-First programme the results are encouraging, despite lack of home visits due to safety, resource limitations and a high disease burden. Technique failure in African race needs further evaluation. Peritoneal dialysis remains a viable, life-saving alternative in an African setting.

Includes bibliographical references / BACKGROUND: Glomerulonephritis is a common cause of end-stage renal disease (ESRD) in developing countries. Idiopathic membranous nephropathy (IMGN) is an identified cause of nephrotic syndrome in South Africa. Early attainment of complete remission (CR) or partial remission (PR) in patients with IMGN has been shown to slow progression to ESRD. There is a dearth of outcome studies in Africa on IMGN. METHODS: This study was approved by the institution's Human Research Ethics Committee. It was a retrospective review of patients diagnosed (biopsy-proven) with IMGN at the Division of Nephrology and Hypertension, Groote Schuur Hospital, Cape Town, over a 10-year period. Secondary causes of MN were excluded in this study. Demographic, clinical, biochemical and histological records of such patients were retrieved for analysis. The trends in clinical and biochemical parameters over the course of follow-up from baseline were also determined. The primary outcome of interest was the attainment of a CR or PR at the last date of follow-up. Predictors of the composite of CR and PR at the last follow-up visit were assessed using univariate and multivariate Cox-Regression analysis. The trend in estimated glomerular filtration rate over the median duration of follow-up was evaluated as a secondary outcome. RESULTS: There were 56 patients with histologic and clinical parameters compatible with the diagnosis of IMGN. There were 26/56 females (46.4%) with an overall mean age of 41.5±14.6 years. Forty-three (43) patients had subsequent follow-up care at our centre with a median duration of follow-up of 23.0 (13.0, 48.0) months. Sixteen patients (37.2%) were treated with immunosuppression (ISP)-combination of steroids and cyclophosphamide, and 81.4% received renin-angiotensin system (RAS) blockade. There were no statistically significant differences in demographic and clinical features of patients treated with or without ISP. Trends in level of proteinuria, estimated GFR and serum albumin concentrations were also not significantly different between the two groups. Eighteen patients (41.9%) reached CR or PR at the last visit. There were also no statistically significant differences in demographic, clinical, histological, and biochemical characteristics of patients who had or had not achieved remission. The median time-to-remission of patients treated with or without ISP was similar - 48.6 and 48.7 months respectively (p=0.13) while the proportions of patients not reaching CR/PR at 1 year and 2 years were 94.6% and 80.8% respectively by Kaplan-Meier analysis. Gender, race and u se of immunosuppression did not influence remission status (log rank p>0.05). On regression analysis, the predictors of CR/PR at last follow up visit were GFR [OR 1.01 (95%CI: 1.00 - 1.02); p=0.041] and systolic BP (OR 0.97 [95%CI: 0.95 – 0.99); p=0.036]. CONCLUSION: Remission outcomes with the current immunosuppressive treatment protocol for I M G N are delayed and poor. There is a need for its re-evaluation and also for longitudinal, multicenter studies to assess the best treatment approach (-es) to IMGN in South Africa.

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.

Background: South Africa [SA] has a growing burden of chronic kidney disease [CKD], with limited health resources. Cape Town offers a PD-First policy due to both limitations on haemodialysis slots and cost saving measures. This study aimed to compare health related quality of life [HRQOL] between haemodialysis [HD] and peritoneal dialysis [PD], given the lack of autonomy in modality choice and socioeconomic challenges our patients face. Methods: This cross-sectional study was performed at Groote Schuur Hospital between July 2015 and December 2016. Demographic, socio-economic variables and perception of safety were collected. HRQOL was assessed using the Kidney Disease Quality of Life-Short Form [KDQOL-SFTM] version 1.3. All data was compared between the two dialysis modalities. Results: 77 HD patients and 33 PD patients were included in the study (Total n=110). There were no significant differences in demographics. The median age was 42.5 years [IQR: 32.4-48.6] and 57.3% were female. HD patients had less pain [p=0.036], better emotional well-being [p=0.020] and better energy/fatigue score [p=0.015]. Both cohorts experienced impairment in physical health, with PD having significant limitation [p=0.05]. The only significant symptoms in the renal domain was that PD experienced more shortness of breath [p=0.0001]. Overall, patients in both groups had very poor socio-economic circumstances. Safety was a major concern with the majority reporting feeling unsafe in their homes. Conclusions: The patients in our dialysis service have very challenging social circumstances with high rates of poverty and profound safety concerns. Patients on PD scored worse in 4 HRQOL domains, possibly due to a lack of autonomy in dialysis modality choice and less frequent contact with dialysis staff to provide encouragement and support. Additional psychological and social support needs to be instituted to help improve our patient's wellbeing on PD.

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)