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Healthcare systems in low-income and lower-middle income countries (LLMICs) face significant challenges in the provision of health services, for example, kidney care to the population. Although this is linked to several high-level factors such as poor infrastructure, socio-demographic and political factors, healthcare funding has often been cited as the major reason for the wide gap in availability, accessibility and quality of care between LLMICs and rich countries. With the steady rising incidence and prevalence of kidney diseases globally, as well as cost of care, LLMICs are likely to suffer more consequences of these increases than rich countries and may be unable to meet targets of universal health coverage (UHC) for kidney diseases. As health systems in LLMICs continue to adapt in finding ways to provide access to affordable kidney care, various empirical and evidence-based strategies can be applied to assist them. This review uses a framework for healthcare strengthening developed by the World Health Organization (WHO) to assess various challenges that health systems in LLMICs confront in providing optimal kidney care to their population. We also suggest ways to overcome these barriers and strengthen health systems to improve kidney care in LLMICs., (© 2021 Asian Pacific Society of Nephrology.)

Despite positive economic forecasts, stable democracies, and reduced regional conflicts since the turn of the century, Africa continues to be afflicted by poverty, poor infrastructure, and a massive burden of communicable diseases such as HIV, malaria, tuberculosis, and diarrheal illnesses. With the rising prevalence of chronic kidney disease and kidney failure worldwide, these factors continue to hinder the ability to provide kidney care for millions of people on the continent. The International Society of Nephrology Global Kidney Health Atlas project was established to assess the global burden of kidney disease and measure global capacity for kidney replacement therapy (dialysis and kidney transplantation). The aim of this second iteration of the International Society of Nephrology Global Kidney Health Atlas was to evaluate the availability, accessibility, affordability, and quality of kidney care worldwide. We identified several gaps regarding kidney care in Africa, chief of which are (i) severe workforce limitations, especially in terms of the number of nephrologists; (ii) low government funding for kidney care; (iii) limited availability, accessibility, reporting, and quality of provided kidney replacement therapy; and (iv) weak national strategies and advocacy for kidney disease. We also identified that within Africa, the availability and accessibility to kidney replacement therapy vary significantly, with North African countries faring far better than sub-Sahara African countries. The evidence suggests an urgent need to increase the workforce and government funding for kidney care, collect adequate information on the burden of kidney disease from African countries, and develop and implement strategies to enhance disease prevention and control across the continent., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Prevention and early detection of kidney diseases in adults and children should be a priority for any government health department. This is particularly pertinent in the low-middle-income countries, mostly in Asia, Africa, Latin America, and the Caribbean, where up to 7 million people die because of lack of end-stage kidney disease treatment. The nephrology workforce (nurses, technicians, and doctors) is limited in these countries and expanding the size and expertise of the workforce is essential to permit expansion of treatment for both chronic kidney disease and end-stage kidney disease. To achieve this will require sustained action and commitment from governments, academic medical centers, local nephrology societies, and the international nephrology community., (© 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: South Africa (SA) is an upper middle-income country with a human immunodeficiency virus (HIV) epidemic, an accelerated burden of non-communicable diseases, and a concurrent epidemic of tuberculosis. These con-ditions overwhelm a health system struggling under the pressure of restricted resources, including an insufficient workforce. Private practice has become more involved in the care of patients in the country but serves mainly those who are members of a Medical Aid. These Medical Aids will usually cover up to 100% of the costs for management of chronic kidney disease (CKD)., Summary: There are currently 2.3 nephrologists per million individuals, which is far lower than the global average and grossly inadequate to meet the nephrology care needs in SA. Covert chronic dialysis rationing has occurred in the public sector since the 1960s. However, the lack of formality triggered the formation of explicit rationing guidelines in one province. These guidelines have been ethically endorsed but not embraced nationally. The demand for hemodialysis (HD) has led some provinces to practicing "PD-First" programs. SA remains one of only 12 countries within Africa that perform renal transplantation, and it is the only country in Africa that relies on deceased donation for the majority of its transplants. The first kidney transplant in SA took place at the University of the Witwatersrand, Johannesburg, in 1966 and the first dialysis was performed by a general practitioner working in a town close to Johannesburg in 1957. The University of Cape Town successfully pioneered the transplantation of kidneys from HIV-positive donors to positive recipients. SA was the second country in the world to form a National Kidney Foundation as well as a renal society. Nephrology training is in place and incorporates master's and PhD programs in nephrology. Despite the numerous challenges, SA nephrologists have been among the leading researchers in nephrology from the African continent.

Background: The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy., Methods: All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months., Results: Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m 2 vs. 47 mls/min/1.73m 2 , p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071)., Conclusions: In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required., Trial Registration: ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

HIV-positive individuals are at increased risk for kidney disease, including HIV-associated nephropathy, noncollapsing focal segmental glomerulosclerosis, immune-complex kidney disease, and comorbid kidney disease, as well as kidney injury resulting from prolonged exposure to antiretroviral therapy or from opportunistic infections. Clinical guidelines for kidney disease prevention and treatment in HIV-positive individuals are largely extrapolated from studies in the general population, and do not fully incorporate existing knowledge of the unique HIV-related pathways and genetic factors that contribute to the risk of kidney disease in this population. We convened an international panel of experts in nephrology, renal pathology, and infectious diseases to define the pathology of kidney disease in the setting of HIV infection; describe the role of genetics in the natural history, diagnosis, and treatment of kidney disease in HIV-positive individuals; characterize the renal risk-benefit of antiretroviral therapy for HIV treatment and prevention; and define best practices for the prevention and management of kidney disease in HIV-positive individuals., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The outcome of renal transplantation depends on achieving effective immunosuppression while minimising the consequences of such treatment. The occurrence of new-onset diabetes in the post-transplant period has been associated with several risk factors including some immunosuppressive medication. Better understanding of the clinical and genetic risk factors associated with new-onset diabetes after transplant (NODAT) could enable risk stratification of patients in the pre-transplant period, with the goal of applying measures that will reduce the incidence., Objectives: To ascertain the incidence of and clinical and genetic risk factors that predispose to NODAT, and to examine its effect on the outcome of renal transplantation., Methods: We performed a retrospective cohort review of all renal transplants at Groote Schuur Hospital, Cape Town, South Africa, between 2004 and 2008. Patients who were lost to follow-up or had pre-transplant diabetes or primary non-function were excluded. A subset of the cohort who gave informed consent was enlisted for genetic tests., Results: We identified 111 patients who met the inclusion criteria. The incidence of NODAT was 18.0% (n=20 patients). Risk factors for NODAT included age at transplant (p=0.03), body weight (p=0.04), treatment for acute cellular rejection (p=0.02) and polycystic kidney disease as the cause of renal failure (p=0.005). None of the genes investigated (TCF7L2 rs11196205, rs12255372 and rs7903146 and HNF1β rs1800575, rs121918671 and rs121918672) was found to be significantly associated with the risk of NODAT. The genotype frequencies for the single-nucleotide polymorphisms studied were closer (although not identical) to those reported for Caucasians than to those reported for the Yoruba (black) population in West Africa. Overall patient survival was 78% at five years, while graft survival was 72%. There was no significant difference in patient or graft survival between the group with NODAT and the group without., Conclusions: NODAT was common in renal transplant recipients. Some risk factors predate transplant and could be used to risk-stratify patients to determine appropriate risk-reduction strategies. The genetic determinants for NODAT in this population may differ from those reported elsewhere. NODAT had no impact on patient or graft survival in this cohort.

The prevalence of noncommunicable diseases, including chronic kidney disease (CKD), continues to increase worldwide, and mortality from noncommunicable diseases is projected to surpass communicable disease-related mortality in developing countries. Although the treatment of CKD is expensive, unaffordable, and unavailable in many developing countries, the current structure of the health care system in such countries is not set up to deliver comprehensive care for patients with chronic conditions, including CKD. The World Health Organization Innovative Care for Chronic Conditions framework could be leveraged to improve the care of CKD patients worldwide, especially in resource-limited countries where high cost, low infrastructure, limited workforce, and a dearth of effective health policies exist. Some developing countries already are using established health systems for communicable disease control to tackle noncommunicable diseases such as hypertension and diabetes, therefore existing systems could be leveraged to integrate CKD care. Decision makers in developing countries must realize that to improve outcomes for patients with CKD, important factors should be considered, including enhancing CKD prevention programs in their communities, managing the political environment through involvement of the political class, involving patients and their families in CKD care delivery, and effective use of health care personnel., (Copyright © 2017 Elsevier Inc. All rights reserved.)

End Stage Kidney Disease (ESKD) is a public health problem with an enormous economic burden. In resource limited settings management of ESKD is often rationed. Racial and socio-economic inequalities in selecting candidates have been previously documented in South Africa. New guidelines for dialysis developed in the Western Cape have focused on prioritizing treatment. With this in mind we aimed at exploring whether the new guidelines would improve inequalities previously documented. A retrospective study of patients presented to the selection committee was conducted at Groote Schuur Hospital. A total of 564 ESKD patients presented between 1 January 2008 and 31 December 2012 were assessed. Half of the patients came from low socioeconomic areas, and presentation was late with either overt uremia (n = 181, 44·4%) or fluid overload (n = 179, 43·9%). More than half (53·9%) of the patients were not selected for the program. Predictors of non-acceptance onto the program included age above 50 years (OR 0·3, p = 0·001), unemployment (OR 0·3, p<0·001), substance abuse (OR 0·2, p<0·001), diabetes (OR 0·4, p = 0·016) and a poor psychosocial assessment (OR 0·13, p<0·001). Race, gender and marital status were not predictors. The use of new guidelines has not led to an increase in inequalities. In view of the advanced nature of presentation greater efforts need to be made to prevent early kidney disease, to allocate more resources to renal replacement therapy in view of the loss of young and potentially productive life.

Aim: Remission outcomes among patients with idiopathic membranous glomerulonephritis is unknown in Africa. We sought to determine remission outcomes in a cohort of South African adult patients with IMGN., Methods: This was a retrospective review of patients with biopsy-proven IMGN over a 10 year period. Secondary causes of MN were excluded. Demographic, clinical, biochemical and histological records were retrieved for analysis. The trends in biochemical parameters from baseline were determined. The primary outcome was the attainment of a complete or partial remission (CR / PR) at the last follow-up., Results: Fifty-six patients met the criteria for inclusion and 43 had subsequent follow-up care with a median duration of follow-up of 23.0 (13.0-48.0) months. Sixteen patients (37.2%) were treated with immunosuppression (corticosteroids and cyclophosphamide) and 81.4% received anti-proteinuric agents. There were no significant differences in demographic and clinical features of patients categorized by immunosuppression (ISP) use. Changes in level of proteinuria and estimated glomerular filtration rate (eGFR) were also not significantly different between the two groups. Eighteen patients (41.9%) reached CR or PR at the last visit. The median times-to-remission of patients according to ISP status were similar at 48.6 and 48.7 months respectively (P = 0.104) while the proportions of patients not reaching CR/PR at 12 and 24 months were 94.6% and 80.8% respectively. Gender and race did not predict remission status (P > 0.05). Predictors of CR/PR at last visit were eGFR [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 in this African IMGN cohort are delayed and poor., (© 2015 Asian Pacific Society of Nephrology.)

Background: Dialysis therapy for end-stage renal disease (ESRD) continues to be the readily available renal replacement option in developing countries. While the impact of rural/remote dwelling on mortality among dialysis patients in developed countries is known, it remains to be defined in sub-Saharan Africa., Methods: A single-center database of end-stage renal disease patients on chronic dialysis therapies treated between 2007 and 2014 at the Polokwane Kidney and Dialysis Centre (PKDC) of the Pietersburg Provincial Hospital, Limpopo South Africa, was retrospectively reviewed. All-cause, cardiovascular, and infection-related mortalities were assessed and associated baseline predictors determined., Results: Of the 340 patients reviewed, 52.1% were male, 92.9% were black Africans, 1.8% were positive for the human immunodeficiency virus (HIV), and 87.5% were rural dwellers. The average distance travelled to the dialysis centre was 112.3 ± 73.4 Km while 67.6% of patients lived in formal housing. Estimated glomerular filtration rate (eGFR) at dialysis initiation was 7.1 ± 3.7 mls/min while hemodialysis (HD) was the predominant modality offered (57.1%). Ninety-two (92) deaths were recorded over the duration of follow-up with the majority (34.8%) of deaths arising from infection-related causes. Continuous ambulatory peritoneal dialysis (CAPD) was a significant predictor of all-cause mortality (HR: 1.62, CI: 1.07-2.46) and infection-related mortality (HR: 2.27, CI: 1.13-4.60). On multivariable cox regression, CAPD remained a significant predictor of all-cause mortality (HR: 2.00, CI: 1.29-3.10) while the risk of death among CAPD patients was also significantly modified by diabetes mellitus (DM) status (HR: 4.99, CI: 2.13-11.71)., Conclusion: CAPD among predominantly rural dwelling patients in the Limpopo province of South Africa is associated with an increased risk of death from all-causes and infection-related causes.

Background and Aim: Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014., Materials and Methods: We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data., Results: Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50-4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2-22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3-21.1), mesangiocapillary GN (MCGN); 11.8% (9.2-14.6), crescentic GN; 2.0% (0.9-3.5) and IgA nephropathy 2.8% (1.3-4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0-18.4) and 7.7% (4.5-11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs., Conclusions: Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases; this could have a positive impact on chronic kidney disease evaluation and treatment in the African continent since most glomerulopathies are amenable to treatment.

There is a dearth of data on end-stage renal disease (ESRD) in Africa. Several national renal registries have been established but have not been sustainable because of resource limitations. The African Association of Nephrology (AFRAN) and the African Paediatric Nephrology Association (AFPNA) recognize the importance of good registry data and plan to establish an African Renal Registry. This article reviews the elements needed for a successful renal registry and gives an overview of renal registries in developed and developing countries, with the emphasis on Africa. It then discusses the proposed African Renal Registry and the first steps towards its implementation. A registry requires a clear purpose, and agreement on inclusion and exclusion criteria, the dataset and the data dictionary. Ethical issues, data ownership and access, the dissemination of findings and funding must all be considered. Well-documented processes should guide data collection and ensure data quality. The ERA-EDTA Registry is the world's oldest renal registry. In Africa, registry data have been published mainly by North African countries, starting with Egypt and Tunisia in 1975. However, in recent years no African country has regularly reported national registry data. A shared renal registry would provide participating countries with a reliable technology platform and a common data dictionary to facilitate joint analyses and comparisons. In March 2015, AFRAN organized a registry workshop for African nephrologists and then took the decision to establish, for the first time, an African Renal Registry. In conclusion, African nephrologists have decided to establish a continental renal registry. This initiative could make a substantial impact on the practice of nephrology and the provision of services for adults and children with ESRD in many African countries.

The complications of chronic kidney disease (CKD) are dyslipidaemia, hyperkalaemia, metabolic acidosis, anaemia, and bone and mineraldisorders. Dyslipidaemia may be treated with low-density lipoprotein-lowering agents. Statins are ineffective in stages 4 and 5 CKD, but areindicated for preventing the progression of disease in the earlier stages. Chronic acidosis has recently been shown to be a risk factor in theprogression of CKD renal dysfunction. Therefore, treatment is mandatory. Practically, this should consist of 1 - 2 heaped teaspoons of sodiumbicarbonate 2 - 3 times per day, which is an inexpensive and safe therapy that does not raise the blood pressure in spite of the increased sodiumlevel. Target levels of haemoglobin, according to international guidelines, are between 10 g/dL and 12 g/dL. The serum phosphate level is raisedin stage 4 CKD, and especially in stage 5 CKD, which is associated with coronary carotid and other vascular calcifications and may result inischaemic heart disease, myocardial infarction and stroke. A raised parathyroid hormone level (secondary hyperparathyroidism) is also a majorrisk factor for cardiovascular disease and is associated with increased hypertension and resistance to the treatment of CKD-associated anaemia.

Background and Aim: Mesangiocapillary glomerulonephritis (MCGN) is a common cause of chronic kidney disease in developing countries. Data on the renal outcome of patients with idiopathic MCGN is limited. The aim of this study is to investigate the outcome of patients with idiopathic MCGN presenting to the Groote Schuur Hospital (GSH) Renal Unit in Cape Town., Materials and Methods: A retrospective study of patients with idiopathic MCGN followed up at our clinic. Seventy-nine patients with no identifiable cause of MCGN were included for analysis. A composite renal outcome of persistent doubling of serum creatinine or end stage renal disease (ESRD) was used. Kaplan Meier survival and Cox regression analysis were used to assess survival and identify factors predicting the outcome., Results: The mean age at biopsy was 33.9±13.6 years and 41.8% were black. Mean duration of follow up was 13.5±18.8 months. Twenty-three patients (34.2%) reached the composite endpoint. Overall, median renal survival was 38.7±11.7 months (95% CI 15.7-61.8) with 2-year and 5-year renal survival of 61% and 40.3% respectively. No significant difference was found for renal survival between males and females, treatment or non-treatment with immunosuppression, presence or absence of crescents or histological type of MCGN (p>0.05). On univariate Cox-regression analysis, factors found to be associated with the outcome were the estimated glomerular filtration rate at biopsy (OR 0.97 [95%CI: 0.95-0.99], p<0.0001), black race (OR 3.03 [95%CI: 1.27-7.21], p = 0.012) and presence of interstitial fibrosis in the biopsy (OR 2.64 [95%CI: 1.07-6.48], p = 0.034). Age, systolic blood pressure and attaining complete or partial remission approached significant values with the endpoint., Conclusions: The outcome of idiopathic MCGN in Cape Town is poor and requires further prospective studies to improve our understanding of this common disease.

Unlabelled: ♦, Introduction and Aim: Continuous ambulatory peritoneal dialysis (CAPD) is not a frequently used modality of dialysis in many parts of Africa due to several socio-economic factors. Available studies from Africa have shown a strong association between outcome and socio-demographic variables. We sought to assess the outcome of patients treated with CAPD in Limpopo, South Africa. ♦, Methods: This was a retrospective study of 152 patients treated with CAPD at the Polokwane Kidney and Dialysis Centre (PKDC) from 2007 to 2012. We collected relevant demographic and biochemical data for all patients included in the study. A composite outcome of death while still on peritoneal dialysis (PD) or CAPD technique failure from any cause requiring a change of modality to hemodialysis (HD) was selected. The peritonitis rate and causes of peritonitis were assessed from 2008 when all related data could be obtained. ♦, Results: There were 52% males in the study and the average age of the patients was 36.8 ± 11.4 years. Unemployment rate was high (71.1%), 41.1% had tap water at home, the average distance travelled to the dialysis center was 122.9 ± 78.2 kilometres and half the patients had a total income less than USD ($)180 per month. Level of education, having electricity at home, having tap water at home, body mass index (BMI), serum albumin and hemoglobin were significantly different between those reaching the composite outcome and those not reaching it (p < 0.05). The overall peritonitis rate was 0.82/year with 1-year, 2-year and 5-year survival found to be 86.7%, 78.7% and 65.3% (patient survival) and 83.3%, 71.7% and 62.1% (technique survival). Predictors of the composite outcome were BMI (p = 0.011), serum albumin (p = 0.030), hemoglobin (p = 0.002) and more than 1 episode of peritonitis (p = 0.038). ♦, Conclusion: Treatment of anemia and malnutrition as well as training and re-training of CAPD patients and staff to prevent recurrence of peritonitis can have positive impacts on CAPD outcomes in this population., (Copyright © 2014 International Society for Peritoneal Dialysis.)

Nephrology is a 'Cinderella speciality', a disregarded area of health care, in Africa. Other health issues have relegated the treatment of kidney diseases to a low priority status, and the cost of treating the more common and widespread communicable diseases, financial mismanagement and corruption in many countries has sounded the death knell for expensive therapies such as dialysis. The communicable diseases that have devastated the health systems around Africa are tuberculosis and HIV/AIDS. Until recently, very little information was available on the impact of HIV on acute and chronic dialysis admissions. Patients with acute kidney injury (AKI) in most of Africa are seldom treated because of great distances to travel, lack of expertise, poverty and poor sustainable funding for health matters. An acute peritoneal dialysis (PD) programme has now been initiated in Tanzania but the sustainability of this project will be tested in the future. The International Society of Nephrology (ISN) has developed a training programme for nephrologists from developing countries, which may now be bearing fruit. A report from the sub-Saharan Africa region shows that the numbers of patients on dialysis and those diagnosed with chronic kidney disease (CKD) has increased significantly. Other ISN-sponsored programmes such as Continuing Medical Education activities for physicians and community screening projects have had far-reaching positive effects. Government funding for a dialysis programme is well established in South Africa, but this funding is limited so that the numbers accepted for public dialysis are restricted. Consequently in the Western Cape province of South Africa, a 'category system' has been formulated to attempt to cope with this unacceptable and restrictive ruling.

Aim: To report the long-term outcome and complication profile of South African patients with proliferative lupus nephritis (PLN)., Methods: A retrospective review of 66 patients with biopsy-proven PLN [58 diffuse proliferative LN (Class IV) and 8 focal proliferative LN (Class III)] under our care from January 1995 to December 2009 was done., Results: Thirty-three (50 %) patients reached the composite end point of doubling of serum creatinine, end-stage renal disease (ESRD) or death. The 5-, 10- and 15-year cumulative event-free survival rates were 54, 34 and 27 %, respectively. Variables associated with the composite end point were simultaneous diagnosis of SLE and LN (p = 0.048); elevated serum creatinine at onset (p = 0.009); elevated systolic blood pressure (SBP) (p < 0.001) and elevated diastolic blood pressure (DBP) (p < 0.001) on follow-up; and non-remission following induction therapy (p < 0.001). The 5-, 10- and 15-year renal survival rates in our patients were 63, 52 and 52 %, respectively. Hypertension at onset of LN (p = 0.037), nephrotic-range proteinuria (p = 0.033), eGFR < 60 ml/min/1.73 m(2) (p = 0.013) and lack of remission following induction therapy (p < 0.001) were all associated with development of end-stage renal disease (ESRD). Elevated SBP on follow-up (95 % CI 1.03-1.34, p = 0.017) was the only factor associated with composite end point while failure to achieve remission following induction therapy was the only factor associated with ESRD on multivariate analysis. Thirty-five (53 %) patients developed complications with persistent leukopenia, gastritis, sepsis, tuberculosis (TB) and herpes zoster being the leading complications. Ovarian failure occurred in 4 (11 %) patients., Conclusion: The 5-, 10 and 15-year event-free survival rates were 54, 34 and 27 % and failure to achieve remission following induction therapy predicted poor renal survival on multivariate analysis.

Chronic kidney disease (CKD) is a worldwide public health problem, and its treatment imposes a considerable burden on patients and their families. Limitations in everyday activity may worsen the situation and affect the health-related quality of life (HRQOL) of patients with CKD. There are no studies on the HRQOL of dialysis patients in South Africa. We assessed the HRQOL of patients undergoing hemodialysis (HD) and continuous ambulatory peritoneal dialysis (PD) attending the Groote Schuur Hospital renal unit by using the Kidney Disease Quality of Life-Short Form version 1.3 questionnaire. Baseline demographic and clinical details of the participants were recorded. Analysis was performed (unpaired t test and univariate analysis) to compare the HRQOL between HD and PD patients and to identify factors influencing HRQOL. The HRQOL was low but not significantly different between HD and PD patients. In PD patients, the use of erythropoiesis-stimulating agents (ESA) significantly contributed to the emotional well-being (r 2 = 0.267; P = 0.01) and alleviation of pain (r 2 = 0.073; P = 0.049); in HD patients also, ESA use was associated with emotional well-being (r 2 = 0.258; P <0.0001) as well as improvement in energy/fatigue (r 2 = 0.390; P <0.0001). Systolic and diastolic blood pressures significantly influenced cognitive function in PD patients (P <0.05). Parathyroid hormone level significantly influenced the physical functioning and energy/fatigue domains in HD patients (P <0.0001). Serum ferritin (r 2 = 0.441; P = 0.002) and level of hemoglobin concentration (r 2 = 0.180; P = 0.006) were significantly associated with the domain role emotional in PD and HD patients, respectively. Although HRQOL is low in dialysis patients in Cape Town, the factors that have been identified to be associated with these scores (such as anemia and hyperparathyroidism) if aggressively managed and corrected may assist in improving patients' HRQOL.

Background: Life expectancy is low in many African countries due to several factors including the ongoing HIV epidemic. However, the global increase in life expectancy has translated to more elderly patients living with chronic kidney disease (CKD). The patterns of kidney disease in the elderly have never been described from sub-Saharan Africa., Methods: This study was a retrospective study of 111 elderly patients (age ≥ 60 years) who had a renal biopsy performed at the Groote Schuur Hospital in Cape Town between 1st January 2000 and 31st December 2009., Results: The mean age of patients at time of biopsy was 66.3 ± 5.7 years (males: 66.4 ± 5.6; females: 66.3 ± 5.9 years). Primary glomerular diseases were seen in 38.7%, secondary glomerular diseases in 36.0%, tubulointerstitial diseases in 17.1% and diseases classified as miscellaneous in 8.1% of all patients. Nephrotic syndrome was the most common indication for the performance of a renal biopsy (48.6%). Membranous lomerulonephritis (MGN) was the most common type of disease observed (14.4%) and was significantly more frequent in males than in females (p = 0.029). Other common histological diagnoses included diabetes nephropathy (12.6%), chronic glomerulonephritis (5.4%), and lupus nephritis (4.5%). HIV associated nephropathy (HIVAN) was only seen in 1 patient (0.9%)., Conclusion: The patterns of renal disease currently seen in elderly South Africans closely resembles that reported from other countries but is at complete variance with the pattern reported in the general population of South Africa in which HIV plays a significant role.

Background: Two hundred and twenty-one HIV-positive renal biopsies were analysed from Groote Schuur Hospital to determine outcomes and prognostic indicators based on histology and clinical features., Methods: The histology findings were compared with patient demographics, clinical and renal parameters, mortality, CD4 count and date of commencing combined anti-retroviral therapy (cART). Follow-up was between 1 and 3.5 years., Results: We found a spectrum of renal histologies in HIV-positive patients of which HIV-associated nephropathy (HIVAN) was the most common histology. cART reduced the mortality in those with any feature of HIVAN by 57% [adjusted hazard ratio (AHR) 0.43, 95% confidence interval (CI) 0.22-0.85]. Of those patients with HIVAN who died, 79% died of renal failure as registered on their death certificate. Proteinuria and microcysts were shown to be poor prognostic indicators (AHR 1.36: 1.09-1.70 and 2.04: 1.24-3.37). In patients with HIVAN alone followed for up to 2 years on cART, estimated glomerular filtration rate remained stable and there was a trend towards decreased proteinuria. cART improved survival in patients with isolated immune complex disease., Conclusions: As mortality is improved in patients with any feature of HIVAN or isolated immune complex disease, cART should be initiated once any of these histological features are established. We believe the spectrum of disease that constitutes HIVAN needs to be more specifically defined. The ultimate outcome may be determined by the histological subtype.

Human immunodeficiency virus (HIV) infection started in Africa circa 1930. South Africa has the highest prevalence rate in the world. Although reports of HIV-associated nephropathy (HIVAN) appeared in the early 1980s, the earliest report from sub-Saharan Africa (SSA) came in 1994. Geographical, socioeconomic, political, and ethical factors have worked in concert to shape the character of HIV disease as it is seen in SSA. Political leaders within SSA have, through their actions, significantly contributed to the incidence of HIV infection. Black females, who often face cultural suppression and disadvantage, have a higher prevalence of HIV than males. Too few studies and outcomes data have bedeviled the statistics in SSA in relation to HIVAN prevalence and its management. Much of what is written is approximation and anecdotal. The largest reliable biopsy series comes from the University of Cape Town, where a workable classification of HIVAN has been developed to enable standardization of terminology. Histologic and clinical prognostic indicators with outcomes have been evaluated using this classification. Patients with HIV who present with acute kidney injury appear to have mainly acute tubular necrosis due to sepsis, dehydration, and nephrotoxic drugs. Since the rollout of combination antiretroviral therapy, the extent of HIV infection and kidney disease continues to be modified and possibly retarded., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The kidney is one of the major target organs affected by systemic lupus erythematosus. Although proliferative forms of lupus nephritis (LN) occur more frequently than membranous LN (MLN), the latter appears to have a more favourable outcome. Only a few studies have reported the outcome of patients with MLN., Methods: A retrospective analysis of patients with biopsy-confirmed MLN from a single centre in South Africa treated from 1st January 2000 to 31st December 2009., Results: The mean age of the patients (n = 42) at onset of LN was 35.0 ± 12.8 years with 73.8% of the patients being of mixed ancestry (coloureds). Eleven patients (26.2%) reached the composite end point of death or end-stage renal disease or persistent doubling of serum creatinine. The overall median survival and median renal survival times were 82.3 ± 15.5 months (95% confidence interval 52.0-112.6) and 84.5 ± 15.0 months (55.1-113.8), respectively. Also, 5-year event-free survival and renal survival were 64 and 71%, respectively. On multivariate analysis, systolic blood pressure (BP) during follow-up (P = 0.029), diastolic BP during follow-up (P = 0.020) and attainment of complete remission at 6 months (P = 0.033) were factors associated with the composite end points. Although treatment with chloroquine was not significantly associated with the composite end points (P = 0.05), we found that patients who received chloroquine had better renal survival compared with those who did not (P = 0.007)., Conclusions: The outcome of patients with MLN in Cape Town is poorer than for similar patients reported from other centres across the world. Better BP control may significantly influence outcome of disease in these patients.

Background: Due to poverty, many countries of sub-Saharan Africa suffer a severe burden of end-stage renal disease (ESRD), the cause of which is often unidentified. We sought to identify biopsy-proven causes of ESRD in Cape Town, South Africa, and to determine the outcome of these patients., Methods: Records of biopsies reported as ESRD over a 10-year period were selected for analysis. The demographic, clinical and biochemical characteristics of the patients at the time of biopsy were documented. The decision of the committee that assesses the eligibility of patients for long-term renal replacement therapy (RRT) was documented, and if a patient was not accepted the reasons for the rejection were noted., Results: Chronic glomerulonephritis (CGN) was the most frequent cause of ESRD (31.2%); human immunodeficiency virus-associated nephropathy (HIVAN) accounted for 12.5% of ESRD cases. Sixty-six patients (45.8%) were never reviewed by the assessment committee for placement in the dialysis program. Of the remaining 78 patients (54.2%) reviewed for RRT, only 48/78 (61.5%) were selected. A higher frequency of patients with HIVAN were not accepted for RRT (17.7%) than patients with HIVAN who were accepted (2.1%) (p=0.008). Social factors such as lack of housing, alcohol abuse, illicit drug abuse, lack of transportation and lack of family/social support accounted for 56.7% of patients not being accepted for RRT., Conclusion: There needs to be a development of programs amongst Africans to provide effective solutions that tackle the burden of ESRD, especially related to the increasing prevalence of HIVAN.

Background: Chronic kidney disease is a major public health problem in sub-Saharan Africa (SSA), which encompasses 70% of the least-developed countries in the world. Most people in SSA have no access to any form of renal replacement therapy (RRT). Given its ease of performance and patient independence, peritoneal dialysis (PD) should be an ideal form of RRT in SSA, but several complex and interdependent factors make PD a difficult option in SSA. The present review describes the practice of PD in SSA, with emphasis on Cape Town, South Africa., Methods and Results: After a review of the recent PubMed literature on RRT in SSA and an appraisal of nephrology practice in South Africa, factors that make the provision of RRT (especially PD) a challenge in SSA include the low number of qualified health care workers, socio-demographic issues (poor housing, electricity, and water supplies), and the cost of PD fluids in the region. Although South Africa has the largest PD population in all of SSA, the growth of PD in South Africa is specifically impeded by the system of RRT rationing, which favors HD; the methods of funding for dialysis and for remuneration of doctors in private practice; and many other socio-economic factors. The peritonitis rate remains relatively high, and it is a significant contributor to morbidity in PD patients in Cape Town., Conclusions: In many parts of SSA, PD could be the main dialysis modality. However, African governments must start taking responsibility for their people by providing adequate funds for renal replacement programs. Attempts to produce PD fluids locally and to train and educate health care workers will greatly improve the use of PD as a RRT option in SSA.

Background: Glomerular diseases, accompanied by nephrotic syndrome, contribute significantly to end-stage renal disease (ESRD) worldwide. We sought to show the distribution and frequency of biopsy-proven causes of nephrotic syndrome in native black Africans attending the Groote Schuur Hospital in Cape Town, South Africa., Methods: We retrospectively reviewed the biopsy data of 294 black South Africans with biopsy-proven cause of nephrotic syndrome in Cape Town over a 10-year period. Nephrotic proteinuria was accepted as urine protein excretion of at least 3.5 g in 24 hours. Glomerular diseases were classified into primary and secondary types. Serum creatinine concentrations were stratified into 3 levels to reflect the degree of renal dysfunction at the time of presentation. The frequency and distribution of disease were recorded according to age and gender., Results: Young adults (< or = 40 years of age) constituted 74.1% of the study population. Secondary glomerular diseases were more frequent (58.8%) and human immunodeficiency virus-associated nephropathy (HIVAN) was observed as the leading cause of nephrotic syndrome in both males and females (42.8%). Most patients with HIVAN (73.6%) presented for the first time with severe renal impairment and more than half of patients with non-HIVAN glomerular diseases presented with an abnormal serum creatinine. Of the primary glomerular diseases, mesangiocapillary glomerulonephritis was the commonest cause of the nephrotic syndrome (19.0%), while IgA nephropathy was the least common cause (1.7%)., Conclusions: HIVAN is a major cause of nephrotic syndrome in black South Africans and may be responsible for the rising incidence of ESRD in Africa.

The burden of renal disease in human immunodeficiency virus (HIV) and AIDS patients living in Africa is adversely influenced by inadequate socio-economic and health care infrastructures. Acute kidney injury in HIV-positive patients, mainly as a result of acute tubular necrosis, may arise from a combination of hemodynamic, immunological, and toxic insult. A variety of histopathological forms of chronic kidney disease is also seen in HIV patients; HIV-associated nephropathy (HIVAN) and immune complex disease may require different treatment strategies, which at present are unknown. The role of host and viral genetics is still to be defined, especially in relation to the different viral clades found in various parts of the world and within Africa. The arrival and availability of highly active antiretroviral therapy in Africa has given impetus to research into the outcome of the renal diseases that are found in those with HIV. It has also generated a new look into policies governing dialysis and transplantation in this group where previously there were none.

Aim: The development of lupus nephritis (LN) is associated with increased morbidity and mortality. In view of scarce data from South Africa on factors affecting renal outcome in LN, the authors' experience was reviewed to identify predictors of poor renal outcome., Methods: This is a retrospective review of 105 patients with biopsy-proven LN under our care from January 1995 to December 2007., Results: Forty-three (41.0%) patients reached the composite end-point of persistent doubling of the serum creatinine over the baseline value, development of end-stage renal disease (ESRD) or death during a mean follow-up period of 51.1 months (range 1-137 months). Baseline factors associated with the composite end-point included presence of systemic hypertension (P = 0.016), mean systolic blood pressure (SBP) (P = 0.004), mean diastolic blood pressure (DBP) (P = 0.001), mean serum creatinine (P = 0.001), estimated glomerular filtration rate (eGFR) (P = 0.003) and diffuse proliferative glomerulonephritis (World Health Organization class IV) (P = 0.024). Interstitial inflammation (P = 0.049), failure of remission in the first year following therapy (P < 0.001), the mean SBP on follow up (P < 0.001) and mean DBP on follow up (P < 0.001) were also associated with composite end-point. On multivariate analysis, baseline serum creatinine, non-remission following therapy (P = 0.038) and mean SBP on follow up (P = 0.016) were predictors of poor renal outcome., Conclusion: Baseline serum creatinine, failure of remission in the first year and mean SBP were predictors of poor renal outcome.

It is recognised that the metabolic syndrome promotes the development of cardiovascular disease. Although several studies have shown a relationship between the metabolic syndrome and kidney disease, few of these have used non-diabetic subjects, especially in the African population. This was a cross-sectional study of subjects of African origin, using the metabolic syndrome (MS) criteria of the National Cholesterol Education Program (NCEP) third Adult Treatment Panel (ATP III). Subjects with impaired fasting glucose, with two-hour glucose >or= 11.1 mmol/L after a glucose tolerance test, were excluded. Spot urine for albumin-to-creatinine ratio (ACR) was measured and the glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) equation. Microalbuminuria was defined as ACR between 3-30 mg/mmol. There was a significant decline in GFR and a significant increase in ACR with increasing number of MS traits. ACR increased four-fold between subjects with no MS traits and those with four or more traits. In subjects with the metabolic syndrome, there was a significant correlation between ACR and systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. Estimated GFR correlated significantly and inversely with body mass index (BMI) and serum leptin. These observations raise major clinical and public health concerns for developing countries, where both the metabolic syndrome and kidney disease are being reported more and more frequently. The potential economic impact is huge.

Metastatic calcification associated with renal failure is well described. Bone scanning agents accumulate to various degrees within extraskeletal sites of metastatic calcification. The authors describe a patient with polycystic kidney disease resulting in renal failure, with the subsequent development of secondary hyperparathyroidism and metastatic calcification. Bone scintigraphy revealed abnormal uptake in both lungs, the right leg, and the right hand.

Objective: To evaluate the efficacy and safety of Repotin, a locally produced recombinant human erythropoietin (rHuEPO), in the treatment of the anaemia of chronic renal failure (ACRF)., Design: The study consisted of two multicentre non-randomised open stages., Setting: Renal units at several teaching hospitals in South Africa., Participants: Haemodialysis patients with haemoglobin (Hb) levels less than 8.0 g/dl were recruited. The first stage examined 26 patients during a 12-week period in which the dose of intravenous rHuEPO was adjusted according to haematological response. In the second stage 27 patients were stabilised with intravenous rHuEPO and then maintained at a Hb level above 8.0 g/dl by subcutaneous administration for up to 1 year., Outcome Measures: In both stages, outcome was measured by clinical examination, blood pressure, full haematological parameters and blood chemistry., Results: In stage 1, all patients responded to therapy with a statistically significant increase in Hb from geometric means of 6.28 g/dl to 8.50 g/dl (geometric SDs of 1.17 and 1.20 respectively). The doses used ranged from 25 IU to 125 IU/kg (average 47.1). In the second stage, Hb levels reached a mean of 8.06 g/dl (SD 0.9) and were maintained at target range with an average dose of 55.5 IU/kg three times a week. Apart from changes in serum iron, ferritin (associated with increased haematopoiesis) and potassium, there were no significant alterations in blood chemistry. The incidence of adverse events reported during the 12-month second stage was no greater than that reported for other forms of rHuEPO therapy., Conclusion: Repotin is a safe and effective rHuEPO preparation for the treatment of ACRF.

Between January 1977 and October 1992, 6 patients who had undergone renal transplantation presented with a symptomatic lymphocele that failed to resolve after conventional therapy and eventually required surgical intervention. This complication developed between 7 and 36 months postoperatively. Patients presented with local discomfort combined with deteriorating graft function caused by ureteric obstruction. The lymphoceles recurred after aspiration or external drainage and resolved after omentopexy. We conclude that omentopexy is a satisfactory procedure for the treatment of lymphoceles which fail to resolve after aspiration or external drainage.

Twenty-two patients with chronic renal failure were randomly assigned to a conventional low-protein diet containing 0.6 g protein/kg/day or a very-low-protein diet containing 0.4 g protein/kg/day supplemented with essential amino acids; they were followed up for 9 months. There were no significant changes in body mass index, arm muscle area, percentage body fat, serum albumin and transferrin levels in any of the groups; neither was there any difference between the groups in respect of these parameters. Renal function, as measured by the reciprocal of serum creatinine over time, stabilised in both groups during intervention, with no significant difference between the groups. There was however no correlation between changes in renal function and changes in blood pressure, or dietary intake of protein, phosphorus, cholesterol, polyunsaturated and saturated fatty acids. There were also no significant changes and no significant differences between the groups in serum levels of parathyroid hormone and alkaline phosphatase, urine cyclic adenosine monophosphate, tubular reabsorption of phosphate, and the theoretical renal threshold for phosphate. The results of this study suggest that the supplemented very-low-protein diet was not superior to the conventional low-protein diet in terms of its effect on protein-energy status, renal function and biochemical parameters of renal osteodystrophy.

Study Objective: To determine the prevalence and presentation of mycobacterial infection as well as the influence on outcome in graft function and patient survival in renal transplant recipients at our institution., Design: A retrospective review of case records of all renal transplant recipients from 1980 to 1992., Setting: Groote Schuur Hospital, a large teaching hospital and regional tertiary referral center in Cape Town, South Africa., Patients: During the period reviewed, 857 transplants were performed. The records of 487 patients who had remained in Cape Town were examined., Results: There were 22 cases of mycobacterial infection (21 confirmed or presumed Mycobacterium tuberculosis and 1 unidentified Mycobacterium other than tuberculosis). In seven cases, immunosuppression had been intensified within 3 months of diagnosis. The median time from transplantation to diagnosis was 14 months (range, 2 to 74). Chest radiograph findings included consolidation (14), miliary pattern (4), pleural effusion (3), tuberculoma (2), cavitation (2), and hilar lymphadenopathy (1). Diagnosis of tuberculosis was made on sputum smears (eight), pleural biopsy specimen (two), fine-needle aspiration (one), and fiberoptic bronchoscopy in ten cases (brushings, eight; transbronchial biopsy specimen, three). Extrapulmonary tuberculosis (in addition to pulmonary tuberculosis) occurred in five patients (tuberculous meningitis, one; renal tuberculosis, one; and dissemminated infection, four). Five of the seven patients in whom immunosuppression had been intensified had concurrent infections; two of these died and the remainder returned to dialysis within 6 months. All but one patient received three antituberculosis drugs, including rifampin and isoniazid, for between 6 and 18 months. At the end of the period of review, 12 (59 percent) patients were alive, 10 with functioning grafts and 2 receiving dialysis. Four patients died while receiving antituberculosis treatment, but death was only directly related to tuberculosis in one case., Conclusions: Tuberculosis is an important infection in renal transplant recipients in Cape Town, but disseminated disease is less common than reported elsewhere.

Our previous studies indicate that impaired function of skeletal muscle limits the exercise tolerance of patients with end-stage renal failure who are either maintained on dialysis or undergo renal transplantation. To study the morphology of the condition, muscle biopsies were performed on eight patients with renal failure-associated myopathy. Control samples were taken from seven healthy athletes undergoing knee surgery and from five otherwise healthy but untrained subjects. Tissues were examined by routine light and transmission electron microscopy. Histochemical staining of frozen sections for myosin adenosine triphosphatase and quantitative computer-assisted morphometry of the fiber type and size was performed. The mean (+/- SD) size for type I fibers in patients was 61.2 +/- 11.8 microns, while type II fibers measured 46.7 +/- 11.4 microns. The mean percentage of type II fibers was 67% +/- 12%. These values are within the normal population range and were not different from controls. Significant changes were found on light microscopy of patient samples. These included fiber splitting, internalized nuclei, nuclear knots, moth-eaten fibers, fiber degeneration and regeneration, increased content of lipid droplets, and fiber-type grouping. Electron microscopy showed a large variety of nonspecific abnormalities, including mitochondrial changes, Z-band degeneration, myofilament loss, and accumulation of intracellular glycogen. Ten of 12 control subjects showed no such changes; minor abnormalities were noted on both light and electron microscopy in the remaining two subjects. Muscle oxidative capacity (19.5 +/- 5.1 microL O2/min) for patients with end-stage renal failure was not different from values for those who had undergone renal transplantation, but was lower than values found in trained athletes.(ABSTRACT TRUNCATED AT 250 WORDS)

Over a period of 6 years, 9 patients with diabetic nephropathy received renal allografts at Groote Schuur Hospital. This low figure represents 2.8% of the total number of renal transplants done at our institution, and is evidence of concern about the apparent poor results of transplantation in these patients. After 2 years, patients and graft survival rates in diabetics were 87% and 62% respectively. Vascular disease was a major problem. Six patients developed limb gangrene, and symptomatic coronary and cerebrovascular disease developed in 2 patients. Infections were common and included wound sepsis, cellulitis, candidiasis and urinary tract infections. Diabetes was poorly controlled after transplantation in 5 patients. Proliferative retinopathy was present in 6 patients but remained stable after transplantation. Despite very strict selection criteria, the results of renal transplantation in diabetic patients remain poor. Better treatment strategies are needed to justify acceptance of these patients for transplantation.

Whereas plasminogen activator of the tissue-type (t-PA) is present in extracts of kidney parenchyma, only small amounts of the enzyme can be detected in normal urine where the major plasminogen activator is of the urokinase-type (u-PA). These observations suggest the existence of physiological or anatomical barriers that effectively confine t-PA to renal tissue and exclude it from the urine. We examined the notion that disease might breach these barriers and so lead to the appearance of abnormal amounts of t-PA in the urine. Under the conditions of the simple fibrinolytic assay that we have developed, urine samples from 30 normal subjects did not contain detectable amounts of t-PA whereas we were able to demonstrate t-PA in samples from 43 of 65 patients with various forms of renal disease. When positive, therefore, tests for the presence of t-PA in human urine provide evidence for renal disease that may not otherwise be apparent.

Patients with bilateral renal carcinoma or malignancy in a solitary kidney are best managed by radical nephrectomy with subsequent dialysis and transplantation. Because of the risk of recurrence of the tumour, the timing of the transplant procedure is important. We report on two patients with bilateral renal carcinoma who were subjected to radical nephrectomy and then managed with dialysis and transplantation within 6 months.