The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa.

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/1.73m2 vs. 47 mls/min/1.73m2, 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.

Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

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.

Epidemiology of Histologically Proven Glomerulonephritis in Africa: A Systematic Review and Meta-Analysis.

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.

Out of Africa: Complete and partial remissions as a combined outcome in patients with idiopathic membranous glomerulonephritis in Cape Town.

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.

Outcome of patients with primary immune-complex type mesangiocapillary glomerulonephritis (MCGN) in Cape Town South Africa.

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.

Health-related quality of life in patients on hemodialysis and peritoneal dialysis.

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.

Long-term renal outcome and complications in South Africans with proliferative lupus nephritis.

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.

Kidney disease in elderly South Africans.

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.

The evolution of our knowledge of HIV-associated kidney disease in Africa.

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.

Outcome of patients with membranous lupus nephritis in Cape Town South Africa.

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.

Outcomes of rationing dialysis therapy in biopsy-proven end-stage renal disease in South Africa.

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.

Predictors of poor renal outcome in patients with biopsy-proven lupus nephritis.

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.

Nephrotic syndrome in adult black South Africans: HIV-associated nephropathy as the main culprit.

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.