Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans.

BACKGROUND: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. METHODS: This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. RESULTS: Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). CONCLUSION: Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.

Preventing CKD in Low- and Middle-Income Countries: A Call for Urgent Action.

The epidemiologic transition occurring in low- and middle-income countries (LMICs) has led to a surge in chronic kidney disease (CKD) prevalence because of a combination of highly prevalent chronic noncommunicable diseases (NCDs) and communicable diseases (CDs). The progressive rise in CKD prevalence in LMICs threatens the existing weak health systems in these countries as care for advanced CKD remains largely unavailable and unaffordable. An interplay of low literacy levels, poor health-seeking behavior, inadequate health care funding, weak health systems, and lack of skilled nephrology workforce has made it difficult for adequate CKD preventive measures to be implemented. Primary, secondary, and tertiary prevention measures need to be instituted in LMICs by a collaboration of governmental and nongovernmental organizations to stem this tide and help prevent deaths from other NCDs that share similar risk factors with CKD. For these to be effective, locally relevant knowledge is needed to contextualize existing prevention and control solutions, or to develop novel and more appropriate solutions for LMICs.

Integration of Care in Management of CKD in Resource-Limited Settings.

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.

Association Between Telomere Length, Chronic Kidney Disease, and Renal Traits: A Systematic Review.

Telomere length (TL) is an important biological variable that can influence a variety of disease-related complex traits as well as host-environment interactions such as drug and nutritional responses. Chronic kidney disease (CKD) is a common global health challenge especially with the currently aging world population. We conducted a PubMed database search according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines for systematic reviews. Studies in adults (18 years and above) in which TL was determined and correlated with CKD, renal traits, and function were included, while animal model studies were excluded. Nine studies comprising 7829 participants, published between 2005 and 2016, met the inclusion criteria. These included eight observational studies (six being prospective), and one clinical trial. Participants in two studies were diabetic patients with varying stages of CKD, and nondialysis chronic glomerulonephritis CKD patients in two other studies. TL measurements used polymerase chain reaction in five studies, terminal restriction fragmentation in three studies, and quantitative fluorescence in situ hybridization in one study. Short TL was independently associated with increased risk of prevalent microalbuminuria in diabetic men with CKD (p = 0.007). Among CKD patients with heterogeneous etiologies, however, there was an unadjusted lower risk (p < 0.001). Short TL was significantly associated with CKD progression among smokers (p = 0.001) and diabetic patients (p = 0.03). On the other hand, long TL was paradoxically associated with longer diagnosed duration of moderate CKD. We postulate that shortening TL might be associated with CKD prevalence/occurrence or declining kidney function, but this association is likely offset by the cellular telomere reparative process in those surviving longer with CKD. This systematic review underscores the need for future omics and human genetics research to delineate the contribution of TL to CKD, renal dysfunction, and related health outcomes. Telomeres and telomerase activity hold great promise for CKD risk stratification and personalized medicine.

A practical approach to the nutritional management of chronic kidney disease patients in Cape Town, South Africa.

BACKGROUND: The multi-racial and multi-ethnic population of South Africa has significant variation in their nutritional habits with many black South Africans undergoing a nutritional transition to Western type diets. In this review, we describe our practical approaches to the dietary and nutritional management of chronic kidney disease (CKD) patients in Cape Town, South Africa. DISCUSSION: Due to poverty and socio-economic constraints, significant challenges still exist with regard to achieving the nutritional needs and adequate dietary counselling of many CKD patients (pre-dialysis and dialysis) in South Africa. Inadequate workforce to meet the educational and counselling needs of patients, inability of many patients to effectively come to terms with changing body and metabolic needs due to ongoing kidney disease, issues of adherence to fluid and food restrictions as well as adherence to medications and in some cases the inability to obtain adequate daily food supplies make up some of these challenges. A multi-disciplinary approach (dietitians, nurses and nephrologists) of regularly reminding and educating patients on dietary (especially low protein diets) and nutritional needs is practiced. The South African Renal exchange list consisting of groups of food items with the same nutritional content has been developed as a practical tool to be used by dietitians to convert individualized nutritional prescriptions into meal plan to meet the nutritional needs of patients in South Africa. The list is currently utilized in counselling CKD patients and provides varied options for food items within the same group (exchangeable) as well as offering ease for the description of suitable meal portions (sizes) to our patients. Regular and continuous education of CKD patients by a multi-disciplinary team in South Africa enables our patients to meet their nutritional goals and retard CKD progression. The South African renal exchange list has proved to be a very useful tool in meeting this need.

Baseline Predictors of Mortality among Predominantly Rural-Dwelling End-Stage Renal Disease Patients on Chronic Dialysis Therapies in Limpopo, South Africa.

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.

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.