Update on the Treatment of Glomerulonephritis in Adults in Low-to-Middle-Income Countries

Glomerular diseases are a common cause of chronic kidney disease in several low-to-middle-income countries (LMIC). Additionally, they represent up to 52% of patients with end-stage renal disease (ESRD) in Africa. Current guideline recommendations for the treatment of glomerular diseases may not always be applicable in LMIC due to various challenges related to disease diagnosis and the availability of medicines. A treatment approach that starts with disease diagnosis and proper use of adjuvant therapies mainly targeted at blood pressure and proteinuria reduction is an effective therapeutic option and is recommended for patients in LMIC with glomerular pathologies. The use of immunosuppressive therapies in adults with glomerular diseases should, as far as is possible, be guided by the histological diagnosis obtained through renal biopsy. Prednisone and cyclophosphamide still form the bulk of treatment for glomerular diseases in most countries. Due to the adverse effects associated with immunosuppression, prednisone and cyclophosphamide use must be carefully weighed against the risk of potential side effects, and there is a need for frequent monitoring to assess treatment efficacy, patient response, and adverse effects. It is not advisable to use immunosuppressive drugs (e.g., cyclosporine) that require monitoring of plasma levels in centres where such facilities are not available, given the possible associated nephrotoxicity. The purpose of this narrative review is to provide an update on the treatment of common glomerular diseases and to highlight simple approaches to treatment in LMIC. Knowledge of guideline recommendations on the treatment of various glomerular diseases will provide important understanding on useful therapeutic approaches

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

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

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

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. Summary: 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

Lupus nephritis: A simplified approach to diagnosis and treatment in South Africa

Lupus nephritis (LN) is a significant cause of morbidity and mortality in patients with systemic lupus erythematosus. Delayed recognitionand diagnosis of LN may be a common cause of chronic kidney disease among South Africans. Renal biopsy is the gold standard ofdiagnosing LN; however, this service is not available in many centres and the use of urinalysis, urine microscopic examination and otherserological tests can be useful in identifying patients with proliferative LN. Proliferative types of LN (class III, class IV and mixed class V)comprise the larger proportion of patients with this condition. Patients receiving immunosuppressive therapy need to be monitored closelyfor side-effects and drug-related toxicities. LN patients with end-stage renal disease (class VI) need to be prepared for renal replacementtherapy (dialysis and renal transplantation). In all patients, treatment should include adjunctive therapies such as renin angiotensinaldosterone system blockade, bone protection (with calcium supplements and vitamin D), blood pressure control and chloroquine – all ofwhich help to retard the progression of kidney disease

Demographic features of patients in included studies.

<p>Demographic features of patients in included studies.</p

Frequencies of glomerular diseases by African regions.

<p>Frequencies of glomerular diseases by African regions.</p

Regional differences (North Africa vs sub-Saharan Africa) in the prevalence of GNs.

<p>This figure shows the regional differences in the prevalence of primary GNs (4A) and secondary GNs (4B) for North Africa and sub-Saharan Africa.</p