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

Tuberculosis burden in stage 5 chronic kidney disease patients undergoing dialysis therapy at Livingstone Hospital, Port Elizabeth, South Africa

Background. Tuberculosis (TB) is currently the leading cause of death from a single infectious agent worldwide. Patients who receive dialysis are particularly vulnerable to TB infection owing to immune dysfunction. Nonetheless, there is a paucity of incidence data on dialysis patients infected with TB in high-burden countries, such as South Africa (SA).Objectives. To determine the incidence of TB in prevalent chronic kidney disease stage 5 (CKD-5D) patients on dialysis at a single centre in Eastern Cape Province, SA, and to identify the risk factors associated with TB infection.Methods. We conducted a retrospective cohort study of all consenting CKD-5D patients between April 2010 and March 2014 at Livingstone Hospital Renal Unit, Port Elizabeth, the Eastern Cape. TB was defined as definite or probable according to World Health Organization (WHO) criteria, and the cohort was split into those who developed TB (TB+) and those who did not (TB−).Results. One hundred and eleven patients were enrolled – predominantly black Africans (73%) and women (53%); the mean age (standard deviation (SD)) was 42 (9.8) years. The prevalence of HIV infection was 11%, all patients were receiving antiretroviral treatment and all had suppressed viral loads. Sixty-eight patients were on haemodialysis and 43 on peritoneal dialysis. Nineteen patients were diagnosed with 20 episodes of TB; 14 cases were pulmonary TB and 6 cases extrapulmonary TB. Of the patients with TB, 2 were HIV-infected, 7 (35%) were definite TB cases and 13 (65%) were probable cases. The calculated incidence rate was 4 505/100 000 patient years. Only informal housing (30% in TB+ v. 12% in TB−; p=0.042) and a history of hospitalisation (90% v. 76%, respectively; p=0.042) were significantly associated with a diagnosis of TB.Conclusions. Dialysis patients in the Eastern Cape region of SA are at extremely high risk of acquiring TB, with an incidence rate 4.1 times that of the local population and >5 times that of the general SA population. Only informal housing and a history of hospitalisation were identified as positive risk factors for TB in this young population with a low HIV prevalence. Isoniazid prophylaxis in this high-risk group might be of benefit, but further studies are required to inform such treatment

Global Sex Disparity Of Covid-19: A Descriptive Review Of Sex Hormones And Consideration For The Potential Therapeutic Use Of Hormone Replacement Therapy In Older Adults

The 2019-2020 SARS-related coronavirus-2 (SARS-CoV-2) pandemic has brought unprecedented challenges to healthcare sectors around the world. As of November 2020, there have been over 64 million confirmed cases and approaching 2 million deaths globally. Despite the large number of positive cases, there are very limited established standards of care and therapeutic options available. To date, there is still no Food and Drug Administration (FDA) approved vaccine for COVID-19, although there are several options in various clinical trial stages. Herein, we have performed a global review evaluating the roles of age and sex on COVID-19 hospitalizations, ICU admissions, deaths in hospitals, and deaths in nursing homes. We have identified a trend in which elderly and male patients are significantly affected by adverse outcomes. There is evidence suggesting that sex hormone levels can influence immune system function against SARS-CoV-2 infection, thus reducing the adverse effects of COVID-19. Since older adults have lower levels of these sex hormones, we therefore speculate, within rational scientific context, that sex steroids, such as estrogen and progesterone, needs further consideration for use as alternative therapeutic option for treating COVID-19 elderly patients. To our knowledge, this is the first comprehensive article evaluating the significance of sex hormones in COVID-19 outcomes in older adults

Report of the International Society of Hypertension (ISH) Hypertension Teaching Seminar organized by the ISH Africa Regional Advisory Group: Maputo, Mozambique, 2016

The International Society of Hypertension (ISH), in fulfilment of its mission of promoting hypertension control and prevention and also of advancing knowledge globally, organizes hypertension teaching seminars or ‘summer schools’ worldwide through the ISH Regional Advisory Groups. In Africa, seven of such seminars have been organized. This is a report of the eighth seminar held in Maputo, Mozambique, April, 2016. The seminar was attended by over 65 participants from 11 African countries. The Faculty consisted of 11 international hypertension experts. The eighth African hypertension seminar was a great success as confirmed by a pre- and post-test questionnaire

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

Polyarteritis nodosa presenting as a bladder outlet obstruction

Polyarteritis nodosa (PAN) of the urinary tract is rare. An unusual case of systemic PAN involving the bladder neck is described. A 27-year-old man, with known diastolic hypertension diagnosed 2 years earlier, was admitted with chronic urinary obstruction complicated by hydronephrosis. He had symptoms of myalgia and weight loss, was afebrile but had an elevated erythrocyte sedimentation rate and acute-on-chronic renal impairment. All virological and serological tests including hepatitis B and anti-neutrophil cytoplasmic antibody were negative. A computed tomography scan of the brain revealed small-vessel disease. A bladder neck mass was visualised on cystoscopy. Histological examination of this demonstrated a medium-sized necrotising vasculitis with small-vessel fibrinoid necrosis suggestive of PAN. At least six of the American College of Rheumatology criteria for PAN were met. The patient was treated with pulses of intravenous cyclophosphamide and oral corticosteroids with a good clinical response

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

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

Increasing access to integrated ESKD care as part of Universal Health Coverage

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle–income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide