Metabolic syndrome, the leptin gene and kidney disease in non-diabetic black South Africans

Includes abstract.Includes bibliographical references (leaves 226-256).Obesity is a worldwide problem and is a factor in the pathogenesis of the metabolic syndrome and kidney disease through the development of obesity-related hypertension and neurohormonal mechanisms that include the action of leptin. As there appear to be no focussed studies that have looked at the association of the LEP gene with kidney disease phenotypes or cardiovascular disease markers like hypertension, the metabolic syndrome and obesity, and especially so in native black Africans, this study sought to establish an association between the obesity gene (LEP) and kidney disease phenotypes (independent of diabetes and hypertension) in a homogenous black African population

Update on the role of candesartan in the optimal management of hypertension and cardiovascular risk reduction

Hypertension is the most prevalent cardiovascular disease of adults and is a major risk factor for cardiovascular (CV) and cerebrovascular morbidity and mortality worldwide. Treatment of hypertension leads to reduction of CV morbidity and mortality through blood pressure reduction. The role of renin–angiotensin–aldosterone system (RAAS) in the pathophysiology of hypertension is mainly through generation of potent vasoconstrictor angiotensin II, stimulation of aldosterone secretion, and increase in sympathetic activation. Angiotensin II receptor blockers such as candesartan, a long-acting agent, alter this system by blocking the activation of angiotensin I receptors. Several important clinical trials have tested the efficacy of candesartan with placebo, antihypertensive agents, or other agents that block the RAAS for the control of hypertension and reduction of key CV risk factors such as microalbuminuria, heart failure, retinopathy, and carotid intima medial thickness. Candesartan has been shown to be a well-tolerated and effective antihypertensive agent with positive metabolic characteristics and additional benefits on CV and cerebrovascular outcomes. The aim of this review is to discuss the pharmacology, efficacy, and safety of candesartan, with an overview of key hypertension and CV studies involving candesartan

Lupus nephritis is associated with poor pregnancy outcomes in pregnant SLE patients in Cape Town: a retrospective analysis

Introduction: Systemic lupus erythematosus (SLE) is a multi-system auto-immune disease common in females of child-bearing age. The effect of pregnancy on SLE and vice versa have not been well characterised in Africans. The aim of this study is to describe the pregnancy outcomes of patients with SLE presenting to the maternity department of Groote Schuur Hospital, Cape Town.Methods: This study was designed as a retrospective review of records of pregnant women known with SLE and followed-up at the maternity section of Groote Schuur Hospital. The duration of survey was from the 1st January 2003 to 31st December 2013. Results: There were 61 pregnancies reviewed in 49 patients; 80.3% of the pregnancies were in patients of mixed ancestry and the rest (19.7%) in black African patients. The mean age at presentation of the current pregnancy was 27.2±5.0 years. Mean gestational age at presentation and delivery was 13.0 ± 6.0 weeks and 28.9 ± 9.8 weeks respectively and 47.5% of the pregnancies were in patients with lupus nephritis (LN). Thirty nine (63.9%) pregnancies reached the third trimester and 11.5% of all pregnancies ended in the first trimester. There was a lower number of live births to mothers of African ancestry than to those of mixed ancestry (p=0.001). In 55.7% of the pregnancies, no flare was reported while a renal flare was reported in 23%. Pregnancies in patients with LN had higher frequencies of flares (58.6% vs 31.3%; p=0.032), pre-eclampsia (34.5% vs 12.5%; p=0.041), longer stay in hospital (12.0 ± 9.1 days vs 6.1 ± 5.1 days; p=0.004) and low birth weight babies (1.94 ± 1.02 kg vs 2.55±0.95 kg; p=0.046) than in patients without LN. Only 36 (59%) of the neonates were discharged home alive and of these 2 (5.6%) were to mothers of black African ancestry (p=0.001).Conclusion: Increased lupus activity in pregnant SLE patients may account for the increased deaths of neonates born to SLE mothers. Patients of black African descent and those with LN tend to have a poorer outcome. A multi-disciplinary approach to the management of SLE patients (of child-bearing age or pregnant) needs to be further assessed for better outcomes

A diverse array of genetic factors contribute to the pathogenesis of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease with variable clinical presentation frequently affecting the skin, joints, haemopoietic system, kidneys, lungs and central nervous system. It can be life threatening when major organs are involved. The full pathological and genetic mechanisms of this complex disease are yet to be elucidated; although roles have been described for environmental triggers such as sunlight, drugs and chemicals, and infectious agents. Cellular processes such as inefficient clearing of apoptotic DNA fragments and generation of autoantibodies have been implicated in disease progression. A diverse array of disease-associated genes and microRNA regulatory molecules that are dysregulated through polymorphism and copy number variation have also been identified; and an effect of ethnicity on susceptibility has been described.http://dx.doi.org/10.1186/1750-1172-8-2IS

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

H3Africa and the African life sciences ecosystem: building sustainable innovation

Interest in genomics research in African populations is experiencing exponential growth. This enthusiasm stems in part from the recognition that the genomic diversity of African populations is a window of opportunity for innovations in postgenomics medicine, ecology, and evolutionary biology. The recently launched H3Africa initiative, for example, captures the energy and momentum of this interest. This interdisciplinary socio-technical analysis highlights the challenges that have beset previous genomics research activities in Africa, and looking ahead, suggests constructive ways H3Africa and similar large scale science efforts could usefully chart a new era of genomics and life sciences research in Africa that is locally productive and globally competitive. As independent African scholars and social scientists, we propose that any serious global omics science effort, including H3Africa, aiming to build genomics research capacity and capability in Africa, needs to fund the establishment of biobanks and the genomic analyses platforms within Africa. Equally they need to prioritize community engagement and bioinformatics capability an d the training of African scientists on these platform s. Historically , the financial, technological, and skills imbalance between Africa and developed countries has created exploitative frameworks of collaboration where African researchers have become merely facilitators of Western funded and conceived research agendas involving offshore expatriation of samples. Not surprisingly, very little funding was allocated to infrastructure and human capital development in the past. Moving forward, capacity building should materialize throughout the entire knowledge co-production trajectory: idea generation (e.g., brainstorming workshops for innovative hypotheses development by African scientists), data generation (e.g., genome sequencing), an d high-through put data analysis an d contextualization . Additionally, building skills for political science scholarship that questions the unchecked assumptions of the innovation performers be they funders, scientists, and social scientists, would enable collective innovation that is truly sustainable, ethical, and robust

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