Design and methods of the prevalence and pharmacogenomics of tenofovir nephrotoxicity in HIV-positive adults in south-western Nigeria study.

BACKGROUND: Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. Despite a safe renal profile in the clinical trials, long-term use of tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy although the underlying mechanisms remain undetermined. We aim to establish the prevalence of and risk factors for TDF-induced kidney tubular dysfunction (KTD) among HIV-I and II individuals treated with TDF in south-west Nigeria. Association between TDF-induced KTD and genetic polymorphisms in renal drug transporter genes and the APOL1 (Apolipoprotein L1) gene will be examined. METHODS: This study has two phases. An initial cross-sectional study will screen 3000 individuals attending the HIV clinics in south-west Nigeria for KTD to determine the prevalence and risk factors. This will be followed by a case-control study of 400 KTD cases and 400 matched controls to evaluate single nucleotide polymorphism (SNP) associations. Data on socio-demographics, risk factors for kidney dysfunction and HIV history will be collected by questionnaire. Blood and urine samples for measurements of severity of HIV disease (CD4 count, viral load) and renal function (creatinine, eGFR, phosphate, uric acid, glucose) will also be collected. Utility of urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) levels as surrogate markers of KTD will be evaluated. Genomic DNA will be extracted from whole blood and SNP analyses performed using the rhAMP SNP genotyping assays. Statistical analysis including univariate and multivariate logistic regression analyses will be performed to identify factors associated with KTD. DISCUSSION: In spite of TDF being the most commonly used antiretroviral agent and a key component of many HIV treatment regimens, it has potential detrimental effects on the kidneys. This study will establish the burden and risk factors for TDF-induced KTD in Nigerians, and explore associations between KTD and polymorphisms in renal transporter genes as well as APOL1 risk variants. This study may potentially engender an approach for prevention as well as stemming the burden of CKD in sub-Saharan Africa where GDP per capita is low and budgetary allocation for health is inadequate.

Spectrum of kidney diseases in Africa: malaria, schistosomiasis, sickle cell disease, and toxins.

Kidney diseases have assumed epidemic proportions in both developed and developing countries, particularly chronic kidney disease (CKD). While treatment modalities are available and accessible in developed economies with improvement in outcomes, survival, and quality of life, they are either unavailable or inaccessible in nations with emerging economies, particularly in sub-Saharan Africa (SSA), with an attendant worsening outcome and survival for CKD patients. The epidemiology of CKD in SSA has revealed that it preferentially affects adults in their economically productive years, usually below the age of 50 years, with consequent drain on the economy. This derives mainly from the major etiologies in the region, which are infection-induced chronic glomerulonephritis and hypertension, compounded by poverty as well as societal and health underdevelopment, poor resource allocation to health, and underdeveloped health infrastructures. This has made preventive nephrology a major goal in the sub-region, although those who have already developed CKD must be managed up to tertiary levels. In this review, we assessed the contributions of parasitic diseases (i.e., malaria and schistosomiasis), sickle cell disease and nephrotoxins with the aim of espousing their contributions to the burden of kidney disease, and proposing management options with the goal of ultimately reducing the burden of kidney disease in these disadvantaged populations.

Filter membrane-based automated therapeutic plasma exchange: a report of two cases from Nigeria.

These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility.

Association of Race with In-Hospital and Post-Hospitalization Mortality in Patients with Acute Kidney Injury.

INTRODUCTION: Acute kidney injury (AKI) is known to be associated with increased mortality, and racial differences in hospital mortality exist in patients with AKI. However, it remains to be seen whether racial differences exist in post-hospitalization mortality among AKI patients. METHODS: We analyzed data of adult AKI patients admitted to the University of Virginia Medical Center between January 1, 2001, and December 31, 2015, to compare in-hospital and post-hospitalization mortality among hospitalized black and white patients with AKI. Multivariable logistic regression analysis was used to analyze the association between race and in-hospital mortality, and 90-day post-hospitalization mortality among AKI patients that were discharged. Kaplan-Meier survival curve was used to evaluate long-term survival between black and white patients. RESULTS: Black patients had lower in-hospital mortality than white patients after adjusting for age, sex, estimated glomerular filtration rate, hospital length of stay, severity of AKI, comorbidities, and the need for dialysis and mechanical ventilation (odds ratio: 0.82; 95% confidence interval, 0.70-0.96, p = 0.0015). Similarly, at 90-day post-hospitalization, black patients had significantly lower adjusted odds of death than white patients (odds ratio: 0.64; 95% confidence interval, 0.46-0.93; p = 0.008). The median length of follow-up was 11.9 months (0.6-46.7 months). Kaplan-Meier survival curve showed that long-term survival was significantly better in black patients compared to white patients (median duration of survival; 39.7 vs. 24.8 months; p ≤ 0.001). CONCLUSIONS: Black patients with AKI had lower in-hospital mortality, 90-day post-hospitalization mortality, and better long-term survival rates compared to white patients with AKI.

Clinical presentation and outcome of autosomal dominant polycystic kidney disease in Nigeria.

INTRODUCTION: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is presumably rare in Africa. Knowledge about the disease in Nigeria is limited as demonstrated by scanty articles on the subject. OBJECTIVES: To determine the pattern of clinical presentation and outcome of ADPKD among ADPKD patients. METHOD: ADPKD subjects were prospectively studied between January 1996 and December 2010. Their demographics, clinical and investigation parameters were documented. Dependency on dialysis, renal transplant and death were the final outcomes. RESULTS: Forty one patients (M:F=1.3:1) with mean age of 48.6±4.6 years were studied. ADPKD was diagnosed at 2.73 cases per annum. Family history of ADPKD and hypertension were present in 56.1% and 82.9% respectively. Their mean systolic and diastolic blood pressures were 166.9 ±23.6 and 104 ±21.2 respectively.Nocturia (78.0%) and loin pain (68.3%) were the most common presenting symptoms. Liver cysts (31.7%) and aortic regurgitation (22.0%) were the predominant extra-renal manifestations.Twenty three (56.1%) received haemodialysis; no renal transplantation. Death rate was 51.2%. Presence of uraemia and intra-cerebral aneurysm contributed significantly to mortality. CONCLUSION: ADPKD may not be so rare in Nigeria. Awareness campaign to change attitude of family members to screening and further studies using newer criteria for diagnosis of ADPKD should be conducted.