Browsing by Author "Fabian, June"

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    Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations
    (2022-06) Jean-Tristan Brandenburg; Melanie A. Govender; Winkler, Cheryl A.; Boua, Palwende Romuald; Agongo, Godfred; Fabian, June; Ramsay, Michèle
    Background and objectives: Recessive inheritance of African-specific APOL1 kidney risk variants is associated with higher risk of nondiabetic kidney disease, progression to kidney failure, and early-onset albuminuria that precedes eGFR decline. The effect of APOL1 risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine APOL1 risk allele prevalence and associations between APOL1 genotypes and kidney disease in West, East, and South Africa. Design, setting, participants, & measurements: This cross-sectional population-based study in four African countries included 10,769 participants largely aged 40-60 years with sociodemographic and health information, anthropometry data, and blood and urine tests for biomarkers of kidney disease. APOL1 risk alleles were imputed from the H3Africa genotyping array, APOL1 risk allele and genotype frequencies were determined, and genetic associations were assessed for kidney disease. Kidney disease was defined as the presence of eGFR <60 ml/min per 1.73 m2, albuminuria, or a composite end point including eGFR <60 ml/min per 1.73 m2 and/or albuminuria. Results: High G1 allele frequencies occurred in South and West Africa (approximately 7%-13%). G2 allele frequencies were highest in South Africa (15%-24%), followed by West Africa (9%-12%). Associations between APOL1 risk variants and albuminuria were significant for recessive (odds ratio, 1.63; 95% confidence interval, 1.25 to 2.12) and additive (odds ratio, 1.39; 95% confidence interval, 1.09 to 1.76) models. Associations were stronger for APOL1 G1/G1 genotypes versus G0/G0 (odds ratio, 3.87; 95% confidence interval, 2.16 to 6.93) compared with either G2/G2 (odds ratio, 1.65; 95% confidence interval, 1.09 to 2.51) or G1/G2 (odds ratio, 1.24; 95% confidence interval, 0.83 to 1.87). No association between APOL1 risk variants and eGFR <60 ml/min per 1.73 m2 was observed. Conclusions: APOL1 G1 and G2 alleles and high-risk genotype frequencies differed between and within West and South Africa and were almost absent from East Africa. APOL1 risk variants were associated with albuminuria but not eGFR <60 ml/min per 1.73 m2. There may be differential effects of homozygous G1 and G2 genotypes on albuminuria that require further investigation.
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    Data Set : Prevalence, characterization and response to chronic kidney disease in an urban and rural setting in South Africa
    (2016-11-18) Naicker, Saraladevi; Fabian, June; Jaya A George; Harriet R Etheredge; Manuel van Deventer; Robert Kalyesubula; Alisha N Wade; Laurie A Tomlinson; Stephen Tollman
    Globally, chronic kidney disease (CKD) is an emerging public health challenge but accurate data on its true prevalence are scarce, particularly in poorly resourced regions such as sub-Saharan Africa (SSA). Limited funding for population-based studies, poor laboratory infrastructure and the absence of a validated estimating equation for kidney function in Africans are contributing factors. Consequently, most available studies used to estimate population prevalence are hospital-based, with small samples of participants who are at high risk for kidney disease. While serum creatinine is most commonly used to estimate glomerular filtration, there is considerable potential bias in the measurement of creatinine that might lead to inaccurate estimates of kidney disease at individual and population level. To address this, the Laboratory Working Group of the National Kidney Disease Education Program published recommendations in 2006 to standardize the laboratory measurement of creatinine. The primary objective of this review was to appraise implementation of these recommendations in studies conducted in SSA after 2006. Secondary objectives were to assess bias relating to choice of estimating equations for assessing glomerular function in Africans and to evaluate use of recommended diagnostic criteria for CKD. This study was registered with Prospero (CRD42017068151), and using PubMed, African Journals Online and Web of Science, 5845 abstracts were reviewed and 252 full-text articles included for narrative analysis. Overall, two-thirds of studies did not report laboratory methods for creatinine measurement and just over 80% did not report whether their creatinine measurement was isotope dilution mass spectroscopy (IDMS) traceable. For those reporting a method, Jaffe was the most common (93%). The four-variable Modification of Diet in Renal Disease (4-v MDRD) equation was most frequently used (42%), followed by the CKD Epidemiology Collaboration (CKD-EPI) equation for creatinine (26%). For the 4-v MDRD equation and CKD-EPI equations, respectively, one-third to one half of studies clarified use of the coefficient for African-American (AA) ethnicity. When reporting CKD prevalence, <15% of studies fulfilled Kidney Disease: Improving Global Outcomes criteria and even fewer used a population-based sample. Six studies compared performance of estimating equations to measured glomerular filtration rate (GFR) demonstrating that coefficients for AA ethnicity used in the 4-v MDRD and the CKD-EPI equations overestimated GFR in Africans. To improve on reporting in future studies, we propose an 'easy to use' checklist that will standardize reporting of kidney function and improve the quality of studies in the region. This research contributes some understanding of the factors requiring attention to ensure accurate assessment of the burden of kidney disease in SSA. Many of these factors are difficult to address and extend beyond individual researchers to health systems and governmental policy, but understanding the burden of kidney disease is a critical first step to informing an integrated public health response that would provide appropriate screening, prevention and management of kidney disease in countries from SSA. This is particularly relevant as CKD is a common pathway in both infectious and non-communicable diseases, and multimorbidity is now commonplace, and even more so when those living with severe kidney disease have limited or no access to renal replacement therapy.
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    Preformulation and formulation study of dexchlorphenniramine maleate for use in the development of a new sustained release dosage form
    (1994-03) Fabian, June
    Preformulation and formulation study of dexchlor- pheniramine maleate (DCPM) for it's inclusion into a gelforming sustained release dosage form was investigated. A modification of the USP apparatus 2 is proposed as an alternative to currently recommended USP dissolution apparatus for floating, gelforming drug delivery systems. In addition, the role of magnesium stearate and talc as dissolution retardants in controlled release matrix tablets is investigated, through application of a factorial design.
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    Prevalence and characterisation of chronic kidney disease in a rural setting in South Africa
    (2021) Fabian, June
    Introduction: In South Africa (SA) and Sub-Saharan Africa (SSA), the burden of chronic kidney disease (CKD) is unknown, associated risk is poorly characterised, and equations to estimate glomerular filtration rate (eGFR) have limited validation. This study aimed to determine the population prevalence of CKD, identify associated risk factors, and measure kidney function using iohexol (mGFR) as the reference for comparing eGFR equations. If inaccurate, a model would be developed to better predict eGFR, therefore more accurately determining CKD burden. Methods: The research was conducted in the MRC/Wits-Agincourt Unit, Bushbuckridge, Mpumalanga Province. To determine population prevalence of CKD and associated risk, 2 021/2 759 adults, aged 20 to 80 years were recruited (prevalence of CKD negligible in those younger than 20). CKD prevalence was determined by measuring albuminuria (albumin: creatinine ratio (ACR)≥3mg/mmol) and estimating GFR (eGFR<60ml/min/1.73m2), using the CKD-EPI (creatinine) equation without ethnicity coefficient. CKD was confirmed with repeat screening after three months. Genotyping determined APOL1 renal risk variants. To measure GFR, a subsample of ~1 000 adults were recruited, stratified by eGFR and sex. Serum creatinine, cystatin C and GFR were measured using the slope-intercept method for iohexol plasma clearance (mGFR). eGFR equations were compared to mGFR, a new eGFR quation was modelled and validated, and multiple imputation modelling trained on mGFR was used to predict CKD. Data was pooled with Malawi and Uganda for analysis. Results: In SA, the WHO age standardised population prevalence of CKD was 4.0% (95% CI 3.1-4.9). Risk factors comprised high risk APOL1 genotypes (OR 1.95; 95% CI 1.20- 3.17); hypertension (OR 3.34; 95% CI 1.92-5.79); diabetes (OR 3.28 95% CI 1.61-6.70), HIV infection (OR 1.89; 95% CI 1.18-3.03) and hyperuricaemia (OR 1.85; 95% CI 1.13-3.05). Pooled data for mGFR included 2 578 of 3 025 participants. Overall and by country, creatinine-based equations overestimated kidney function compared to mGFR. The greatest bias occurred at low kidney function, where the proportion with mGFR <60ml/min/1.73m2 was more than double that estimated from creatinine. A new model for estimating GFR did not outperform existing equations, and no eGFR equation achieved the benchmark of estimated GFR within ±30% of mGFR for ≥75% of participants. Imputation modelling estimated prevalence of kidney disease as two- to three-fold higher than creatinine-based estimates across six SSA countries. Conclusion: In South Africa, CKD is prevalent and associated with high risk APOL1 genotypes, HIV infection and cardiometabolic diseases. In Sub-Saharan Africa, estimating GFR using serum creatinine substantially underestimated individual and population-level burdens of CKD, and cystatin C may be a preferable biomarker. Our findings have implications for individual care and public health policy, supporting implementation of screescreening for early detection and prevention of progression of CKD in those who are at risk.
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    Proteinuria in HIV seropositive individuals
    (2009-05-08T11:29:59Z) Fabian, June
    ABSTRACT This study was designed to screen antiretroviral therapy (ART)-naïve human immunodeficiency virus (HIV) infected patients for proteinuria, using urine dipsticks, at the HIV outpatient clinic at Johannesburg Hospital in an attempt to detect and treat early renal disease. In those with persistent proteinuria, a marker of kidney disease, renal biopsy was performed, ART with and without angiotensin-converting enzyme inhibitors (ACE-I) was initiated and patients were followed up for immunological and renal responses. After a minimum period of 12 months, a repeat biopsy was performed, where possible, to determine whether the histological lesions had responded to treatment. During urinary screening, proteinuria, leucocyturia and microscopic haematuria were common. Sterile leucocyturia may be associated with co-morbid sexually transmitted infection or tuberculosis. In the group that underwent renal biopsy with treatment, the renal and immunological response, before and after ART was highly statistically significant. Renal and immunological responses to ART were assessed by reduction in proteinuria with increased GFR, increased CD4 count with reduction in HIV viral load, respectively. On biopsy, HIV-associated immune complex disease was more common than HIVAN, a finding that contradicts international and some local data. Resolution of proteinuria was relatively rapid in comparison to the histological response to treatment, an effect not previously shown. This is the first study of its kind, to the author’s knowledge, that prospectively evaluates the effect of ART with/ ACE-I in ART-naïve HIV infected patients with both clinicopathological and histological criteria. It has shown unequivocally, that renal disease, particularly if detected and treated early in HIV infection, is responsive to treatment. These findings suggest screening for early detection and treatment of HIV-associated renal disease should be mandatory in HIV clinics in South Africa.