3. Electronic Theses and Dissertations (ETDs) - All submissions

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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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    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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    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.
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