Medicine

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Abnormal IgA1 O-glycosylation in a multi-ethnic population of IgA nephropathy patients in KwaZulu-Natal, South Africa.
(2013) Nansook, Prishani.; Assounga, Alain Guy Honore.
Background: The pathogenesis of IgA Nephropathy (IgAN) is poorly understood globally and curative therapy currently does not exist. Variable presentation among IgAN patients globally may be indicative of various underlying pathogenic mechanisms. Pathogenetic data on IgAN in Africa is scarce to nil. The current study provides the first O-glycosylation data for IgAN in South Africa or Africa. Methods: An enzyme-linked immunosorbent assay-type lectin binding assay was used to compare the serum IgA1 O-galactosylation in 19 IgAN patients and 20 controls. During 2007, 2009, and 2011, blood was extracted from consenting biopsy-diagnosed South African IgAN patients of African, Caucasian, Indian (predominantly) and mixed-race descent in KwaZulu Natal. The mean absorbance value corresponding to the degree of degalactosylation for the IgAN group was compared to that of the normal control group for each test. A non-parametric Wilcoxon matched-pairs test was used accordingly. The two-tailed p-value was used to assess for statistical significance between the groups. The low number of attending and consenting IgAN patients precluded IgA1 O-galactosylation analyses between race, gender, and disease stage. Results: The average means of the experiments for the IgAN group is 0.3678 ± 0.0790 (SEM) and is statistically significantly greater than the normal control group which is 0.2969 ± 0.0586 (SEM); (p = 0.0076). Conclusion: Thus, IgAN patients exhibited abnormal IgA1 O-glycosylation with a greater level of terminal degalactosylation of IgA1 in comparison to controls. Such a finding is consistent with other studies in Caucasian and Asian populations globally. Future specific therapeutic strategies that target the formation of abnormal glycosylation in IgA1 may be potentially beneficial in the study population.
Assessment of the immune response in kidney transplant patients.
(2009) Omarjee, Saleha.; Assounga, Alain Guy Honore.
Background: Management of a transplant recipient involves the use of multiple immunosuppressant drugs. Currently there is no test that reflects the overall immune status of the patient. This results in under or over suppression of the immune system and consequently increases in morbidity and mortality rates. Evaluation of the proliferative response of PBMC's to a mitogen PHA by measurement of intracellular ATP was evaluated as a tool to assess the immune response in kidney transplant patients. Method: PBMC's were separated from the blood samples of healthy controls and kidney transplant patients on cyclosporine, sirolimus, and tacrolimus based regimens by density gradient centrifugation, cells were counted and incubated overnight with and without PHA. The luciferin-Iuciferase enzyme reaction which induces bioluminescence and the Turner Biosystem luminometer were used to measure intracellular ATP levels in relative light units (RLU). An A TP standard curve was generated for each test. Results: The ATP (nglml) levels measured in the transplant recipients were lower and statistically significantly different (p< 0.0001) than the healthy controls. No statistically significant difference was measured between the cycIosporine and sirolimus drug groups. Patients on tacrolimus gave a statistically significant (p501 nglml ATP). Conclusion: Future studies to determine the predictive value of the A TP assay in directing immunosuppressive therapy are required. The assay described in this study is simple, sensitive and rapid and has possible application in immunological monitoring in a variety of conditions that affects the immune system. Keywords: kidney transplantation, immunosuppression, bioluminescence, lymphocyte, Adenosine Triphosphate (A TP), Phytohemmagglutinin (PHA)
The association between renal sonography and renal function in chronic kidney disease at Inkosi Albert Luthuli Chief Hospital: a retrospective descriptive study.
(2020) Frank, Astley Gershwyn.; Assounga, Alain Guy Honore.
Background Non-communicable diseases (NCDs) are rapidly emerging as a major cause of chronic kidney disease (CKD) in Africa with a reported prevalence of 10.7% locally. At current, few high-quality studies assessing the epidemiology of CKD in South Africa have been published. Alarmingly, CKD is now at epidemic proportions and is a leading cause of mortality with significant cost implications. This study aims to investigate economic means of predicting renal function in CKD by exploring the association between estimated glomerular filtration rate (eGFR) and renal morphology evaluated by ultrasound (US). Methods This is a retrospective descriptive chart review conducted at the Department of Nephrology, Inkosi Albert Luthuli Central Hospital (IALCH), Cato Manor, Kwa-Zulu Natal from January 2016 to December 2016. A total of 455 patients who had met the Kidney Disease Improving Global Outcomes (KDIGO) definition of CKD with eGFR (MDRD) and renal US performed were included. Demographic, clinical, laboratory and renal morphological data (renal length (RL), increased echogenicity (IE) and loss of corticomedullary differentiation (LCMD)) on US were collected and analyzed with SPSS software (v. 27). Associations between eGFR, parameters on US and CKD risk factors were determined using logistic regression analysis. Results Black Africans 75.2% (n.342) and females 56.9% (n.259) predominated the sample. Whilst, Indians, Whites and Coloureds comprised of 20.4%, 2.42% and 1.98% of the study respectively. The median age was 45.8 ± 14.3 years. Hypertension 34.9%, diabetes 26.8%, HIV 27.5% and glomerulonephritis 9.89% were the four most frequently reported risk factors, of which Black Africans comprised more than 50% of cases (p <0.001). A significant proportion of patients 65.7% (n.307) had end-stage renal disease with a median eGFR of 14.4 ± 12.8ml/min/1.73m2 (p <0.001). The median right and left RL were short at 8.49 ± 2.16cm and 8.60 ± 2.20cm respectively. Black Africans were also found to have significantly shorter RLs and lower eGFRs (p <0.001). The dual effect of IE and LCMD predisposed to significantly shorter RLs and lower eGFRs than in the presence of one or no abnormality on US (p <0.001). IE [-9.29 OR; 95% CI (-13.8 - -4.77); p <0.001] and RL [right: 5.02 OR; 95% CI (3.44 – 6.60); p 0.04; left: 5.11 OR; 95% CI (3.56 – 6.66); p 0.04] were found to be significant predictors of eGFR. HIV was the only risk factor found to be negatively associated with all determined measures of renal function, as well as the sole predictor of IE [2.31 OR; 95% CI (0.17 - 3.15); p 0.02]. Conclusion The CKD epidemic is driven by the complex interplay between communicable (HIV) and NCDs (HPT/DM) and has emerged as an important public health and economic threat in Southern Africa. Africans are most vulnerable presenting with an advanced and accelerated disease course. GFR determination and US are inexpensive means of determining renal function particularly in resource limited settings. IE and RL are surrogate markers of renal function with an increased echogenic pattern being most predictive of renal dysfunction in CKD, particularly in HIV.
The clinical manifestations and response to treatment in South Africans with Lupus nephritis.
(2016) Mody, Priyesh G.; Assounga, Alain Guy Honore.
Systemic lupus erythematosus (SLE) is an uncommon disease which is being recognised with increasing frequency in Africa, including South Africa. It is most common in young women and is associated with a significant morbidity and mortality due to involvement of many organ systems. Lupus nephritis (LN) occurs in about 40 - 60% of patients with SLE and is one of the most common causes of morbidity and mortality in SLE. Reviews of LN in Africa have reported on the spectrum of histological involvement in SLE but there is limited information on the degree of renal impairment at presentation and the response to treatment and outcome. Over the past decade mycophenolate mofetil (MMF) has been widely used as an effective and safer treatment option compared to cyclophosphamide in the management of LN. However, MMF has only been used in 0.4 -15.6% of patients with LN in Africa. This study was undertaken as an audit of our clinical practice to determine the histological classification and renal function at presentation in patients with LN seen at Inkosi Albert Luthuli Central Hospital (IALCH). We also undertook an assessment of the response to induction and maintenance therapy for LN and outcome of treatment during routine care in a tertiary referral centre. We wished to assess whether the presentation and response to treatment in Durban, South Africa is similar to the experience in other parts of the world. The multi-ethnic cohort of predominantly African blacks and Indians seen at our hospital, provided an opportunity to undertake an inter-ethnic comparison of the spectrum of histological classification, stage of chronic kidney disease at presentation, response to treatment and outcome. We conducted a retrospective descriptive study by reviewing the hospital records of patients with SLE who were seen in the Departments of Nephrology and Rheumatology at Inkosi Albert Luthuli Central Hospital from 2003 to 2012. All the patients who had renal involvement and in whom the results of a baseline renal biopsy and baseline laboratory tests were available, were included in the study. The demographic data, results of the renal biopsy and baseline haematological, biochemical and immunological tests were recorded. The records of patients who had Class III and Class IV LN, with or without Class V changes, and patients with Class V LN alone, were analysed further to assess the response to 6 months’ induction therapy and 12 months’ maintenance therapy. The treatment for LN and results of the follow up laboratory results were recorded. The age at diagnosis of LN, gender, results of biochemical and immunological tests, histological classification, treatment and outcome were analysed for all the patients in the study, and separately for African Blacks and Indians as they comprised the majority of the patients in the study. A separate analysis was performed for only those patients who required induction and maintenance therapy for LN (excluding patients with Class I, Class II and Class VI LN). We conducted an analysis of the demographic data, spectrum of histological classification, laboratory findings, stage of chronic kidney disease, treatment and outcome for all the treated patients and also compared the findings between African Blacks and Indians. A comparison of the patients with proliferative LN with membranous LN was undertaken to identify any differences in the demographic data, biochemical or immunological parameters, response to treatment and outcome. The response to treatment was determined for 6 months of induction therapy and after maintenance therapy for 12 months. Patients who achieved a partial or complete remission were classified as responders and patients who did not respond to treatment, were lost to follow up or died, were classified as non-responders. A further analysis of the responders and non-responders was undertaken to identify predictors of a poor response. We identified 105 patients with LN who comprised 52 (49.5%) Indians, 47 (44.8%) African Blacks, 4 (3.8%) Whites and 2 (1.9%) Mixed ethnicity. We found that Class V LN was more common (34.3%) than generally reported in most other studies. There was a higher prevalence of the milder Class II histology in our Indians while severe impairment of renal function (chronic kidney disease stage 5) was more common in African Blacks. There were 87 patients who required treatment for their LN. We found that 81.6% of our patients showed a response to induction therapy and 73.6% showed a response to maintenance therapy. Eight of our patients were lost to follow up prior to their final analysis and they were classified as non-responders, thus contributing to lowering our response rate. International literature has shown a better response to MMF in African Americans compared to Caucasians. We have been able to confirm the efficacy of MMF as induction and maintenance therapy for the first time in our Indians and African Blacks. Our study emphasizes the need to raise awareness of SLE among health professionals so that earlier diagnosis of LN can be made and patients can be treated before there is impaired renal function. We found that nearly 15% of our patients had stage 4 or stage 5 chronic kidney disease (eGFR <30 ml/min) at presentation, indicating significant impairment of renal function. We also found that there was a significant reduction in the response to treatment in patients who had a creatinine ≥132 μmol/l at presentation. This study contributes to the literature on lupus nephritis in Africa and we have shown that MMF is effective in our patients with LN. Thus it provides an alternative safer treatment option than the use of IV CYC.
Clinical profile and outcome of autosomal dominant polycystic kidney disease at a tertiary hospital KwaZulu-Natal, South Africa: a retrospective 5-year review.
(2022) Abulghasm, Taha Mohamed.; Assounga, Alain Guy Honore.; De Vasconcellos, Kim.
No abstract available.
The effect of angiotensin converting enzyme inhibition on nephropathy associated with human immunodeficiency virus infection.
(2005) Han, Thin Maung.; Naicker, Saraladevi.; Assounga, Alain Guy Honore.
Abstract available in PDF.
Outcomes of Myocardial Perfusion Imaging (MPI) using Single Photon Emission Computer Tomography (SPECT) in Diabetic Chronic Kidney Failure (CKF) patients.
(2023) Hassim-Sakoor, Ahmed.; Assounga, Alain Guy Honore.
Abstract available in a PDF.
A retrospective study to determine the prevalence and degree of hyperkalaemia in adult patients with chronic kidney disease, attending the renal clinic at Inkosi Albert Luthuli Central Hospital.
(2022) Bux, Tasneem.; Assounga, Alain Guy Honore.
Chapter 1: Abstract Background: The presence of hyperkalaemia is a known risk factor for the development of cardiac rhythm disturbances and sudden cardiac death. The presence of chronic kidney disease (CKD) is also an independent risk factor for cardiovascular complications. The prevalence of hyperkalaemia in patients with CKD has previously varied widely between studies. The prevalence of hyperkalaemia in the patients attending the renal clinic at Inkosi Albert Luthuli Central Hospital (IALCH) has not been previously determined. Objectives: This study aimed to discover the prevalence of hyperkalaemia in patients attending the renal clinic at IALCH, as well as the degree of severity amongst the patients in whom hyperkalaemia was present. Demographic and other variables were also assessed for an association with hyperkalaemia. Methods: A retrospective review of outpatients attending the renal clinic at IALCH from 1 October 2016 until 30 September 2017. Results: The study consisted of 200 patients, of whom the majority were female (n=120, 60%). The prevalence of hyperkalaemia amongst these patients was found to be 16%. In those with stage 3 CKD, the prevalence of hyperkalaemia was 7.69%. In those with stage 4 CKD, the prevalence of hyperkalaemia was 20.5% and in those with stage 5 CKD the prevalence was 17.3%. There were no statistically significant associations between hyperkalaemia and demographic variables, nor with dietician intervention. There was a significant association with the use of sodium polystyrene sulfonate. Conclusion: CKD is a growing burden in the developing world. With CKD comes metabolic and other derangements, including electrolyte abnormalities as well as increased cardiovascular risk. Hyperkalaemia is associated with worsening CKD. In addition, hyperkalaemia puts patients at risk of cardiac dysrhythmias and sudden cardiac death. Pharmacological measures to manage CVD risk should be weighed up against the risk of hyperkalaemia related complications. Potassium lowering agents should be considered in order to allow for optimal CVD management in the setting of hyperkalaemia in CKD.

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