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This collection contains data collected in the course of clinical work in Nephrology across several hospitals In particular , the CMJAH Living Donor Clinic has a long history . You can see that the work of the unit has inspired or directly produced many thesis. We also have a selection of work on transplants. This collection also includes data on kidney disease from other tertiary hospitals in gauteng



Good day, The Division of Nephrology at Charlotte Maxeke Johannesburg Academic Hospital ( Previously JHB GEN)conducted a research study in the unit’s Living Donor Clinic. The study assessed clinical data of all individuals who presented to this clinic from January 1983 to July 2015. Written permission to access clinical records was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand, Johannesburg. The purpose of the study was to analyze living kidney donation in the South African setting with the hope that the clinical findings of this research may contribute toward the future betterment of care for all potential kidney donors and that this data may expand upon the limited information available in this important field of study. As a patient belonging to this Living Donor Transplant Community, you have the right to direct how your information is shared for use by research platforms. You may engage with the principal investigator of this study should you have any queries regarding how the data from this study is being applied. You may also withdraw consent to share any information you feel is potentially identifying at any point. Should you require any further information regarding the study, please feel free to contact the principal investigator, Dr Chandni Dayal via email

or telephonically on 011 489 0467. Please note that prior to accessing your clinical records, approval was obtained from the Human Research Ethics Committee (Medical) of the University of the Witwatersrand, Johannesburg. A principal function of this Committee is to safeguard the rights and dignity of all individuals who are a part of research projects and the integrity of the research. If you have any complaints or concerns over the way the study was conducted, please contact the Chairperson of this Committee who is Dr. Clement Penny, on telephone number 011 717 2301, or by e-mail

The telephone numbers for the Committee secretariat are 011 717 2700/1234 and the e-mail addresses are and Thank you for reading this notice. 11 March 2022 Dr Chandni Dayal


Recent Submissions

Now showing 1 - 20 of 39
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    Dataset From: Forgotten but not gone in rural South Africa: Urinary schistosomiasis and implications for chronic kidney disease screening in endemic countries
    (2022-12-11) Craik,Alison; Mayindi,Nokthula; Chipungu,Shingirai; Khoza,Bongekile; Gómez-Olivé, Xavier F; Tomlinson, Laurie Alexandra
    Study information The African Research on Kidney Disease (ARK) Study aimed to determine chronic kidney disease (CKD) prevalence and identify associated risk factors in rural South Africa. The study took place from November 2017 to September 2018 and included a population-based sample (N=2759) of adults aged 20-79 years from the Agincourt Health and Socio-Demographic Surveillance System (HDSS) site in rural Bushbuckridge, Mpumalanga Province. Institutional review board approval was obtained from the University of Witwatersrand (clearance number M170583) Written informed consent was obtained from individual participants prior to enrolment. This is a secondary data analysis nested within the ARK study. In this population-based cohort study, we aimed to characterise the burden of urinary schistosomiasis in rural South Africa and evaluate its relationship with markers of kidney dysfunction with implications for CKD screening. We recruited 2021 adults aged 20-79 years in the Mpumalanga Province, South Africa. Sociodemographic and anthropometric data were recorded, urinalysis performed, and serum and urine samples collected. We measured serum creatinine and urine albumin/creatinine. Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2 and/or urine albumin-creatinine ratio >3.0mg/mmol. S.haematobium infection was determined by urine microscopy. Multivariable analyses were performed to determine relationships between S.haematobium and kidney dysfunction. The methodology for this sub-study is dependent on the larger ARK study processes. Data quality and ethics processes have previously been validated by the ARK consortium . Institutional review board approval was obtained from the University of Witwatersrand (clearance number M170583) Written informed consent was obtained from individual participants prior to enrolment. Additional approval for this sub-study from the London School of Hygiene and Tropical Medicine (reference number 22152). Kalyesubula R, Fabian J, Nakanga W, Newton R, Ssebunnya B, Prynn J, et al. How to estimate glomerular filtration rate in sub-Saharan Africa: design and methods of the African Research into Kidney Diseases (ARK) study. BMC Nephrol. 2020 Jan 15;21(1):20.
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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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    WDGMC Paediatric Liver Transplant Research Database
    (REDcap, 2019-12-09) Fabian, June; Botha, Jean; Van der Schyff, Francisca.; Terblanche, Alberta J
    Biliary atresia (BA) is a progressive fibrosing cholangiopathy of infancy, the most common cause of cholestatic jaundice in infants and the top indication for liver transplantation in children. Kasai portoenterostomy (KPE) when successful may delay the requirement for liver transplantation, which in the majority offers the only cure. Good outcomes demand early surgical intervention, appropriate management of liver cirrhosis, and in most cases, liver transplantation. These parameters were audited of children with BA treated at the Steve Biko Academic Hospital (SBAH) in Pretoria, South Africa.
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    Dataset from: Chronic kidney disease (CKD) and associated risk in rural South Africa: a population-based cohort study
    (2022-07-13) Fabian, June; Gondwe, Mwawi; Mayindi, Nokthula; Khoza, Bongekile; Gaylard, Petra; Wade, Alisha N.; Gómez‑Olivé, F. Xavier; Tomlinson, Laurie A.; Ramsay, Michele; Tollman, Stephen Meir; Winkler, Cheryl; George, Jaya Anna; Naicker, Saraladevi; Study data were collected and managed using opensource REDCap electronic data capture tools hosted at the University of the Witwatersrand
    Study Methods This longitudinal cohort study was conducted from November 2017 to September 2018 in the Medical Research Council (MRC)/Wits Rural Public Health and Health Transitions Research Unit (otherwise referred to as "Agincourt") in Bushbuckridge, a rural subdistrict of the Mpumalanga province in north-eastern South Africa. Agincourt is a Health and Socio-Demographic Surveillance System (HDSS) site that includes approximately 115,000 people. For this study, a minimum sample size of 1800 was required to provide at least 80% power to determine CKD prevalence of at least 5%, provided the true prevalence was equal to or more than 6.5%. Proportional allocation of Black African adults aged 20 to 79 years ensured a representative sample based on the most recent annual population census. Sample size was increased proportionately to 2759 individuals to accommodate a 25% non-participation rate. Dataset is 2022 cases Variables are: 1. age 2. Gender 3. Years of Education (refers to completed years of schooling) 4. Height (cm) (one decimal place) 5. weight (kg) (one decimal place) 6. BMI (body mass index) 7. POC random cholesterol (mmol/L) (2 decimal places) 8. POC random glucose (mmol/L) (1 decimal place) 9. HIV status is: Based on (i) prior HIV testing history OR (ii) HIV PCR testing for ARK 10. Using the urine pregnancy test, is this participant pregnant? ( 11. ERY (erythrocytes, blood) 12. Hb (haemoglobin, blood) LEU (leucocytes) 13. NIT (nitrites) 14. PRO (protein) 15. hepatitis B surface antigen 16. Serum creatinine (umol/L) 17. Systolic BP(1) 18. Diastolic BP (1) 19. Systolic BP(2) 20. Diastolic BP (2) 21. Systolic BP(3) 22. Diastolic BP (3) 23. Serum creatinine (umol/L) 24. Urine microalbumin (mg/L) 25. Urine creatinine (mmol/L) 26. Urine microalbumin (mg/L) 27. Urine creatinine (mmol/L) 28. APOL1 haplotype
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    Dataset from: Clinicopathological correlation of kidney disease in HIV infection pre- and post- ART rollout: VERSION 2
    (2022-04-14) Diana, Nina Elisabeth; Davies, Malcolm; Mosiane, Pulane; Vermeulen, Alda; Naicker, Saraladevi
    Data note Methods Ethics approval for this study was granted in writing by the Human Research Ethics Committee (Medical) of the University of the Witwatersrand, Johannesburg, South Africa (clearance certificate numbers M1511104, M121184, M120874). This approval permitted a record review of all HIV-positive patients who underwent a kidney biopsy at two tertiary hospitals in Johannesburg within the defined study period. Informed consent for this retrospective record review was waived. Data from included patients was anonymised prior to statistical analysis. Renal biopsies performed at these two tertiary hospitals, on HIV-positive individuals, from January 1989 to December 2014 were retrospectively analysed. Demographic data (age, sex and race), clinical parameters (CD4 count, HIV viral load, serum creatinine and urine protein creatinine ratio), indication for biopsy and renal histological pattern was recorded at time of kidney biopsy. The estimated glomerular filtration rate (eGFR) was calculated according to the CKD-EPI creatinine equation without ethnicity correction. ART rollout began in April 2004 in South Africa. Patients were divided into 2 groups - those who were biopsied pre-ART rollout and those biopsied post-ART rollout. These two groups were compared with respect to the above parameters. In a subgroup of the patients biopsied between 2004 and 2014, additional data laboratory parameters (serum haemoglobin, serum albumin, serial serum creatinine and eGFR) and ART use (at time of biopsy) were recorded. All renal biopsies were processed according to standard techniques for light microscopy, immunofluorescence and electron microscopy. All biopsies were reviewed by the National Health Laboratory Service histopathology team who were aware of the HIV status of the patient at time of biopsy. Histological diagnoses were tabulated using the 2018 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference guidelines. As per this guideline FSGS (NOS) in the setting of HIV describes all non-collapsing forms of FSGS. Those ICGN with no identifiable comparative etiology other than HIV were categorized as uncharacterized ICGN with no etiology other than HIV. The biopsies with multiple diagnoses were assigned its major clinical-pathological diagnosis for the purposes of analysis. All data was collected by Dr Nina Diana and Dr Alda Vermeulen from paper based patient hospital records and the electronic hospital laboratory system. All data was checked twice to ensure accuracy. Each patient was allocated a study number and data anonymised prior to entry into Microsoft Excel. Shapiro Wilk W testing and visual inspection of the histogram plot indicated non-parametric distribution of baseline characteristics of the cohort; accordingly, central and dispersal measurements were described using the median and interquartile range (IQR), and the Kruskal Wallis ANOVA and Mann-Whitney U tests were used for comparative analyses. Kidney survival, defined by an eGFR above threshold for consideration for dialysis initiation in these institutions (15mL/min/1.73m²), censored for patient default with preserved function, was fitted for patients in the subgroup using the Kaplan Meyer method; histological diagnoses were compared using Log-rank testing.
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    Dataset From: Evaluation of potential kidney donors and outcomes post-donation at Charlotte Maxeke Johannesburg Academic Hospital (1983-2015)
    (Division of Nephrology, Charlotte Maxeke Johannesburg Academic Hospital, 2022-03-23) Dayal, Chandni; Davies, Malcolm; Diana, Nina Elisabeth; Meyers, Anthony M.
    Data was collected from existing clinical records of the Living Donor Clinic held by the Division of Nephrology at Charlotte Maxeke Johannesburg Academic Hospital. This was performed by the primary investigator / first author in a pseudo-anonymized fashion and stored securely in an Excel database to which only the primary investigator had access along with the data key. Procedures pertaining to original data capturing to clinical records by the data manager (Sister Nancy Makoe), were in accordance with the standard operating procedure set out by the Transplant Unit at Charlotte Maxeke Johannesburg Academic Hospital. Objectives of research Primary Objective • To determine donor morbidity and mortality after donation. • Analysis of morbidity will focus on the development of - New onset hypertension following donation (BP ≥140/90) - Chronic kidney disease following donation, defined as the development of either of the following - New onset proteinuria (AER >300mg/day) - An eGFR <60 ml/min/1.73 m² (using the CKD-EPI formula) Secondary Objectives • To determine the reasons for exclusion of potential donors from living kidney donation • To determine the prevalence of ESKD following donation (eGFR <15 ml/min/1.73 m² using the CKD-EPI formula) • To determine potential risk factors associated with proteinuria and/or a reduced eGFR post kidney donation, by evaluating a. donor demographics b. the presence of isolated medical abnormalities prior to donation, defined by: - a borderline pre-donation 51Cr-EDTA GFR (<80 ml/min/1.73 m²) - pre-existing hypertension (well controlled on a single agent with no end-organ damage) - class I obesity (BMI 30-35 kg/m²) • To determine the proportion of patients lost to follow-up post donation 5.2 Study design A single centre retrospective observational study was conducted of all patients attending the Living Donor Clinic in the Renal Unit at CMJAH over a 32-year period between 01 January 1983 and 31 July 2015. The closing date for sampling reflects the period of protocol submission for this study. The cohort comprised of 1208 potential living donors, of which: • 910 are failed living donors, assessed between 01 January 1990 and 31 July 2015 • 298 are accepted living donors, assessed between 01 January 1983 and 31 July 2015 5.3 Data collection 5.2.1 Data collection for failed living donors Data collection for failed living donors comprised the following parameters: • Demographic data – age at assessment, gender and ethnicity • Family history of the donor • Relation to the intended recipient – whether related, unrelated or altruistic • The outcome of eligibility evaluation • If excluded from living donation, reasons for non-donation will be documented, which were categorised as: - donor-recipient related, - donor-related, - recipient-related, or - miscellaneous. • The indications and findings of any renal biopsy undertaken on a donor was recorded 5.2.2 Data collection for accepted living donors Data collection for accepted living donors comprised the following parameters: • Demographic information – gender, ethnicity, age at donation (as well as age at each follow-up point) • Family history of the accepted donor • Details pertaining to the donation, specifically: - relation to the recipient, as well as cause of renal failure in the recipient - the date of donation - the graft outcome (if known) • The last follow-up date at the Living Donor Clinic and the approximate number of post-donation follow-up visits • Domicile in relation to the Living Donor Clinic (in kilometres from transplant centre) • The reason for lost to follow-up (if known) • Baseline characteristics at donation, including: - Body mass index - Urine albumin: creatinine ratio - Systolic blood pressure - Diastolic blood pressure - Baseline serum creatinine - eGFR as defined by an isotope study, the chromium-51-ethylene-diamine-tetra-aceticacid scan (51Cr EDTA scan) as well as the CKD-EPI formula - Habits, including smoking status and history of alcohol consumption - History of pre-existing medical condition(s) • Characteristics at follow-up (correlated with time after donation), including: - Body mass index - Urine albumin: creatinine ratio - Systolic blood pressure - Diastolic blood pressure - Serum creatinine - eGFR as defined by the CKD-EPI formula - Habits, including smoking status and alcohol consumption - Development of co-morbid disease - History of nephrotoxic drug intake The above variables were retrospectively collected from data recorded at the patients’ first follow-up visit post-donation, one-year post-donation visit, and at the most recent follow-up visit. • Mortality data was collected in accepted living donors that demised during the study period, and will include: - age at death - the time from donation to mortality - cause of death, whether related to renal disease, a cardiovascular event or other cause 5.3 Definition of variables 5.3.1 Classification of donors • Potential living donors (PLDs) – refer to all donors assessed at the CMJAH Living Donor Clinic • Failed living donors (FLDs) – refer to the sub-group of PLDs excluded from living kidney donation • Accepted living donors (ALDs) – refer to the subgroup of PLDs that ultimately donated a kidney 5.3.2 Hypertension Defined as per the Eighth Joint National Committee (JNC8) guidelines for blood pressure targets: • For donors with a current age of more than sixty years: - a systolic blood pressure of more than 150mmHg, with - a diastolic blood pressure of more than 90mmHg • For donors with a current age of less than sixty years: - a systolic blood pressure of more than 140mmHg, with - a diastolic blood pressure of more than 90mmHg 5.3.2 Albuminuria Quantified as per the revised Kidney Disease Improving Global Outcomes (KDIGO) chronic kidney disease classification into three stages of albuminuria based on the albumin excretion rate (AER) in milligrams per day (mg/day): • A1: Normal or mildly increased (AER <30 mg/day) • A2: Moderately increased (AER between 30 - 300 mg/day) • A3: Severely increased (AER >300 mg/day, with nephrotic range proteinuria defined as >3500 mg/day) 5.3.3 Glomerular filtration rate • Pre-donation GFR will be defined: - as per isotope study: 51Cr EDTA scan - as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, expressed as: GFR = 141 × min (Scr /κ, 1) α × max (Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] where: GFR = glomerular filtration rate in ml/min/1,73m2 Scr = serum creatinine in mg/dL κ = 0.7 for females and 0.9 for males α = -0.329 for females and -0.411 for males min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1. • Post-donation GFR will be calculated by the CKD-EPI formula, as expressed above. 5.3.4 Chronic kidney disease Defined as per the revised Kidney Disease Outcomes Quality Initiative (KDOQI) as either kidney damage or GFR<60 ml/min/1.73 m² for ≥ 3 months. Kidney damage encompasses pathological abnormalities or markers of damage, including biochemical or radiological abnormalities. GFR is further classified into stages (table 1.1). Table 1.1 | Revised KDOQI classification for chronic kidney disease GFR Stages GFR (ml/min/1.73 m2) Classification 1 >90 Normal 2 60 – 89 Mildly decreased 3a 45 – 59 Mildly to moderately decreased 3b 30 – 44 Moderately to severely decreased 4 15 – 29 Severely decreased 5 <15 ESKD 5.3.5 Body mass index • BMI will be calculated as weight (in kilograms) divided by height (in meters) squared. • It will then be sub-classified as per the World Health Organisation (WHO) international BMI classification (table 1.2). Table 1.2 | WHO international classification of BMI Classification BMI (kg/m2) Underweight < 18.5 Normal Range 18.5 to 24.99 Overweight Pre-obese Obese - Obese Class I - Obese Class II - Obese Class III ≥ 25 25 to 29.99 ≥ 30 30 to 34.99 35 to 39.99 ≥ 40 5.3.6 Isolated medical abnormalities Refers to donors with any of the following characteristics prior to donation: • A borderline 51Cr-EDTA GFR <80 ml/min/1.73 m2 • Pre-existing hypertension well-controlled on a single agent with no end- organ damage • Class I obesity (BMI 30 - 35 kg/m2 )
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    An argument for a paid and regulated living-unrelated kidney donation system in South Africa
    (2021) Ewing (Naude), Susan Lesley
    One of the biggest challenges that global healthcare is experiencing is the shortage of kidney organ donors. Globally, the demand for organs is far greater than the supply and as a result, people who are on waiting lists will not get a chance to receive a kidney. Those who are waiting for transplants will require ongoing dialysis to survive (Nath & Fervenza, 2018). Dialysis is extremely costly and burdens the healthcare systems. Given the enormous gaps between supply and demand, this report seeks to answer the question: “Should South Africa follow the model of a paid and regulated living unrelated kidney donation system?” I begin with an analysis of South Africa’s current structure, the effects of this system and ultimately seeing the need for a different solution. I analyzed the various models globally in kidney donation, including the only country that allows for a paid system and the objections thereto. Currently, the sale of organs is prohibited in South Africa. My view is that our current South African model is lacking in solutions to the shortage of organ donors, particularly kidneys. There is a need for a better solution as the current system is failing to meet the needs of patients. In this paper, I use the principlism framework consisting of the four bioethical principles namely, autonomy, beneficence, non-maleficence and justice, to highlight the constitutional conflicts and the ethical dilemmas when considering a paid donation system. As I am arguing for a paid system in South Africa, I have included the ubuntu theory to show why objections to a paid and regulated system would fail. In conclusion, a paid and regulated living-unrelated kidney donation system is argued to be the most ethically and practically appropriate system in South Africa, to improve kidney donation rates and the livelihoods of the people
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    Outcomes of paediatric liver transplant for biliary Atresia
    (2021) Gamiet, Yentl Leigh
    Background: Despite the widespread use of Kasai Portoenterostomy (KPE) for biliary atresia, more than two thirds of these patients require liver transplant. Liver transplantation is not widely available in South Africa, and Wits Donald Gordon Medical Centre is one of two centres performing paediatric liver transplantation in the country, and the only centre performing living related donor transplants. The study aims to outline the experience with liver transplant for biliary atresia in terms of the post-operative complications and one-year survival outcomes, with the goal to ascertain the factors which govern those outcomes. Methods: A retrospective review was performed at the centre. Demographic data was collected, and tabulated. Survival analysis was performed using Kaplan Meier curves. Complication rates were categorised into biliary, vascular and enteric complications, and classified as early and late. Mortality was analysed according to cause and timing which was categorised as early and late. Results: Sixty-seven first time liver transplants were performed for biliary atresia, at WDGMC from 2005 to 2017. Sixty-nine percent were female patients and thirty-one percent were male patients. Forty-eight percent of patients under the age of 5 years, had a z-score of -2 or worse for mid upper arm circumference (MUAC). The rates of biliary complications, enteric complications and vascular complications were 34%, 12% and 12%, respectively. One-year overall survival of the cohort is 84.5%, and overall graft survival is 82.9%. Overall mortality was 22% but cause of death was difficult to corroborate. Conclusion: Complication rates and survival outcomes are comparable to international single centre studies despite the high rates of malnutrition in our study cohort. Early referral of all patients with biliary atresia to a paediatric liver transplant centre is essential for early detection of indications, and medical and nutritional optimisation of patients
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    Kidney transplant related knowledge and health education needs of patients with chronic kidney failure in two academic hospitals in Gauteng
    (2021) Nkadimeng, Mmabje Calvin
    Background: Patients living with chronic kidney failure endure a lot of stress, as they have to adjust their lifestyle, stop smoking, eat a healthy diet, and refrain from self-medication. Currently, South Africa has dearth in literature regarding the knowledge of these patients about kidney transplant, which is so far the best treatment for chronic kidney failure. Patients are provided with health education before any transplant, this is done to equip them with adequate knowledge regarding the disease and its management. However, there are no methods to examine whether the patient comprehended the information or not. Purpose: The purpose of this study was to describe the kidney transplant related knowledge and health education needs of patients with Chronic Kidney Failure on haemodialysis awaiting kidney transplant in two hospitals in Gauteng. Methods: The study was a quantitative, descriptive and cross-sectional survey and data was collected using a kidney transplant understanding tool (K-TUT) questionnaire. Data analysis: Data was analysed using the statistical package for Social Science computer Programme and quantitative content analysis. Setting: The setting for this study was the renal units at two academic hospitals in Gauteng, South Africa. Results: Of the n=124 aimed sample size, n=70 patients gave consent to participate in the study, based on the set objective of describing the knowledge of patients on dialysis about their knowledge on kidney transplant, a large number n=58 (82.86%) scored above 50% indicating adequate knowledge and n=12 (17.14%) scored below 50%, which is regarded as inadequate knowledge. However, at the mean score of 55%, only half (n=35; 50%) of the participants had adequate knowledge. When considering the 55% as adequate knowledge indicator, half of the participants had inadequate knowledge regarding kidney transplant. The health education needs revealed three themes: firstly, the health education needs related to kidney transplant (quality of life, reproductive health and risks and side effects). Secondly the additional information needs to understand kidney transplant process such as donors and support system and lastly the family member involvement theme which entailed their family member understanding of the risk of rejection and infection
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    Audit of acute rejection in renal allografts
    (2020) Thomas, Riju Mathew
    Acute graft rejection is acknowledged to have a negative impact on graft survival in renal transplantation. South Africa provides for limited renal transplantation amidst the increasing burden of chronic kidney disease in the local context. Despite this suboptimal provision and limited resources, amongst many other concerns, the role of acute graft rejection on graft survival has not been characterized in the context of South Africa, as well as the African continent. This study is an audit, characterising acute graft rejection diagnosed at the Charlotte Maxeke Johannesburg Academic Hospital over a ten-year period (2003-2012). The study revealed the incidence of acute rejection in renal transplants to be 34.5%, similar to that reported in international studies. The majority of acute rejections occurred within the first year of transplantation (53.8%), which was lower than that reported in other studies, with 40% of patients having recurrence of acute rejection. The main form of rejection diagnosed was acute cellular rejection (predominantly BANFF grades 1A and 1B), followed by Borderline acute cellular rejection, the combination of which comprised the majority (86.9%) of all rejections diagnosed. This population was found to be a male dominant and Black African dominant study group, in keeping with the racial distribution of the dialysis population of South Africa, commonly influenced by treatment-seeking behaviour. Cadaveric donor grafts were engrafted in 77.7% of this population and 77.8% of the population had less than 40% of HLA antigens in common with their donor. Delayed graft function was observed in 22.4% of recipients with a significant association with more severe acute graft rejection. Hypertension was the most dominant primary aetiology leading to chronic kidney disease of native kidneys in this population. Immunosuppressive regimen, including cyclosporin, mycophenolate mofetil and prednisone, was used in 80% of recipients, with 97.6% of recipients on mycophenolate mofetil and prednisone. The five-year survival of grafts developing acute rejection was 61.7%. Graft function deteriorated more dramatically amongst recipients who progressed to graft loss, with recovery of graft function observed to be more prominent amongst recipients with surviving grafts. This study adds to the literature on this topic, and also describes the characteristics and outcomes of this entity.
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    Factors influencing CD4+ T cell counts in people living with HIV with end-stage kidney disease
    (2020) Pretorius, Melanie
    Introduction: In South Africa, it is estimated that ~7 million people are living with Human Immunodeficiency Virus (HIV). HIV is associated with an increased risk of kidney disease. For people living with HIV (PLWH) who develop end-stage kidney disease (ESKD), access to renal replacement therapy can be difficult. Kidney transplantation is a cost-effective option, with improved overall survival and better quality of life. Eligibility criteria for kidney transplantation in Johannesburg includes a sustained CD4+ T cell count of >200 cells/μl and suppressed HIV replication. This study aimed to investigate the influence of hemodialysis on the lymphocyte subsets in PLWH with ESKD. Methods: Study participants and controls were recruited from renal dialysis centres in Johannesburg. Demographic data, social data, serial CD4+ T cell counts, serial HIV viral load measurements and blood samples were collected (before and after a haemodialysis session). Lymphocyte subsets were then measured. Results: Our cohort showed a statistically significant increase in the post-dialysis % of CD4+ T cells and the absolute CD4+ T cell counts. The longitudinal trend analysis for the % of CD4+ T cells revealed a significant increase in five participants and a single patient had a significant decrease in the longitudinal trend analysis for the absolute CD4+ T cell counts. The longitudinal trend analysis for HIV viral load revealed the majority of our participants were not virologically suppressed. Conclusion: This study showed that haemodialysis does not negatively impact CD4+ T cell count, suggesting that immunologic recovery is not impeded by treatment of the underlying ESKD.
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    Graft survival in South African renal transplant patients during the transition period at Charlotte Maxeke Johannesburg Academic Hospital (graft-sat study)
    (2020) Chhiba, Priya Darshani
    Introduction: In the developed world, studies performed on the transition of adolescent renal transplant patients have noted high rates of rejection, non-adherence and graft loss. However, there is paucity of data in developing countries, and none in a South African setting. Objectives: The purpose of this study was to assess the rates of acute and chronic rejection, graft and patient survival in adolescents at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methods:This study was a retrospective analysis of patients who received a renal transplant from 1 January 1990 to 31 December 2010, in the Paediatric Nephrology Department at CMJAH, in Parktown, Johannesburg, and entered the adolescent period (10 to 19 years old) with a functioning graft. Patients were included whether or not they were transferred to the Adult Nephrology Department at CMJAH.Results: 162 recipients were patients were transplanted during the study period, of which 80 (49.4%) were of black race, 63 (38.9%) were white, 10 (6.2%) were Asian and 9 (5.5%) were of mixed race. 65 (40.1%) were female and 97 (59.9%) were male. The median age at transplant was 13.8 years old (Interquartile range (IQR): 10.6 to 15.9). One hundred, twenty-eight (79.0%) patients received a renal transplant during the adolescent period and 34 (21.0%) were transplanted prior to adolescence. Fifty-four (33.3%) patients were transferred to the adult unit during adolescence. Graft failure occurred in 60 (37.0%) of the patients during the adolescent period, of which 54 (90.0%) occurred in the paediatric unit and 6 (10.0%) occurred in the adult unit. The median age at graft failure in the adolescent period was 16.1 years old (IQR: 14.5 to 17.9). Kaplan-Meier curves were used to analyse graft and patient survival. The following factors were identified as statistically significant in contributing to graft failure: if the transplant occurred during adolescence, previous renal transplant,non-compliance and rejection episodes in the adult unit, (p value <0.05). The 1, 3, 5, and 10-year patient survival rates were 98.8%, 97.6%, 95.1% and 93.9% respectively. Conclusion: This study revealed high rates of graft rejection and loss in South African renal transplant recipients in the adolescent period highlighting the vulnerability of this population group. Consideration should be given to the creation of transition clinics to potentially improve the graft outcomes of this vulnerable group. Further studies are needed on the transition period of adolescent renal transplant patients.
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    The influence of dialysis modality on post-transplant outcomes
    (2020) Boosi, Reece
    Introduction: Renal transplantation is the therapy of choice for end stage kidney disease, offering mortality risk reduction and improved morbidity over dialytic therapies. Limited data is available evaluating the effect of pre-engraftment dialysis modality on transplant outcomes. Methods: A retrospective review was conducted of all adult patients undergoing renal transplantation at Charlotte Maxeke Johannesburg Academic Hospital for the period 01/01/2006 – 31/12/2011 (n=103). Transplant outcomes were assessed by dialysis modality. c2 testing was used to compare dialysis modalities; Cox proportional hazard modelling was used to assess effect on graft outcomes. A p < 0.05 was deemed statistically significant. Results: Antecedent dialytic modality was as follows: 55 patients (53.4%) received haemodialysis (HD), 35 (34%) received peritoneal dialysis (PD), and 13 (12.6%) received a combination of both (HD+PD, defined as either modality for > 3 months). Acute rejection (AR) was documented in 43.7% of patients; 54.3% of PD patients developed AR compared to 38.2% of HD patients and 38.5% of HD+PD patients (p=0.29). No significant difference in the number of episodes of AR was detected between modality groups (p=0.44). Chronic rejection (CR) developed in 22.3% of patients overall; 21.8% of HD patients, 25.8% of PD and 15.9% of HD+PD patients (p=0.74). PD was associated with an increased risk of developing any rejection (HR=2.4, 95% CI 0.9–6.4, p=0.02). Whereas dialysis modality did not affect graft survival (for HD b= 0.57, SE=0.5, Wald=1.2, 95% CI -0.4-1.6, p=0.27; for PD b=0.58, SE=0.5, Wald = 1.4, 95% CI -0.4-1.6, p=0.24), AR was found to be associated with futuregraft loss (b=1.29, SE=0.3, Wald = 18.1, 95% CI 0.7-1.9, p<0.001).Conclusions: Antecedent PD is associated with an increased risk of graft rejection. Although AR is associated with graft loss, antecedent dialysis modality does not directly predict graft survival, likely reflecting the multifactorial nature of cumulative allograft injury.
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    Challenges faced by Gauteng nephrology nurses regarding implementing evidence based practice
    (2020) Dube, Elizabeth Lerato
    Introduction: Evidence-based practice is an expected core competence of all health care clinicians regardless of discipline. Melnyk and Fineout-Overholt (2014) noted that although there is an explosion of scientific evidence available to guide clinical practice, the implementation of evidence-based care by health professionals is typically not the norm in many healthcare systems across the globe. The researcher undertook this study to gain an understanding of what is preventing the nurses from implementing EBP in the nephrology nursing departments in Gauteng. Purpose of the study was to describe challenges related to EBP implementation that were faced by nephrology nurses in clinical practice and to describe the recommendations that will assist them to successfully implement. Methods. This study followed a qualitative, exploratory, descriptive and contextual approach and was conducted in nephrology units in Gauteng Province. The population of this study included trained nephrology nurses registered with the South African Nursing Council (SANC) and meeting the eligibility criteria. Data was collected from three phases and analysed using Hsieh and Shannon (2005) conventional data analysis method. Results: Sixteen sub categories emerged which were condensed to three categories of Management Practices, Perceived organizational support and leadership practices and Training and Development. Results included studies recommending the middle manager to be the link between nurses at the operational level and top management, who can successfully drive EBP and assist in alleviating experienced challenges. Recommendations were described
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    The use of chronic dialysis in a resource-poor environment: demographic features and transplant readiness at Helen Joseph Hospital renal unit
    (2019) Parbhoo, Dinen
    Background Chronic kidney disease (CKD) places a considerable economic strain on health care systems. In South Africa resource limitations in the public sector mandate that patients with end stage renal disease (ESRD) are only offered dialysis if they qualify for renal transplant. Thus, chronic dialysis serves as a bridge to transplantation. Objectives The primary objective of this study was to describe the patients on the chronic dialysis program with regards to demographic features, aetiology of renal failure, associated chronic comorbidities and transplant readiness. Secondary objectives included the determination of the type and duration of dialysis used and the documentation of any possible differences between the haemodialysis (HD) and peritoneal dialysis (PD) groups and the HIV positive and negative patients. Methods A cross-sectional record review was conducted of all patients receiving chronic dialysis at the Helen Joseph Hospital’s Renal Unit as at September 2016. Information regarding demographic features, disease profile, year of initiation of dialysis, year of presentation, Human Immunodeficiency Virus (HIV) status and transplant readiness was collected. All data was analysed at a 95% confidence interval and a p value of <0.05 was considered significant. Results There were 92 patients on chronic dialysis, 46 each on PD and HD. The mean (SD) age of patients in this study was 43.8 years (10.8). There was a slight female predominance (51.1%). The predominant ethnic group was African (64.1%). The leading causes of ESRD were hypertension (35.9%) followed by diabetes mellitus (10.9%). The most frequent comorbidity was hypertension (98.9%) followed by HIV infection (36.1%). The median time that patients spent on dialysis before presentation for transplant listing was 2 years (range 0-9 years). At the time of analysis, 27 patients (29.4%) were eligible for transplant and 38 patients (41.3%) were in the process of transplant eligibility evaluation. Twenty-seven patients (29.4%) were ineligible for transplant. Of those eligible for transplant, 21 were listed for transplant and 6 were awaiting presentation for listing. There were no differences between the HD and PD groups or the HIV positive and negative groups with regards to qualification for transplant. Conclusion The demographic features and underlying aetiologies of our cohort are similar to national figures with only the racial composition being different. The proportion of patients listed for transplantation (22.8%) and median time for work-up (2 years) are both sub-optimal. Improved efficiency in the evaluation of transplant eligibility is required in order to optimize the appropriate allocation of dialysis in a resource-limited setting.
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    Evaluation of potential kidney donors and outcomes post-donation at Charlotte Maxeke Johannesburg acdemic hospital (1983 - 2015) a
    (2019) Dayal, Chandni
    Background Living kidney donation has emerged as a key therapeutic modality for end-stage kidney disease due to the global chronic shortage of renal allografts. However, the potential benefits to the recipient of a living donor kidney must be balanced against donor safety. In demographically diverse populations, there is a paucity of data regarding the living donor evaluation process and outcomes following donation. Objectives This study was undertaken to describe donation patterns, characterise reasons for nondonation and evaluate long-term morbidity and mortality following living kidney donation in the South African context. Methods A retrospective analysis of all Potential Living Donors (PLDs) evaluated at a single centre over a 32-year period was conducted. Of the total cohort of 1208 PLDs, 298 were Accepted Living Donors (ALDs), resulting in 910 Failed Living Donors (FLDs). Data collected included donor demographics. In addition, in the ALD group, clinical and laboratory parameters at various points in donor follow-up, as well as mortality data was noted. In the FLD group reason for donor exclusion was documented. Results Of the 1208 PLDs, 697 (58%) were female. The majority (559; 46%) were of Black African descent, and related to the intended recipient (991; 82%). Outcome of PLD evaluation varied significantly by race (p<0.001), with only a third of Black PLDs being accepted for donation. Black vs. Caucasian PLDs were more likely to fail workup (52.1% vs. 39.3%; p<0.001) and be excluded for medical reasons (44% vs. 35%; p<0.001). Leading medical exclusions included hypertension, HIV and obesity. In the ALD cohort, median follow-up time was 44 months (IQR 13.8 – 93.5 months). Hypertension was documented in 12.8% of ALDs at most recent follow-up compared to 4.7% of ALDs pre-donation (p=0.06). There was a significant increase in Albumin Excretion Rate (AER) following donation (p<0.001). There was a significant decline in the CKD-EPI eGFR between pre-donation (91.7 ± 19.1 ml /min/1.73 m2) and the most recent visit postdonation (72.5 ± 20 ml/min/1.73 m2; p<0.001). 27% of ALDs had a CKD-EPI eGFR<60 ml/min/1.73 m2 at most recent visit, however none required renal replacement therapy. There were 5 documented deaths, all unrelated to the development of renal dysfunction. Black ethnicity was not associated with increased risk of adverse outcome following donation. Conclusions There is a high exclusion rate for PLDs. Black PLDs are more likely to be excluded than Caucasian counterparts due to significant comorbidity. Although limited by high rates of donors lost to follow-up, it is concerning that a quarter of ALDs developed an eGFR<60 ml/min/1.73 m2 at last follow-up, with a significant increase in AER.
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    Relationship of Chronic Inflammatory Markers and Dyslipidaemia to Atherosclerotic vascular disease in different categories of chronic kidney disease patients
    (2018) Oguntola, Stephen Olawale
    Background: Cardiovascular disease (CVD) is the leading cause of mortality among CKD patients, responsible for 40-50 % of all-cause mortality in CKD. Chronic kidney disease patients have been shown to be more likely to succumb to CVD than progress to ESKD. Atherosclerotic vascular disease (AsVD) has been described as an inflammatory disease because of the central role of chronic inflammation and lipid disorders in its aetiopathogenesis. The contributions of these two risk factors have not been well studied in a broad spectrum of CKD patients among black Africans. This study evaluated the relationship of chronic inflammation, dyslipidaemia and APOL1 risk variants to AsVD among black South Africans with CKD stage 3, peritoneal dialysis (PD) and haemodialysis (HD) patients and kidney transplant recipients (KTRs). Methods This was a cross-sectional study of 40 adult (18-65 years) non-diabetic CKD patients, kidney disease outcome quality initiative (KDOQI stage 3), 40 PD patients, 40 HD patients, 41 KTRs and 41 age- and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants’ sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Blood samples were obtained and serum was analysed for baseline tests, lipoprotein and inflammatory biomarkers. Genomic DNA was extracted from whole blood by modified salting out method and APOL1 genotyping was carried out using restriction fragment length polymorphism. Echocardiography was performed on all patients and carotid intima media thickness (CIMT) was assessed in both right and left carotid arteries at 1cm proximal to the carotid bulb. Atherosclerotic vascular disease was defined by the combination of increased CIMT values (> 0.55 mm) and the presence of carotid plaques. Results: Prevalence of AsVD was highest among PD patients (70 %), and occurred in 47.5 % of stage 3CKD and HD patients, 46.3 % of KTRs and 17.1 % of controls, (p < 0.01). Comparison of the kidney disease groups (CKD stage 3, PD and HD) with controls showed significant difference in waist-hip ratio (WHR), systolic blood pressure (SBP), mean arterial blood pressure (MABP), serum creatinine (Scr), estimated glomerular filtration rate (eGFR), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C-C), Castelli 1, Castelli 2, atherogenic coefficient (AC), non-HDL-C cholesterol, calcium, phosphate, calcium-phosphate products (CaXPO4), serum albumin, ejection fraction (EF), left atrial diameter (LAD) and left ventricular mass index (LVMI). Comparison between the kidney disease group (CKD stage 3, PD and HD) who had AsVD with those who did not, showed significantly higher age, WHR, LAD, mitral valve deceleration time, LVMI and serum creatinine. Among KTRs, positive correlation was seen between CIMT and LAD, LVMI, Castelli 2 and Lipoprotein combined index (LCI). Pentraxin-3 levels were significantly higher in all the kidney disease groups (stage 3 CKD, PD, HD and KTRs) compared to controls. high sensitivity C-reactive protein (hsCRP) and tumour necrosis factor-alpha (TNF-α) levels were significantly higher in ESKD patients compared to controls. Pentraxin-3 correlated positively with CIMT among KTRs (r = 0.336, p = 0.032) and with other inflammatory markers when all kidney disease groups were combined (except for hsCRP). An inverse correlation was seen between pentraxin-3 and eGFR (r = -0.171, p = 0.030) and serum albumin (r = -0.168, p = 0.033). The levels of Lp (a) and Lp-PLA2 were increased while levels of APO A1 were reduced in all kidney disease groups compared to controls. On multivariate analysis, age (> 40 years), male gender, low HDL-C levels and elevated Lp (a) levels independently predicted AsVD after adjusting for BMI, WHR, TC, TG, HDL-C, LDL C, inflammatory markers, Lp-PLA2 and APO A1. Lipoprotein (a) predicted AsVD better than other lipid markers evidenced by higher area under the curve (AUC). No significant difference was seen in the utility of the lipid biomarkers in predicting AsVD (except when female kidney disease patients were analysed separately). The odds of AsVD was more than 11-fold increased in patients who had hypertension attributable CKD with high risk APOL1 variants, [OR 11.85, 95 % CI – (1.08 – 129.91), p = 0.043]; this relationship was lost when all kidney disease patients, regardless of aetiology was used in the analysis, (OR 0.84 (95 % CI – 0.22 – 3.28; p – 0.802). Conclusion: Atherosclerotic vascular disease is common in kidney disease patients and most prevalent among PD patients compared to CKD stage 3, HD and KTRs. Dyslipidaemia and inflammation are common among kidney disease patients. Lipoprotein(a) predicted AsVD better than other lipid biomarkers (Lp-PLA2, APO A1) and lipid profile parameters (LDL-C, TG, TC). Age (> 40 years), male gender, low HDL-C and elevated Lp (a) independently predicted AsVD when all kidney disease patients were combined, while APOL1 risk variants independently predicted AsVD among patients with hypertension attributable kidney disease.
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    Assessment of GFR in the evaluation of potential living kidney donors at the Wits Donald Dordon Medical Center (WDGMC) and Charlotte Maxeke Johannesburg Academic Hospital (CMJAH)
    (2018) Okuthe, Jacktone Odhiambo
    Equations that estimate GFR (eGFR) are widely used in clinical practice to estimate kidney function in sub-Saharan Africa, but have not been validated for use in this region. This study assessed the performance of eGFR equations in adults evaluated for suitability for live kidney donation against a gold standard radionuclear GFR measurement (mGFR) and determined their usefulness for screening live kidney donors in South Africa. This study was a retrospective record review of 350 adults evaluated for living kidney donation from 1996 – 2013 at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and Wits Donald Gordon Medical Centre (WDGMC). Their eGFR was calculated using CG, 4-v MDRD and CKD-EPI equations. Plasma clearance of 51Cr-EDTA was used as a reference method for mGFR. The 4-v MDRD (with and without ethnicity adjustment) and the CKD-EPI (without ethnicity adjustment) equations underestimated the mGFR (negative bias of -8 mL/min/1.73m2, -16 mL/min/-1.73m2 and -6.4 mL/min/1.73m2 respectively).However, the bias associated with the average mGFR using the CG and CKD-EPI (with ethnicity adjustment) equations was not significant (2.3 mL/min/1.73m2 and 0.6 respectively).Use of the ethnicity factor resulted in overestimation of mGFR for both the 4v-MDRD equation (by 24.2ml/min/1.73m2 compared to 6.8 ml/min/1.73m2 without it) and the CKD-EPI equation (by 21.8ml/min/1.73m2, compared to 7.6ml/min/1.73m2, without the ethnicity factor). In conclusion, this study showed that almost half of adults screened for living donation in Johannesburg were not eligible due to comorbid hypertension, diabetes and unexplained kidney disease. In addition, the error statistics worsened as mGFR increased and all four prediction equations had a low sensitivity for determining individuals with a GFR <80 ml/min/1.73m2. Based on the findings in this study, use of a gold standard measured GFR should be the preferred method for assessing kidney function in potential living kidney donors in South Africa.
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    Modelling graft survival after kidney transplantation using semi-parametric and parametric survival models
    (2017) Achilonu, Okechinyere Juliet
    This study presents survival modelling and evaluation of risk factors of graft survival in the context of kidney transplant data generated in South Africa. Beyond the Kaplan-Meier estimator, the Cox proportional hazard (PH) model is the standard method used in identifying risk factors of graft survival after kidney transplant. The Cox PH model depends on the proportional hazard assumption, which is rarely met. Assessing and accounting for this assumption is necessary before using this model. When the PH assumption is not valid, modi cation of the Cox PH model could o er more insight into parameter estimates and the e ect of time-varying predictors at di erent time points. This study aims to identify the survival model that will e ectively describe the study data by employing the Cox PH and parametric accelerated failure time (AFT) models. To identify the risk factors that mediate graft survival after kidney transplant, secondary data involving 751 adults that received a single kidney transplant in Charlotte Maxeke Johannesburg Academic Hospital between 1984 and 2004 was analysed. The graft survival of these patients was analysed in three phases (overall, short-term and long-term) based on the follow-up times. The Cox PH and AFT models were employed to determine the signi cant risk factors. The purposeful method of variable selection based on the Cox PH model was used for model building. The performance of each model was assessed using the Cox-Snell residuals and the Akaike Information Criterion. The t of the appropriate model was evaluated using deviance residuals and the delta-beta statistics. In order to further assess how appropriately the best model t the study data for each time period, we simulated a right-censored survival data based on the model parameter-estimates. Overall, the PH assumption was violated in this study. By extending the standard Cox PH model, the resulting models out-performed the standard Cox PH model. The evaluation methods suggest that the Weibull model is the most appropriate in describing the overall graft survival, while the log-normal model is more reasonable in describing short-and long-term graft survival. Generally, the AFT models out-performed the standard Cox regression model in all the analyses. The simulation study resulted in parameter estimates comparable with the estimates from the real data. Factors that signi cantly in uenced graft survival are recipient age, donor type, diabetes, delayed graft function, ethnicity, no surgical complications, and interaction between recipient age and diabetes. Statistical inferences made from the appropriate survival model could impact on clinical practices with regards to kidney transplant in South Africa. Finally, limitations of the study are discussed in the context of further studies.
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