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Thesis (M.S.)--University of Wisconsin-Madison, 1992. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 77-84).

No description available.

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Division of Nephrology Department of Internal Medicine School of Clinical Medicine Faculty of Health Sciences University of Witwatersrand 7th June, 2017 / Objective Renal transplantation is the ideal therapeutic option for patients that reach end-stage renal failure. However, patients require long term immunosuppression following surgical transplantation to prevent graft rejection [1,2,4]. Mycophenolate mofetil (MMF) had proven to be an effective immunosuppressant in transplant patients[8,9,10], although it is associated with an increase in gastrointestinal adverse effects, which may result in dose adjustment or termination of use [22]. There is a paucity of data regarding gastrointestinal side effects of MMF in South Africa. This study attempts to describe the incidence of gastrointestinal complications, incidence of dose adjustment and discontinuation of MMF due to side effects, to compare the incidence of GI complications between those that had prior gastrointestinal ailments and those that had no prior gastrointestinal ailments and finally to determine possible risk factors (age, gender, ethnicity, donor type, pre-transplant GI diagnosis, pre-transplant diabetes and combination of MMF with tacrolimus) of gastrointestinal adverse effects. Method Data was collected retrospectively from the file records of the renal transplant unit at CMJAH (Charlotte Maxeke Johannesburg Academic Hospital) on adult patients who had received kidney transplants between 1998 and 2010 and who had received MMF as part of the immunosuppressive regimen for at least the one year post-transplant. Relevant data was captured in an anonymous fashion on a collection sheet. Descriptive analysis of the data was carried out. Time-to-event data were analysed by Kaplan-Meier survival analysis. The assessment of the effect of prior gastrointestinal ailments, as well as risk factors, was carried out by Cox Proportional Hazards regression to estimate the Hazard Ratios. Results A total of 188 patients were included in the study group, which comprised 65.4% males and 32.4% females (2.1% missing data). The mean age at transplant was 38.1 years. The patients were predominantly black (69.1%). Donors were predominantly deceased donors. Of the 24.5% of donors who were living donors, 76.1% were related living donors, while the rest were non-related living donors. The majority of patients (82%) were induced with MMF dose of 2 grams per day. After 5 years, 13.8% of patients discontinued MMF while 86.2% of the patients were still on MMF. 48.1% had a dose adjustment due to gastrointestinal side effects. 61% of patients had had a diarrhoeal adverse event by 5 years. 21.8% of the patients had gastrointestinal side effects other than diarrhoea by 5 years. The combination of tacrolimus and MMF was found to be a significant risk factor for diarrhoeal adverse events (Hazard Ratio 1.82; 95% CI 1.21-2.73). Having a living donor graft reduced the chance of non-diarrhoeal gastrointestinal adverse event (Hazard Ratio 0.33; 95% CI 0.13-0.84, p<0.02). A trend towards significance was seen in living donors having less diarrhoeal events although it did not reach statistical significance (Hazard Ratio 1.32; 95% CI 0.87-2.00, p=0.20). Conclusion As far as the authors are aware, this is the first local study on MMF and GIT adverse effect. We found the combination of MMF and tacrolimus is associated with increased risk of having diarrhoeal adverse events, which is consistent with international data[34,35]. Living donor graft is associated with a lower risk of developing non-diarrhoeal gastrointestinal events. Although non-significant, data suggest the same trend favoring living donor graft with regards to diarrhoeal events. / MT2017

Ischaemia-reperfusion injury (IRI) has been identified as a major contributor to both short and long term kidney transplant failure. Experimental evidence from the literature suggests that Erythropoietin (EPO) is tissue protective, reducing both inflammation and apoptosis following IRI. We performed a randomised, double blind, placebo controlled trial examining the tissue protective effect of high dose EPO (100,000iu over 3 days) in 39 recipients of an extended criteria donor kidney or a non-heart-beating donor kidney. The primary endpoints of the study were difference in plasma and urinary biomarker levels (NGAL, IL-18 and KIM-1) in addition to changes in gene expression. Secondary endpoints included safety, clinical data and differences in metabolomics profiles. There was no difference detected between the treatment groups in terms of biomarkers, gene expression, metabolomics profiling or clinical parameters. No adverse events related to EPO therapy were recorded. In addition, we developed a cell model of kidney transplantation using primary tubulo-epithelial cells and HMEC-1 cells, with which to confirm the protective effects of EPO. Treatment with 50U/ml one hour prior to undergoing cold hypoxia resulted in the maximum degree of tissue protection, as measured using an MTT and an LDH assay. No evidence of EPO toxicity was demonstrated. Tubulo-epithelial cells expressed EPOR mRNA and protein. No CD131 receptor could be demonstrated. In summary, EPO confers tissue protection in a cell model of kidney transplantation but this has not been shown to occur in a clinical trial using high dose EPO in recipients of marginal donor kidneys.

A research report to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master Medicine in branch of Haematology / Donor specific crossmatching is performed prior to renal transplantation in order to determine the presence of pre-existing antibodies against donor HLA antigens which can result in hyperacute rejection. Flow cytometric crossmatching is reported in the literature to be a more sensitive and objective method of testing than the complement dependent cytotoxicity (CDC) method that is currently used in the Gauteng Province. A prospective analysis of the flow cytomeric crossmatch (FCXM) assay using the Luminex technology as the reference method was conducted. Forty-three samples were analysed. The T cell crossmatch (using a cutoff value of 2) revealed a sensitivity of 66.7%, a specificity of 83.8%, a positive predictive value (PPV) of 40% and negative predictive value (NPV) of 93.9%. The B cell crossmatch (using a cutoff value of 5) gave a sensitivity of 100%, specificity of 92.7%, and a PPV and NPV of 40 and100%, respectively. In addition, a retrospective analysis of clinical data for all patients transplanted during the period January 2008 to May 2009 was performed. Of a total of 50 patients assessed post transplant, none of the patients showed signs of hyperacute rejection, while twelve percent (12%) of patients revealed signs and symptoms suggestive of acute rejection. The validation of the flow cytometric crossmatch analysis was complex as there is no gold standard reference method. The assay was validated based on the clinical relevance of its high negative predictive value and the absence of hyperacute rejections in the clinical follow up. The rate of acute rejection found in this study is similar to that reported in literature.

Thesis (M.S.)--University of Wisconsin--Madison, 1982. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 54-59).

Current immunogenetic tests before organ transplantation include HLA typing and detection of HLA-specific antibodies. However, these tests do not provide information about the B cells participating in the humoral response against the transplanted organ. BAFF (B activating factor) plays an important role in the proliferation, maturation and differentiation of B cells. A soluble form of the cytokine arises after splicing the membrane form of BAFF. The soluble cytokine binds to three types of receptors - TACI, BCMA and BCMA. Some recent studies suggest that BAFF could serve as a marker or predictor of antibody-mediated (humoral) rejection in kidney transplant recipients. Our study consists of two parts. The first part is focused on the detection of soluble BAFF levels in patients after renal transplantation. The aim of our study was therefore to correlate levels of soluble BAFF cytokine in patients before and after transplantation with the clinical course and incidence of rejection after transplantation. The study included 92 kidney recipients. Humoral rejection was diagnosed on the basis of a positive finding of C4d deposits in peritubular capillaries (imunoflorescenční detection), and the presence of donor- specific antibodies. BAFF levels were determined using Xmap methodology by the Luminex method...

INTRODUCTION Cardiovascular diseases (CVD) are more common in kidney transplant recipients (KTRs) than in the general population. The high incidence of CVD in the KTRs can be attributed to traditional risk factors, additional risk factors associated with graft dysfunction and those specifically related to transplantation. Carotid intima-media thickness (cIMT) is a proven surrogate of atherosclerosis; it correlates with vessel pathology and is precisely imaged using ultrasound technology. This study was aimed at determining the prevalence and predictors of cardiovascular risk among KTRs at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) and to examine the relationship between cardiovascular risk factors and carotid intima media thickness. METHODS Patients aged 18 years and above who received a kidney transplant at the CMJAH between January 2005 and December 2009 were recruited. A questionnaire that captured cardiovascular risk factors was administered. Patients records were assessed for information on their post transplant follow up. All patients had echocardiography and carotid doppler done for measurement of intima-media thickness. The Framingham Risk Score was used to categorize patients into low, moderate, high risk and very high risk groups. Results were analyzed using statistical package for social sciences (SPSS) version 17, p value of 0.05 was considered significant. RESULTS One hundred (KTRs) 63 male (63%) and 37 female (37%) were recruited ranging in age from 19 to 70 years, with a mean age of 42.2 ± 12.42. Thirty six patients (36%) were found to have high cardiovascular risk. Multiple regression showed proteinuria (p = 0.022), higher cumulative steroid dosage (p = 0.028), elevated serum triglycerides (p = 0.04) and the presence of plaques in the carotid artery (p = 0.012) as predictors of higher cardiovascular risk.Carotid intima-media thickness correlates with higher CVD risk. Fourteen patients (14%) had a carotid artery plaque. Twenty five patients (25%) had cIMT of >0.7 mm. CONCLUSION Kidney transplant recipients in CMJAH were found to have high cardiovascular risk (36%) and carotid intima-media thickness correlates with this high CVD risk. Routine follow up of KTRs should include measurement of cIMT as it provides a simple non-invasive assessment of subclinical atherosclerosis.