[Truncated abstract] Renal transplantation is the best form of renal replacement therapy for patients with end-stage kidney disease. Refinements in immunosuppressive treatments and new immunology techniques have reduced early rejection episodes and improved the short term survival of renal allografts. Patients with successful renal transplant remain at high risk of long-term cardiovascular complications which may be mediated, in part, by hyperlipidaemia, hypertension and diabetes. The rate of late allograft loss due to cumulative immune and non-immune mediated injury (defined as chronic allograft nephropathy - 'CAN') remains largely unchanged. The immunosuppressive drugs known as the calcineurin inhibitors (CNI) and the mTOR inhibitors (mammalian Target of Rapamycin inhibitors "mTOR-I") may have effects upon the potential non-immune mediators of CAN (glucose metabolism, lipid profile, proteinuria and blood pressure), which are also significant cardiovascular risk factors. This thesis uses retrospective and prospective studies to test the hypothesis that in renal transplant recipients (RTR) with histological evidence of CAN, the non-immune mediators of CAN especially proteinuria and/or histological characteristics of allograft injury determined by BANFF criteria, determine whether the conversion from a CNI to a mTOR-I is associated with improved renal function. It also tests whether despite an improvement in renal function there are any potentially adverse effects upon glucose and lipid metabolism. Study 1 retrospectively examined the effects of the mTOR-I, Sirolimus (SRL) upon changes in renal allograft function measured as estimated Glomerular Filtration Rate (eGFR) and proteinuria and determined the relationship between pre conversion renal histology and post conversion eGFR & proteinuria to identify clinical and histological predictors of successful conversion to SRL from a CNI.
|Publication status||Unpublished - 2012|