CME on Transplantation is dedicated to online CME conferences, courses and presentations (slides with voice over) on transplantation, given by local and international experts. Its mission is to keep you up-to-date with the most recent developments on transplantation.
Presentation
"Calcineurin Inhibitor Drug-Free Kidney Transplantation" Dr. Stuart M. Flechner (biography) English - 2003-05-12 - 50 minutes
(42 slides)
Summary : This talk will focus on current problems in transplantation and offer a novel immunosuppressive solution to some of these problems. First of all there aren’t enough organs available for transplantation, and secondly, not enough is known about diagnosing and treating chronic allograft nephropathy. We’ve seen from North American data that the survival half-life for patients with acute rejection hasn’t changed much in 10 years, whereas that of patients without acute rejection has improved (NEJM 2000. 342: 610). The goal is therefore to not have acute rejection.
Within the last few years we’ve moved towards a standard three-drug regimen of a calcineurin inhibitor, an antiproliferative agent, plus a steroid, which coupled with an induction antibody reduces the rate of acute rejection. Renal function has been studied as a risk factor for chronic renal allograft rejection, with SCr levels > 2 at 6 months found to be associated with increased risk. (Flechner et al. 1996. Transplantation. 61: 1235). Hariharan et al recently demonstrated a stepwise reduction in cadaveric kidney transplant survival with every 0.5mg increase in creatinine (Kidney International. 2002. 62: 311-18).
One of a variety of factors contributing to chronic allograft nephropathy is the use of nephrotoxic drugs. Calcineurin inhibitors like cyclosporin (with tacrolimus) are known to cause vasoconstriction of the pre-glomerular arterioles, leading to diminished renal blood flow and glomerular filtration. Khanna et al have also recently shown the expression of TGF-B and fibrogenic genes in transplant recipients with Tac and CsA nephrotoxicity (Kidney International. 2002. 62: 2257-63). Early evidence of diminished renal function in patients taking CsA was seen 20 years ago, with SCr levels around 2 mg/dl (Flechner et al. 1983.Transplant Proc. 15: 2689).
Sirolimus was originally developed with the intention of use with an early calcineurin inhibitor, and was tested in cyclosporin based regimens. This left much to be desired in terms of acute rejection rates and SCr levels. Hence came the introduction of induction antibodies to a calcineurin inhibitor-free regimen, in order to try to achieve lower acute rejection rates and better renal function. Here we will take a look at the data from recent calcineurin inhibitor –free studies with Sirolimus (SRL+MMF+steroids following Basiliximab) which show improved renal function, and also preliminary data that show the combination of MMF and SRL to prevent renal allograft nephropathy.
Learning objectives : The participant will:
- review the history of immunosuppressive therapies and their performance in terms of acute rejection and renal function.
- review data on calcineurin inhibitor free regimens which show improved renal function; and preliminary data showing a (SRL +MMF) regimen to prevent renal allograft nephropathy.
