[Renal failure following liver transplantation].
The cumulative incidence of chronic kidney disease after liver transplantation (LT) is on the order of 40 to 50% at 1 year and over 50% at 5 years, and that of pre-end-stage renal failure 5-10% at 1 year and 10-20% at 5 and 10 years. Several variables appear to be independently associated with onset of kidney failure: age, sex (male), ethnicity (non-Asian), low glomerular filtration rate (GFR) before transplantation, use of renal replacement therapy before LT, diabetes before LT, HCV carriage, postoperative onset of acute renal failure, the year of transplantation (before or after 1994). Various factors cause chronic kidney disease after LT. Calcineurin inhibitors, specifically cyclosporine and tacrolimus, but also diabetes, nephroangiosclerosis, previous use of hydroxyethylstarch, play a major role in the onset of postgraft kidney failure. It is generally agreed that the nephrotoxicity of calcineurin inhibitors is in part dose-dependent and that a reduction in the dose can improve renal function. Nonetheless, the lesions are in large part irreversible. Trials are required to test interventions early after the LT, as soon as the first signs of kidney failure appear. Moreover, although the effect is dose-dependent, the relation with blood concentration of the drug is very imperfect, so any intervention must reduce the dose and not just the concentration to improve renal function. The introduction of new immunosuppressive drugs that are not nephrotoxic, such as mycophenolate mofetil, mTOR inhibitors, and anti-CD25 monoclonal antibodies [basiliximab and daclizumab (withdrawn from the market)], allow primary or secondary prevention of nephrotoxicity, with a partial or complete reduction in calcineurin inhibitors. Other interventions useful to limiting kidney failure after LT are the correction of hypertension, diabetes, and hyperlipidemia.
Calmus
Yvon
Y
Service de chirurgie générale et digestive, Hôpital Cochin, AP-HP, Paris Cedex 14, France. Yvon.calmus@cch.aphp.fr
Pageaux
Georges
G
D065095:Calcineurin Inhibitors; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000209:etiology* / Q000517:prevention & control; D016031:Liver Transplantation / Q000009:adverse effects*; D012307:Risk Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents