Switching from cyclosporine to tacrolimus in patients with chronic transplant dysfunction or cyclosporine-induced adverse events.
BACKGROUND
Progressive renal-function decline caused by chronic allograft nephropathy is the main cause of long-term failure after kidney transplantation. Moreover, chronic cyclosporine (CsA)-induced nephrotoxicity is an important nonimmunologic factor contributing to graft dysfunction and loss, and adverse events may require CsA withdrawal.


METHODS
Tacrolimus (Tac) replaced CsA-based immunosuppression in 133 transplant patients (114 kidney, 15 kidney-pancreas, 4 pancreas after kidney) with progressive loss of renal function (71% of patients) or CsA intolerance (29% of patients) not responding to CsA dose-lowering. The primary end-points of this prospective study focusing on renal function were the safety and efficacy of Tac immunosuppression.


RESULTS
Tac was generally well tolerated but definitively withdrawn for 23 (17%) patients (21 graft failures, 1 case of diabetes, and 1 case of clinical intolerance). Differential creatinemia (creatinemia-nadir creatinemia after transplantation) decreased significantly from 85.4+/-9.8 to 39.0+/-7.5 mumol/L (P<0.001; mean+/-SEM) after 1 year and 3.6+/-18.1 mumol/L (P<0.01) after 4 years. For patients with CsA intolerance, switch to Tac improved intolerance symptoms in all cases. Blood urea, creatinine clearance, blood total cholesterol, and triglycerides improved significantly, and the percentage of hypertensive patients remained stable with no de novo hypertension. During follow-up, one patient experienced an acute rejection episode (not histologically proven), and four died. Twenty-one (16%) transplants failed, significantly more frequently in patients with advanced renal impairment before Tac (P<0.0001).


CONCLUSIONS
Switching from CsA to Tac can be an alternative strategy in kidney-transplant patients suffering from chronic allograft dysfunction or CsA toxicity. The persistently improved renal function over several months of evaluation suggests that in these patients, Tac might be less nephrotoxic than CsA and could prolong transplant function despite CsA failure.
Cantarovich
Diego
D
ITERT, Institut de Transplantation et de Recherche en Transplantation, Service de Néphrologie et d'Immunologie Clinique, Centre Hospitalier et Universitaire de Nantes, Nantes, France. diego.cantarovich@chu-nantes.fr
Renou
Muriel
M
Megnigbeto
Alexandre
A
Giral-Classe
Magali
M
Hourmant
Maryvonne
M
Dantal
Jacques
J
Blancho
Gilles
G
Karam
Georges
G
Soulillou
Jean-Paul
JP
D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011446:Prospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus