Sirolimus does not exhibit nephrotoxicity compared to cyclosporine in renal transplant recipients.
Sirolimus and cyclosporine (CsA) prevent acute rejection in man when used as primary therapies in triple drug regimens. Sirolimus does not act via the calcineurin pathway and therefore is not expected to produce the same renal side-effects. This paper presents the pooled 2-year data analysis of renal function parameters from two open-label, randomized, multicenter studies. Patients (18-68 years) receiving a primary renal allograft were randomized to receive concentration-controlled sirolimus (n = 81) or CsA (n = 80), in combination with azathioprine and steroids (n = 83), or mycophenolate mofetil (MMF) and steroids (n = 78). From week 10 through year 2, calculated glomerular filtration rate (GFR) was significantly higher in sirolimus--than in CsA-treated patients (69.3 vs. 56.8 mL/min, at 2 years, p = 0.004). Serum uric acid was significantly higher in the CsA-treated patients and magnesium was significantly lower; these parameters were more likely to be within normal limits in the sirolimus group. Mean serum potassium and phosphorus were lower in sirolimus-treated patients. In conclusion, sirolimus, when administered as primary therapy in combination with azathioprine or MMF, has a favorable safety profile compared to CsA with regards to renal function.
Hospital 12 de Octubre, Madrid, Spain. jmorales@h120.es
José M
JM
Morales
Lars
L
Wramner
Henri
H
Kreis
Dominique
D
Durand
Josep M
JM
Campistol
Amado
A
Andres
Joaquin
J
Arenas
Eric
E
Nègre
James T
JT
Burke
Carl G
CG
Groth
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D017322:Clinical Trials, Phase II as Topic; D016572:Cyclosporine / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000494:pharmacology / Q000633:toxicity*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus