Effect of cilastatin on cyclosporine-induced acute nephrotoxicity in kidney transplant recipients.
BACKGROUND
Cyclosporine (CsA)-induced acute nephrotoxicity could be reduced by prevention of parenchymal accumulation of the drug itself. The objective of this prospective study was to evaluate whether cilastatin, an inhibitor of active tubular resorption of CsA, reduces CsA-induced acute nephrotoxicity in kidney graft recipients.


METHODS
Sixty-nine kidney recipients with immediate graft functional recovery were randomly assigned to either the treatment group (imipenem/cilastatin, n=33) or the control group (ceftazidime, n=36). All patients followed a standard immunosuppressive regimen based on CsA and low-dose prednisone. Graft function and CsA levels were evaluated 3, 5, 10, 15, and 30 days after transplantation.


RESULTS
Compared with the control group, imipenem/cilastatin administration reduced the serum creatinine level in the first 2 weeks after transplantation, reaching a significant effect on postoperative day 10 (P<0.05). No significant differences were demonstrated between the two groups for CsA levels, patient and graft survival, and all the other examined parameters.


CONCLUSIONS
Our findings support the hypothesis that cilastatin administration can reduce CsA-induced acute nephrotoxicity after kidney transplantation.
Carmellini
M
M
Instituto di Chirurgia Generale e Sperimentale, Università degli Studidi Pisa, Ospedale di Cisanello, Italy.
Frosini
F
F
Filipponi
F
F
Boggi
U
U
Mosca
F
F
D000208:Acute Disease; D000328:Adult; D002102:Cadaver; D015377:Cilastatin / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced*; D016030:Kidney Transplantation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000494:pharmacology*
D011480:Protease Inhibitors; D015377:Cilastatin; D016572:Cyclosporine; D003404:Creatinine