Nephroprotective effect of cilastatin in allogeneic bone marrow transplantation. Results from a retrospective analysis.
Cilastatin, an inhibitor of the tubular brush border enzyme dehydropeptidase-I, is added in a fixed combination to imipenem. Cilastatin has been demonstrated in different animal models and in one clinical trial, to reduce the nephrotoxicity associated with cyclosporin A. To evaluate a possible nephroprotective effect of cilastatin following allogeneic BMT we conducted a retrospective analysis of 104 patients transplanted in our BMT Unit from January 1991 to January 1995. Imipenem/cilastatin (I/C) was used in a non-randomized manner in 64 patients during this period. Acute renal failure (ARF) was diagnosed in 32 patients (30%). ARF was not associated with gender, sepsis, conditioning regimen, underlying disease, bilirubin, or age. VOD occurred in 12/32 (37.5%) of patients with ARF whereas it occurred in only 7/72 (9.7%) of patients without ARF (P < 0.0007). ARF was not correlated with use of aminoglycosides, vancomycin, ciprofloxacine, ceftazidime or amphotericin-B. However, 13 patients of 64 exposed to I/C (20.3%) developed ARF vs 19 of 40 patients (47.5%) who were not exposed to I/C (P < 0.003; OR 0.28). Stratified analysis and multiple logistic regression confirmed the I/C nephroprotective action. The mean cyclosporin A levels in the I/C group were significantly decreased (208.6 +/- 64.9) vs the non-I/C group (265 +/- 118). We conclude that these results suggest I/C may counteract acute cyclosporin A nephrotoxicity following BMT and further prospective clinical trials are needed to confirm if routine administration of cilastatine confers benefit in the BMT setting.
Gruss
E
E
Department of Nephrology, Universidad Autónoma de Madrid, Spain.
Tomás
J F
JF
Bernis
C
C
Rodriguez
F
F
Traver
J A
JA
Fernández-Rañada
J M
JM
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods* / Q000502:physiology; D015377:Cilastatin / Q000008:administration & dosage / Q000494:pharmacology*; D016572:Cyclosporine / Q000009:adverse effects / Q000037:antagonists & inhibitors; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007938:Leukemia / Q000628:therapy; D008297:Male; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D012189:Retrospective Studies; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D011480:Protease Inhibitors; D015377:Cilastatin; D015378:Imipenem; D016572:Cyclosporine