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.
Department of Nephrology, Universidad Autónoma de Madrid, Spain.
E
E
Gruss
J F
JF
Tomás
C
C
Bernis
F
F
Rodriguez
J A
JA
Traver
J M
JM
Fernández-Rañada
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