NEPHROPROTECTIVE EFFECT OF CILASTATIN IN ALLOGENEIC BONE-MARROW TRANSPLANTATION - RESULTS FROM A RETROSPECTIVE ANALYSIS

Cilastatin, an inhibitor of the tubular brush border enzyme dehydropep tidase-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 evalu ate a possible nephroprotective effect of cilastatin following allogen eic BMT we conducted a retrospective analysis of 104 patients transpla nted in our BMT Unit from January 1991 to January 1995. Imipenem/cilas tatin (I/C) was used in a non-randomized manner in 64 patients during this period. Acute renal failure (ARF) was diagnosed in 32 patients (3 0%). 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 patien ts without ARF (P < 0.0007). ARF was not correlated with use of aminog lycosides, 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 UC nephroprotective action. The mean cyclosporin A levels in the I/C g roup were significantly decreased (208.6 +/- 64.9) vs the non-I/C grou p (265 +/- 118). We conclude that these results suggest I/C may counte ract acute cyclosporin A nephrotoxicity following BMT and further pros pective clinical trials are needed to confirm if routine administratio n of cilastatine confers benefit in the BMT setting.