Identification of Variables to Estimate the Risk of Amphotericin B (AmB)-Induced Nephrotoxicity in the Multiple Myeloma (MM) Bone Marrow Transplantation (BMT) Population.



BMT recipients with MM are at risk for developing both life threatening invasive mycoses (i.e. Aspergillosis, Fusariosis) and significant renal impairment secondary to their disease. AmB deoxycholate has been the sole agent for prevention or treatment of these infections, but it is nephrotoxic (NT). Comparatively, lipid AmB (L-AmB) formulations are nephro-sparing, but their widespread use can produce significant economic burdens. AmB induced NT is hard to predict, consequently, MM patients who would benefit most from the nephro-sparing effects of L-AmB are difficult to identify. The purpose of this retrospective study is to determine variables that can be used to develop a predictive model to identify MM patients at risk for AmB-induced NT apriori. Medical records of 49 MM patients undergoing BMT prior to 1996, who received at least two consecutive days of AmB therapy were reviewed. NT was defined as a doubling of the serum creatinine (Scr) from day 1 of treatment. Using either a [CHI] or Student's t-test, NT and nonnephrotoxic (NNT) patients were compared for: age, sex, weight, concomitant NT drugs, AmB indication (prophylaxis, empiric, or documented infection), AmB daily and total dose, length of AmB therapy, BMT type and protocol, electrolyte status, pre-hydration, baseline Scr, and estimated creatinine clearance (CrCl). There were 19 (39%) NT and 30 (61%) NNT patients. Both groups were comparable in mean age (51.5 +/- 6.8 yrs) and predominately male (NT=68%; NNT=70%). Compared to NTT patients, NT patients were more likely to have received a total AmB dose >= 7.0mg/kg (p=0.05), >= 21days of AmB exposure (p=0.04) and pressor and inotrope support (p=0.0003). No significant differences were observed between groups with regard to AmB indication, incidence of electrolyte abnormalities; use of pre-hydration; baseline Scr and CrCl; BMT type or protocol; and daily AmB doses. There were also no significant difference in these variables between the groups on the first day of AmB use. In conclusion, many MM patients who received AmB did not develop AmB induced NT. There were few significant differences between NNT and NT patients. Variables which may ultimately predict AmB induced NT and help identify MM BMT patients who will benefit most from L-AmB, include cumulative doses in excess of 7mg/kg, AmB exposure in excess of 21 days, and the concomitant use of pressor/inotropic support.

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38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th