Nephrotoxicity of High and Conventional Dosing Regimens of Colistin: A Randomized Clinical Trial

Nephrotoxicity has been a major long-standing concern about colistin.This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin. A randomized open-labeled clinical trial on 40 patients with multi-drug resistant gram negative infections was designed. Patients were allocated into two equal-size groups receiving high (a loading dose of 9 million international units (MIU) and maintenance doses of 4.5 MIU every 12 h) and conventional dose (2 MIU every 8 h) of colistin. Blood samples were taken on day 1, 3, 5, 7 and 10 of treatment for measuring serum cystatin C (Cys C) levels. Incidence of acute kidney injury (AKI) was also evaluated based on RIFLE criteria. Mean ± sd of the difference between baseline and day 10 Cys C levels in high dose and conventional dose groups were 1.610.90 ± and 1.320.48 ± , respectively (P0.30 = ). Within group analysis showed increase in Cys C levels in both groups (P0.001 = ),however, no significant difference in Cys C levels was seen in between groups analysis (P0.13 = ). Prevalence of AKI based on RIFLE criteria was 60% and 15% in high dose and conventional dose groups, respectively (P0.003 = ). Comparison of Cys C between AKI (mean ± sd) and non-AKI (mean ±sd) patients, irrespective of colistin dosage regimens, confirmed a significant difference (P 0.0001 <). Although, colistin-induced nephrotoxicity, determined by Cys C levels, was not confirmed by our findings, however, higher incidence of AKI in high-dose group, defined by RIFLE criteria, along with higher levels of Cys C in AKI patients are supportive of the higher risk of renal toxicity associated with high-dose regimen of colistin. More RCTs with a larger sample size are recommended.