Nephrotoxicity of high and conventional dosing regimens of colistin: A randomized clinical trial

BACKGROUND: 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. METHODS: 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 and conventional dose 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. RESULTS: Mean±sd of the difference between baseline and day 10 Cys C levels in high dose and conventional dose groups were 1.61±0.90 and 1.32±0.48, respectively (P=0.30). Within group analysis showed increase in Cys C levels in both groups (P= 0.001), however, no significant difference in Cys C levels was seen in between groups analysis (P=0.13). Prevalence of AKI based on RIFLE criteria was 60% and 15% in high dose and conventional dose groups, respectively (P= 0.003). 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). CONCLUSION: 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.