colistin and Hypoalbuminemia

This study aimed to assess the predictors of acute kidney injury (AKI) during colistin therapy in a cohort of patients with bloodstream infections (BSI) due to colistin-susceptible Gram-negative bacteria, focusing on the role of serum albumin levels. The study consisted of two parts: (1) a multicentre retrospective clinical study to assess the predictors of AKI during colistin therapy, defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and (2) bioinformatic and biochemical characterization of the possible interaction between human serum albumin and colistin. Among the 170 patients included in the study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable analyses, serum albumin <2.5 g/dL was independently associated with K1-AKI (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17-2.93, p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15-4.87, p = 0.019). Bioinformatic and biochemical analyses provided additional information nurturing the discussion on how hypoalbuminemia favors development of AKI during colistin therapy. In conclusion, severe hypoalbuminemia independently predicted AKI during colistin therapy in a large cohort of patients with BSI due to colistin-susceptible Gram-negative bacteria. Further study is needed to clarify the underlying causal pathways.

Topics: Acute Kidney Injury; Anti-Bacterial Agents; Colistin; Computational Biology; Female; Humans; Hypoalbuminemia; Incidence; Male; Models, Molecular; Molecular Conformation; Retrospective Studies; Sepsis; Serum Albumin, Human; Severity of Illness Index; Structure-Activity Relationship

Since multidrug-resistant gram-negative organisms have been increasing, polymyxin E (colistin) has been reintroduced despite its nephrotoxicity. A case-control study was performed to investigate the incidence, clinical characteristics and risk factors of colistin-induced nephrotoxicity. From August 2006 to June 2008, 47 cases receiving at least one defined daily dose (DDD) of intravenous colistin were included; 15 (31.9%) of the 47 cases developed nephrotoxicity with preserved urine output, 3 (20%) of whom underwent renal replacement therapy. The mean dosage of colistimethate sodium was 2.25 g (22.5 DDD; range 0.6-8.7 g) at the time of nephrotoxicity. Of 10 patients who were re-assessed for renal function after 1 month, 9 (90%) recovered their renal function. In the univariate analysis, site of infection, hypoalbuminaemia and cumulative dosage of the second-generation fluoroquinolones, aminoglycosides and non-steroidal anti-inflammatory drugs (NSAIDs) co-administered during colistin treatment as well as concomitant use of NSAIDs were risk factors for nephrotoxicity. However, in the logistic regression hypoalbuminaemia and the use of NSAIDs were significant risk factors for increased nephrotoxicity during colistin administration, suggesting that free colistin might cause renal toxicity. In conclusion, colistin-induced nephrotoxicity occurred at a high rate, and hypoalbuminaemia and concomitant use of NSAIDs were significant risk factors.

Topics: Adult; Aged; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Colistin; Female; Gram-Negative Bacterial Infections; Humans; Hypoalbuminemia; Incidence; Kidney; Kidney Diseases; Male; Middle Aged; Risk Factors