Nephrotoxicity is a known adverse effect of PMB. Animal data suggests that once daily dosing may be associated with decreased rate, severity and more gradual onset of nephrotoxicity compared to divided dosing. Clinical data evaluating the effect of PMB dosing frequency on the nephrotoxicity is limited.
In a single center, retrospective study we evaluated adult patients with Creatinine Clearance (CrCl) ≥30 mL/min who received ≥48h of PMB therapy. Nephrotoxicity was defined as development of acute kidney injury (AKI) using RIFLE criteria. The primary objective was to compare rate of AKI with PMB once vs. twice daily dosing. Secondary endpoints included in-hospital mortality and time to AKI.
From 347 hospitalized patients who received PMB (Jan 2008 – Oct 2015), 173 were included (once daily n=141, twice daily n=32). Median age was 68 years (IQR 56-79), CrCl was 65 mL/min (IQR 44-91), mAPACHE II score was 14 (12-16), PMB duration of therapy was 6 days (IQR 4-11), 59% of patients received concomitant nephrotoxic agents, and these were comparable between once and twice daily dosing. More patients received total dose >1,500,000 units/day (57 vs. 13%, P=0.0005) and an initial median dose was higher (21,930 vs. 16,253 units/kg/day, P=0.0005) with once vs. twice daily dosing. Rate of AKI was 43% with once vs. 22% with twice daily dosing, P=0.04 with most cases being Risk category by RIFLE (18 vs. 16%, P=0.9). No patients met ESRD. In-hospital mortality was 19% with once vs. 28% with twice daily dosing, P=0.4. Time to AKI onset (7 vs. 8 days) and peak serum creatinine (SCr) (8 vs. 8 days) was similar with once vs. twice daily dosing. In patients who developed AKI (n=68), there was no difference in PMB exposure before AKI (6,200,000 with once vs. 8,500,000 units twice daily dosing, P=0.9), and 35 out of 39 patients with subsequent SCr available for evaluation had SCr decreased.
In multivariate model, severe sepsis (OR 4.2, 95% CI 1.6-11.3, P=0.005), receipt of >2 concomitant nephrotoxic agents (OR 2.6, 95% CI 1.0-6.7, P=0.045), PMB duration of therapy >10 days (OR 2.6, 95% CI 1.0-4.5, P=0.02) and total dose >1,500,000 units/day (OR 2.1, P=0.05) were identified as an independent predictors of AKI, but not once daily dosing (OR 2.6, 95% CI 0.9-7.1, P=0.075).
Conclusion: Observed nephrotoxicity was higher in the once daily group, however these events were multifactorial and most patients had recovery of renal function.
J. Papadopoulos, None
D. Eiras, None
Y. Dubrovskaya, None