Hemoconcentration of Creatinine Minimally Contributes to Changes in Creatinine during the Treatment of Decompensated Heart Failure

Background Worsening serum creatinine is common during treatment of acute decompensated heart failure(ADHF). A possible contributor to creatinine increase is diuresis-induced changes in volume of distribution (VD)of creatinine as total body water (TBW) contracts around afixed mass of creatinine. Our objective was to better understand the filtration and non-filtration factors driving change in creatinine during ADHF. Methods Participants in the ROSE-AHF trial with baseline to 72-hour serum creatinine; net fluid output; and urinary KIM-1, NGAL, and NAG were included (n5270). Changes in VD were calculated by accounting form easured input and outputs from weight-based calculated TBW. Changes in observed creatinine (Crob served)were compared with predicted changes in creatinine after accounting for alterations in VD and non-steady state conditions using a kinetic GFR equation (Cr72HR Kinetic). Results When considering only change in VD, the median diuresis to elicit a$0.3 mg/dl rise in creatinine was27526 ml (IQR,25932 to29149). After accounting for stable creatinine filtration during diuresis, a change in VD alone was insufficient to elicit a >= 0.3 mg/dl rise in creatinine. Larger estimated decreases in VD were paradoxically associated with improvement in Crob served (r=20.18,P=0.003). Overall,23% of the change ineCr72HR Kinetic was attributable to the change in VD. A >= 0.3 mg/dl rise in eCr72HR Kinetic was not associated with worsening of KIM-1, NGAL, NAG, or post discharge survival (P.0.05 for all). Conclusions During ADHF therapy, increases in serum creatinine are driven predominantly by changes infiltration, with minimal contribution from change in VD.