Hemoconcentration of creatinine minimally contributes to changes in creatinine during treatment of decompensated heart failure

Abstract

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 a fixed 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 (n= 270). Changes in VD were calculated by accounting for measured input and outputs from weight-based calculated TBW. Changes in observed creatinine (Crobserved) were compared to 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 was -7526 mL (IQR, -5932, -9149). 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 Crobserved (r=-0.18, p=.003). Overall, -3.3% of the change in Cr72HR Kinetic was attributable to the change in VD. A ≥0.3 mg/dL rise in Cr72HR Kinetic was not associated with worsening of KIM-1, NGAL, NAG, or post discharge survival (p>.05 for all). Conclusions: During ADHF therapy, increases in serum creatinine are driven predominantly by changes in filtration with minimal contribution from change in VD.