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 a fixed mass of creatinine. Our objective was to better understand the filtration and nonfiltration 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 (Cr _observed ) were compared with predicted changes in creatinine after accounting for alterations in VD and non-steady state conditions using a kinetic GFR equation (Cr _{72HR 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 to -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 Cr _observed ( r =-0.18, P =0.003). Overall, -3% of the change in eCr _{72HR Kinetic} was attributable to the change in VD. A ≥0.3 mg/dl rise in eCr _{72HR Kinetic} was not associated with worsening of KIM-1, NGAL, NAG, or postdischarge survival ( P >0.05 for all).
Conclusions: During ADHF therapy, increases in serum creatinine are driven predominantly by changes in filtration, with minimal contribution from change in VD.
Competing Interests: J.L. Asher reports receiving research funding from Sequana Medical and having consultancy agreements with Translational Catalyst. S.G. Coca reports having consultancy agreements with Axon, Bayer, CHF Solutions, 3ive, Renalytix, Reprieve Cardiovascular, Takeda, and Vifor; serving on the editorial boards of CJASN, JASN, and Kidney International; serving as an associate editor for Kidney360; receiving research funding from ProKidney, Renalytix, Renal Research Institute (RRI), and XORTX; having ownership interest in pulseData and Renalytix; having patents and inventions with Renalytix; and serving as a scientific advisor for, or member of, Reprieve Cardiovascular and Renalytix. Z.L. Cox reports receiving research funding from AstraZeneca and Cumberland Emerging Technologies. L.A. Inker reports serving in an advisory or leadership role for the Alport’s Foundation, Diametrix, and Goldfinch; serving as a member of the American Society of Nephrology, National Kidney Disease Education Program, and National Kidney Foundation; having consultancy agreements with Diamtrix and Tricida; receiving research funding (for the institution) from the National Institutes of Health, National Kidney Foundation, Omeros, Reata Pharmaceuticals, and Travere; and having consulting agreements with Omeros and Tricida. J.B. Ivey-Miranda reports serving on a speakers bureau for AstraZeneca, Boehringer Ingelheim, Merck, Moksha8, and Novartis. V.S. Rao reports having patents or royalties with Corvidia Therapeutics and having consultancy agreements with Translational Catalyst. J.M. Testani reports receiving research funding from Abbott, Boehringer Ingelheim, Bristol Myers Squibb, FIRE1, 3ive Labs, Lexicon Pharmaceuticals, Merck, Otsuka, Reprieve, Sanofi, and Sequana Medical; having consultancy agreements with, and receiving honoraria from, AstraZeneca, Bayer, Boehringer Ingelheim, BD, Bristol Myers Squibb, Cardionomic, Edwards Life Sciences, FIRE1, 3ive Labs, Lexicon Pharmaceuticals, Lilly, MagentaMed, Merck, Novartis, Otsuka, Precardia, Regeneron, Relypsa, Reprieve, Sanofi, Sequana Medical, Windtree Therapeutics, and W.L. Gore; having patents or royalties with Corvidia, Reprieve, and Yale University; and having ownership interest in Reprieve and Sequana Medical. F.P. Wilson reports serving on the editorial boards for the American Journal of Kidney Disease and CJASN; receiving research funding from Amgen, Boehringer Ingelheim, Vifor, and Whoop; being the owner of Efference; having other interests in, or relationships with, Gaylord Health Care (on the board of directors) and Medscape (medical commentator); and having consultancy agreements with Translational Catalyst. All remaining authors have nothing to disclose.
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