Serum creatinine and cystatin C‐based estimates of glomerular filtration rate are misleading in acute heart failure

• Main Authors: Jutta S. Swolinsky, Niklas P. Nerger, David M. Leistner, Frank Edelmann, Fabian Knebel, Enkhtuvshin Tuvshinbat, Caroline Lemke, Robert Roehle, Michael Haase, Maria Rosa Costanzo, Geraldine Rauch, Veselin Mitrovic, Edis Gasanin, Daniel Meier, Peter A. McCullough, Kai‐Uwe Eckardt, Bruce A. Molitoris, Kai M. Schmidt‐Ott
• Format: Article
• Language: English
• Published: Wiley 2021-08-01
• Series: ESC Heart Failure
• Subjects: Acute heart failure; Worsening kidney function; Acute kidney injury; CKD‐EPI formula; Measured GFR; Visible fluorescent injectate
• Online Access: https://doi.org/10.1002/ehf2.13404

Abstract Aims We aimed to test whether the endogenous filtration markers serum creatinine or cystatin C and equation‐based estimates of glomerular filtration rate (GFR) based on these markers appropriately reflect changes of measured GFR in patients with acute heart failure. Methods In this prospective cohort study of 50 hospitalized acute heart failure patients undergoing decongestive therapy, we applied an intravenous visible fluorescent injectate (VFI), consisting of a low molecular weight component to measure GFR and a high molecular weight component to correct for measured plasma volume. Thirty‐eight patients had two sequential GFR measurements 48 h apart. The co‐primary endpoints of the study were safety of VFI and plasma stability of the high molecular weight component. A key secondary endpoint was to compare changes in measured GFR (mGFR) to changes of serum creatinine, cystatin C and estimated GFR. Results VFI‐based GFR measurements were safe and consistent with plasma stability of the high molecular weight component and glomerular filtration of the low molecular weight component. Filtration marker‐based point estimates of GFR, when compared with mGFR, provided only moderate correlation (Pearson's r, range 0.80–0.88, depending on equation used), precision (r2, range 0.65–0.78) and accuracy (56%–74% of estimates scored within 30% of mGFR). Correlations of 48‐h changes GFR estimates and changes of mGFR were significant (P < 0.05) but weak (Pearson's r, range 0.35–0.39). Observed decreases of eGFR by more than 15% had a low sensitivity (range 38%–46%, depending on equation used) in detecting true worsening mGFR, defined by a >15% decrease in mGFR. Conclusions In patients hospitalized for acute heart failure, serum creatinine‐ and cystatin C‐based predictions performed poorly in detecting actual changes of GFR. These data challenge current clinical strategies to evaluate dynamics of kidney function in acute heart failure.