Jutta S Swolinsky1, Niklas P Nerger1, David M Leistner2,3,4, Frank Edelmann3,4,5, Fabian Knebel6, Enkhtuvshin Tuvshinbat1, Caroline Lemke1, Robert Roehle3,7,8, Michael Haase9, Maria Rosa Costanzo10, Geraldine Rauch3,7, Veselin Mitrovic11, Edis Gasanin11, Daniel Meier12, Peter A McCullough13, Kai-Uwe Eckardt1, Bruce A Molitoris14, Kai M Schmidt-Ott1,3,15. 1. Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. 2. Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Benjamin Franklin, Berlin, Germany. 3. Clinical Research Unit, Berlin Institute of Health (BIH) at Charité - Universitätsmedizin Berlin, Berlin, Germany. 4. DZHK (German Centre for Cardiovascular Research) Partner Site Berlin, Berlin, Germany. 5. Department of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Virchow Klinikum, Berlin, Germany. 6. Department of Cardiology and Angiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Campus Mitte, Berlin, Germany. 7. Institute of Biometry and Clinical Epidemiology, Charité - Universtitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. 8. Coordinating Center for Clinical Studies, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany. 9. Faculty of Medicine, Otto von-Guericke-University Magdeburg, Magdeburg, Germany. 10. Advocate Heart Institute, Naperville, IL, USA. 11. Department of Cardiology, Kerckhoff Klinik, Bad Nauheim, Germany. 12. FAST BioMedical, Indianapolis, IN, USA. 13. Baylor University Medical Center, Baylor Heart and Vascular Hospital, Baylor Heart and Vascular Institute, Dallas, TX, USA. 14. School of Medicine, Indiana University, Indianapolis, IN, USA. 15. Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
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.
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 failurepatients 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.
Authors: Jutta S Swolinsky; Enkhtuvshin Tuvshinbat; David M Leistner; Frank Edelmann; Fabian Knebel; Niklas P Nerger; 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 Journal: ESC Heart Fail Date: 2021-12-08