Cystatin C- vs. Creatinine- Based Assessment of Renal Function in Patients Admitted with Heart Failure: Insights from DOSE, ROSE and CARRESS-HF

Abstract

<h3>Purpose</h3> Reduction in serum creatinine (sCr) generation due to muscle wasting, which is commonly observed in heart failure (HF), may lead to overestimation of renal function using sCr-based equations. Cystatin C (CysC) is an endogenous protease inhibitor that is produced by all nucleated cells and, in contrast to sCr, is less influenced by muscle mass. Prolonged or recurrent hospitalizations may promote muscle wasting and further undermine the accuracy of sCr-based estimated glomerular filtration rate (eGFR). We compared CysC- and sCr-based eGFR in pts admitted with HF at serial time points before and after discharge. <h3>Methods</h3> We pooled data from 3 trials performed in pts admitted with HF (DOSE, ROSE and CARRESS-HF). eGFR was calculated using CysC- (eGFR_CysC) and sCr- (eGFR_sCr) CKD-EPI equations. The discrepancy between eGFR_CysC and eGFR_sCr was calculated as ΔeGFR = (eGFR_CysC-eGFR_sCr)/ eGFR_sCr. Linear mixed models regressed ΔeGFR at multiple time points. In a subset of 301 pts sampled after discharge, we investigated the association of ΔeGFR at 60 days with a composite of prolonged initial HF admission (length of stay ≥ 10 days) or subsequent readmission. <h3>Results</h3> 2849 samples were available in 841 pts (age 68 ± 13, 26% F, ejection fraction 36 ± 17%). Compared with eGFR_sCr, eGFR_CysC reclassified 50% of the samples to different eGFR categories, mainly to more advanced renal dysfunction (<b>Fig A</b>). ΔeGFR widened during HF admission and remained significantly different at 60-day follow-up when compared to the day of admission (<b>Fig B</b>). Pts who experienced prolonged initial HF admission or subsequent readmission had wider ΔeGFR at 60 days (p<0.001). <h3>Conclusion</h3> CysC reclassifies a large proportion of pts admitted with HF to more advanced renal dysfunction when compared to sCr. The discrepancy between CysC- and sCr-based eGFR accentuates during HF admission and is sustained at 60-day follow-up, particularly in pts with prolonged or recurrent hospitalizations.