Cystatin C- versus Creatinine-Based Assessment of Kidney Function in Advanced Heart Failure: Insights from REVIVAL

Abstract

<h3>Purpose</h3> Advanced heart failure (AHF) is associated with muscle wasting, potentially leading to overestimation of kidney function using serum creatinine (sCr)-based estimated glomerular filtration rate (eGFRsCr). Since cystatin C (CysC)-based eGFR (eGFRCysC) is less influenced by muscle mass, higher eGFRsCr in relation to eGFRCysC may reflect sarcopenia. In a cohort of AHF pts, we investigated the association of eGFRCysC and eGFRsCr with a composite endpoint of ventricular assist device (VAD), urgent transplant, or death. We hypothesized that surrogates of sarcopenia (i.e. lower handgrip strength [HGS] and reduced functional capacity) would be associated with the difference between eGFRCysC and eGFRCr (eGFRdiff). <h3>Methods</h3> Among 400 pts enrolled in REVIVAL (Registry Evaluation of Vital Information for VAD in Ambulatory Life), 270 had concomitant CysC and sCr measures. eGFRdiff was calculated as eGFRCysC - eGFRsCr. HGS, peak oxygen consumption (VO2 max) and 6-minute walk test distance (6MWTd) were concurrently assessed. <h3>Results</h3> eGFRCysC reclassified 57% of the pts to different GFR categories and resulted in a higher prevalence of severe kidney dysfunction (Figure A). In adjusted models, for each standard deviation decrease in HGS, VO2 max and 6MWTd, eGFRdiff changed by -8, -3 and -3 ml/min/1.73m², respectively (all p<0.03). eGFRCysC had a stronger association with the composite endpoint than eGFRsCr (adjusted hazard ratio [aHR]: eGFRCysC 1.35, p=0.025; eGFRsCr: 1.18, p=0.23). Pts reclassified to more advanced kidney dysfunction when using eGFRCysC had an increased risk for the composite endpoint (aHR 1.82, p=0.006; Figure B). <h3>Conclusion</h3> In AHF pts, when compared with sCr, CysC strengthens the association between kidney function and a composite of VAD, urgent transplant, or death. Lower HGS and reduced functional capacity are associated with higher eGFRsCr in relation to eGFRCysC, suggesting that sCr-based assessment may overestimate kidney function in AHF pts with sarcopenia.