Cystatin C and the difference between cystatin C and serum creatinine: Improved metrics to predict waitlist mortality among decompensated cirrhosis patients

Introduction: Among decompensated cirrhosis patients, serum creatinine (sCr) is biased by sex, frailty, and hepatic synthetic function, while Cystatin C (cysC) is not. We that sCr would better associate with waitlist mortality and that the difference between cysC and sCr (cysCsCr diff ) would quantify this bias and be independently associated with outcomes. Methods: We measured cysC levels at ambulatory liver transplant visits among 525 consecutive patients seen at our center. We defined the cysCsCr diff as the difference between cysC minus sCr. We compared demographics and clinical characteristics in patients with low, intermediate, and high cysCsCr diff , divided by tertile. We used Cox regression to compare the association between sCr and cysC and waitlist mortality and demonstrate the independent association between cysCsCr diff and waitlist mortality. Results: In Cox regression, cysC was significantly more associated with waitlist mortality than sCr ( p <0.001). We found that as compared to those with a low cysCsCr diff , those with an intermediate or high cysCsCr diff were more likely to be female, have ascites, have higher frailty, and have higher MELD 3.0 scores ( p <0.05 for all). Compared to those with a low cysCsCr diff , we found that those in the intermediate and high groups were more likely to die during follow-up (Low–6% v. Intermediate–8% v. High–11%, p =0.007). We found that after adjusting for the components of the MELD 3.0 score, each 1-point increase in the cysCsCr diff was associated with 1.72x (1.27–2.32) the hazard of waitlist mortality. Discussion: Our study demonstrates that not only is cysC more associated with waitlist mortality than sCr, but that cysCsCr diff represents a novel independent metric associated with waitlist mortality.