Cystatin C and Muscle Mass in Patients With Heart Failure

Abstract

Background: The estimated glomerular filtration rate (eGFR) from cystatin C (eGFRcys) is often considered a more accurate method to assess GFR compared with an eGFR from creatinine (eGFRcr) in the setting of heart failure (HF) and sarcopenia, because cystatin C is hypothesized to be less affected by muscle mass than creatinine. We evaluated (1) the association of muscle mass with cystatin C, (2) the accuracy of eGFRcys, and (3) the association of eGFRcys with mortality given muscle mass.

Methods and results: We included 293 patients admitted with HF. Muscle mass was estimated with a validated creatinine excretion-based equation. Accuracy of eGFRcys and eGFRcr was compared with measured creatinine clearance. Cystatin C and creatinine were 31.7% and 59.9% higher per 14 kg higher muscle mass at multivariable analysis (both P < .001). At lower muscle mass, eGFRcys and eGFRcr overestimated the measured creatinine clearance. At higher muscle mass, eGFRcys underestimated the measured creatinine clearance, but eGFRcr did not. After adjusting for muscle mass, neither eGFRcys nor eGFRcr were associated with mortality (both P > .19).

Conclusions: Cystatin C levels were associated with muscle mass in patients with HF, which could potentially decrease the accuracy of eGFRcys. In HF where aberrations in body composition are common, eGFRcys, like eGFRcr, may not provide accurate GFR estimations and results should be interpreted cautiously.

Keywords: Heart failure; cystatin C; glomerular filtration rate; muscle mass.

Fig. 1.

Association of cystatin C and creatinine with muscle mass. After adjusting for mClcr, age, sex and race, muscle mass showed a positive association with both creatinine and cystatin C (both P < .001). The red line and the dashed orange line represent the association of log transformed muscle mass (restricted cubic spline) with log-transformed cystatin C and creatinine, respectively. The blue area represents 95% confidence interval. The x and y axes are on a log-scale; values are shown in natural scale for easier interpretation. CI, confidence interval; Cr, serum creatinine (mg/dL); Cys, serum cystatin C (mg/L); mClcr, measured clearance of creatinine.

Fig. 2.

Association of difference in eGFR–mClcr versus muscle mass. As shown, eGFRcys (left) and eGFRcr (right) were affected in the same direction by the amount of muscle mass–overestimation occurred at lower muscle mass and underestimation at higher muscle mass, though the magnitude of the association was greater for eGFRcr. The median difference of eGFRcys and eGFRcr vs mClcr in patients whose muscle mass was under the median (left side of the black line) was 4.8 and 15.8 mL/min/1.73 m², respectively. In contrast, underestimation occurred in patients whose muscle mass was above the median: the median difference of eGFRcys and eGFRcr vs mClcr was −9.6 and −2.3 mL/min/1.73 m², respectively. The x axis is on log-scale; values are shown in natural scale for easier interpretation. eGFR, estimated glomerular filtration rate; eGFRcr, estimated glomerular filtration rate from creatinine; eGFRcys, estimated glomerular filtration rate from cystatin C; mClcr, measured clearance of creatinine.

Fig. 3.

Survival according to eGFRcys and eGFRcr stratified by muscle mass. After stratifying by muscle mass below the cutoff value for sarcopenia, similar survival was observed in high vs low eGFRcys (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.38–1.42, P = .36), but different survival was observed in low vs high muscle mass (HR 2.8, 95% CI 1.44–5.27, P = .002). Likewise, survival was not different in high vs low eGFRcr (HR 0.92, 95% CI 0.49–1.72, P = .78), while it was in low vs high muscle mass (HR 2.96, 95% CI 1.58–5.56, P = .001). Low muscle represents <20 kg of muscle mass for men or <15 kg for women.(17) Low eGFRcys indicates below the median of eGFRcys (40 mL/min/1.73 m²). Low eGFRcr indicates below the median of eGFRcr (52 mL/min/1.73 m²). eGFR, estimated glomerular filtration rate; eGFRcr, estimated glomerular filtration rate from creatinine; eGFRcys, estimated glomerular filtration rate from cystatin C; Musc, muscle mass.