Combined association of albuminuria and cystatin C-based estimated GFR with mortality, coronary heart disease, and heart failure outcomes: the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Background: Serum cystatin C level has been shown to have a stronger association with clinical outcomes than serum creatinine level. However, little is known about the combined association of cystatin C-based estimated glomerular filtration rate (eGFR(cys)) and albuminuria with clinical outcomes, particularly at levels lower than current chronic kidney disease (CKD) cutoffs.

Study design: Prospective cohort.

Setting & participants: 10,403 ARIC (Atherosclerosis Risk in Communities) Study participants followed up for a median of 10.2 years.

Predictor: eGFR(cys), albuminuria.

Outcomes: Mortality, coronary heart disease (CHD), and heart failure, as well as a composite of any of these separate outcomes.

Results: Both decreased eGFR(cys) and albuminuria were associated independently with the composite outcome, as well as mortality, CHD, and heart failure. Although eGFR(cys) of 75-89 mL/min/1.73 m(2) in the absence of albuminuria (albumin-creatinine ratio [ACR] <10 mg/g) or albuminuria with ACR of 10-29 mg/g with normal eGFR(cys) (90-104 mL/min/1.73 m(2)) was not associated significantly with any outcome compared with eGFR(cys) of 90-104 mL/min/1.73 m(2) and ACR <10 mg/g, the risk of each outcome was significantly higher in those with both eGFR(cys) of 75-89 mL/min/1.73 m(2) and ACR of 10-29 mg/g (for mortality, HR of 1.4 [95% CI, 1.1-2.0]; for CHD, HR of 1.9 [95% CI, 1.4-2.6]; for heart failure, HR of 1.8 [95% CI, 1.2-2.7]). Combining the 2 markers improved risk classification for all outcomes (P < 0.001), even in those without overt CKD.

Limitations: Only one measurement of cystatin C.

Conclusions: Mildly decreased eGFR(cys) and mild albuminuria independently contributed to the risk of mortality, CHD, and heart failure. Even minimally decreased eGFR(cys) (75-89 mL/min/1.73 m(2)) is associated with increased risk in the presence of mild albuminuria. Combining the 2 markers is useful for improved risk stratification even in those without clinical CKD.

Figure 1

Hazard ratios with 95% confidence intervals of estimated glomerular filtration rate (eGFR) with the composite outcome (top row of panels), all-cause mortality (second row), coronary heart disease (third row), and heart failure (bottom row). Graphs include the interaction between eGFR and log-ACR (albumin-creatinine ratio). eGFR knots at 45, 60, 75, 90, and 105 mL/min/1.73 m². Reference group is eGFR of 95 mL/min/1.73 m² and ACR of 5 mg/g.