Method of glomerular filtration rate estimation affects prediction of mortality risk

Abstract

Decreased kidney function, determined using a serum creatinine-based estimation of GFR, is associated with a higher risk for mortality from cardiovascular disease. Equations incorporating cystatin C improve the estimation of GFR, but whether this improves the prediction of risk for mortality is unknown. We measured cystatin C on 6942 adult participants in the Third National Health and Nutrition Examination Survey Linked Mortality File, including all participants who had high serum creatinine (>1.2 mg/dl for men; >1.0 mg/dl for women) or were older than 60 yr and 25% random sample of participants who were younger than 60 yr. We estimated GFR using equations that included standardized serum creatinine, cystatin C, or both. Participant data were linked to the National Death Index. A total of 1573 (22.7%) deaths (713 deaths from cardiovascular disease) occurred during a median of 8 yr. Lower estimated GFR based on cystatin C was strongly associated with higher risk for overall and cardiovascular mortality across the range of normal to moderately decreased estimated GFR. Creatinine-based estimates of GFR resulted in weaker associations, with the association between estimated GFR and all-cause mortality reversed at higher levels of estimated GFR. An equation using both creatinine and cystatin C (in addition to age, race, and gender) resulted in weaker associations than equations using only cystatin C (with or without age, race, and gender). In conclusion, despite better performance in terms of estimating GFR, equations based on both cystatin C and creatinine do not predict mortality as well as equations based on cystatin C alone.

Figure 1.

(A and B) Receiver operating characteristics for all-cause (A) and cardiovascular (B) mortality for three GFR estimating equations. ▵, 60 ml/min per 1.73 m²; □, 75 ml/min per 1.73 m²; ♢, 90 ml/min per 1.73 m². All P < 0.001 versus eGFRcreat.

Figure 2.

(A and B) Adjusted annual rate, by eGFR of all-cause mortality (A) and cardiovascular mortality (B). Incidence rates were adjusted to the incidence rate of a white woman with the lowest risk category for categorical covariates (smoking status, diabetes status, previous CVD, CRP category, and BP category) and the overall mean values of continuous covariates (age, body mass index, LDL and HDL cholesterol, and log triglycerides). Vertical bars represent histogram of the mean of all three eGFRs.