Renal hyperfiltration as a novel marker of all-cause mortality

Abstract

Although renal hyperfiltration (RHF) or an abnormal increase in GFR has been associated with many lifestyles and clinical conditions, including diabetes, its clinical consequence is not clear. RHF is frequently considered to be the result of overestimating true GFR in subjects with muscle wasting. To evaluate the association between RHF and mortality, 43,503 adult Koreans who underwent voluntary health screening at Seoul National University Hospital between March of 1995 and May of 2006 with baseline GFR≥60 ml/min per 1.73 m(2) were followed up for mortality until December 31, 2012. GFR was estimated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and RHF was defined as GFR>95th percentile after adjustment for age, sex, muscle mass, and history of diabetes and/or hypertension medication. Muscle mass was measured with bioimpedance analysis at baseline. During the median follow-up of 12.4 years, 1743 deaths occurred. The odds ratio of RHF in participants with the highest quartile of muscle mass was 1.31 (95% confidence interval [95% CI], 1.11 to 1.54) compared with the lowest quartile after adjusting for confounding factors, including body mass index. The hazard ratio of all-cause mortality for RHF was 1.37 (95% CI, 1.11 to 1.70) by Cox proportional hazards model with adjustment for known risk factors, including smoking. These data suggest RHF may be associated with increased all-cause mortality in an apparently healthy population. The possibility of RHF as a novel marker of all-cause mortality should be confirmed.

Keywords: CKD; GFR; epidemiology and outcomes; glomerular hyperfiltration; mortality.

Figure 1.

Association of high eGFR with increased all-cause mortality. The age-, sex-, muscle mass-, and history of diabetes and hypertension medication-adjusted percentile rank of eGFR was associated with higher all-cause mortality after adjustment for age, sex, smoking, regular exercise, regular alcohol ingestion, previous history of diabetes and/or hypertension, BMI, systolic BP, FSG, serum triglyceride, serum HDL-cholesterol, and albuminuria. An additive multivariate Cox regression model was used to compute pointwise estimates and CIs of HR curves of the residuals of eGFR. Penalized splines were used as the smoothing technique, and degrees of freedom of splines were selected on the basis of the lowest Akaike Information Criteria. The solid line represents the aHR, and the dashed lines are 95% CIs.

Figure 2.

Association between RHF and increased all-cause mortality. The Cox proportional hazards model was adjusted for age, sex, smoking, regular exercise, regular alcohol ingestion, previous history of diabetes and/or hypertension, BMI, systolic BP, FSG, serum triglyceride, serum HDL-cholesterol, and albuminuria. The vertical line represents 12 months after health screening. The definition of RHF is given in Concise Methods.