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. Although CKD is a well known risk factor for all-cause or cardiovascular mortality, 1 the clinical consequences of an abnormally high GFR or renal hyperfiltration (RHF) have not been adequately evaluated. On the basis of several cross-sectional studies, RHF is known to be associated with various medical conditions, such as diabetes, 2,3 hypertension, 4 obesity, 5 prehypertension, and prediabetes, 6 as well as lifestyle factors, such as smoking, 7 lack of physical activity, 8 and low aerobic fitness. 9 Although these conditions are well known risk factors for early mortality, 10 the clinical implications of RHF remain unclear.Several cohort studies and meta-analyses have reported a J-shaped association between GFR and all-cause and cardiovascular mortality. However, the increased mortality associated with a higher GFR was commonly regarded as an overestimation of GFR because of muscle wasting in a high-risk group. [11][12][13][14][15][16][17] The disappearance of the J-shaped association between GFR and mortality within a younger age group in the higher GFR range is considered as supporting evidence for the overestimation of the true GFR

Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD

“…This has generally been explained by muscle wasting related to chronic diseases, although a high eGFRcre, possibly a marker of hyperfiltration, was recently associated with mortality, even after adjusting for muscle mass (27). Our findings suggest that other factors associated with chronic diseases, such as increased levels of inflammatory markers and fibrinogen, may bias risk prediction in the same direction as low muscle mass and similarly confound longitudinal studies using eGFR.…”

A predictive model of progressive chronic kidney disease in idiopathic nephrotic syndrome

“…The shaded areas represent 95 % confidence intervals Therefore, our conclusions should only be applied to similar samples. In addition, we were not able to systematically analyze time-dependent variables, such as hypertension, glomerular hyperfiltration, and proteinuria, that might contribute to renal outcome [8,49,50]. Finally, in our study we were only able to estimate survival times.…”

The relationship between estimated glomerular filtration rate trajectory and all-cause mortality in type 2 diabetes: the Fremantle Diabetes Study

“…An alternative explanation is that the highest eGFR category in FDS1 contained a disproportionately large percentage of patients with hyperfiltration and others may have progressed through this phase before recruitment. In both these cases, there is an increased associated risk of progression to diabetic nephropathy (39) and, if independent associations in the general population apply to diabetes, an increased risk of subclinical and overt cardiovascular disease (40,41) and allcause death (5). Support for the latter explanation comes from GBM-defined eGFR trajectories in a large sub-group of FDS1 patients.…”

“…Introduction those with glomerular hyperfiltration (an eGFR ≥125 to ≥140 mL/min/1.73 m 2 by isotopic measurement in various studies) (3) which has a debated but likely association with more rapid progression of diabetic nephropathy (4) and which may also be an independent predictor of mortality in the general population (5). The evidence that eGFR has a U-shaped association with mortality, including diabetes, questions the validity of studies which have assessed the prognostic significance of renal disease in statistical models assuming simple linearity or using categorisation that belies the complexity of the relationship.…”