GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts

Abstract

Background: Population mean GFR is lower in older age, but it is unknown whether healthy aging is associated with preserved rather than lower GFR in some individuals.

Methods: We investigated the cross-sectional association between measured GFR, age, and health in persons aged 50-97 years in the general population through a meta-analysis of iohexol clearance measurements in three large European population-based cohorts. We defined a healthy person as having no major chronic disease or risk factors for CKD and all others as unhealthy. We used a generalized additive model to study GFR distribution by age according to health status.

Results: There were 935 (22%) GFR measurements in persons who were healthy and 3274 (78%) in persons who were unhealthy. The mean GFR was lower in older age by -0.72 ml/min per 1.73 m² per year (95% confidence interval [95% CI], -0.96 to -0.48) for men who were healthy versus -1.03 ml/min per 1.73 m² per year (95% CI, -1.25 to -0.80) for men who were unhealthy, and by -0.92 ml/min per 1.73 m² per year (95% CI, -1.14 to -0.70) for women who were healthy versus -1.22 ml/min per 1.73 m² per year (95% CI, -1.43 to -1.02) for women who were unhealthy. For healthy and unhealthy people of both sexes, both the 97.5th and 2.5th GFR percentiles exhibited a negative linear association with age.

Conclusions: Healthy aging is associated with a higher mean GFR compared with unhealthy aging. However, both the mean and 97.5 percentiles of the GFR distribution are lower in older persons who are healthy than in middle-aged persons who are healthy. This suggests that healthy aging is not associated with preserved GFR in old age.

Keywords: epidemiology and outcomes; geriatric nephrology; glomerular filtration rate; glomerular hyperfiltration; renal dysfunction; renal function decline.

Graphical abstract

Figure 1.

Inclusion of participants from RENIS-T6, RENIS-FU, BIS, and AGES-Kidney in the meta-analysis. The dashed arrow from RENIS-T6 to RENIS-FU indicates the repeated measurements of GFR in the RENIS cohort after a mean follow-up of 5.6 years.

Figure 2.

Unadjusted GFR according to cohort and health status. Body surface area–indexed GFR measured as plasma iohexol clearance and plotted against age in the RENIS, BIS, and AGES-Kidney cohorts (n=4209). The marker colors indicate cohort membership. Filled circles indicate measurements in persons who were healthy and crosses in persons who were unhealthy. Measurements for both the baseline (RENIS-T6) and the follow-up examinations (RENIS-FU) of the same persons in the RENIS cohort are shown. The red and green curves represent unadjusted locally estimated scatterplot smoothing fits to measurements in people who were unhealthy and healthy, respectively.

Figure 3.

GFR according to sex and health status. Predicted median (bold black line) and 2.5th and 97.5th percentiles (dashed black lines) as a function of age for healthy women (upper panel) and men (lower panel). The predicted median (gray line) and 95% interpercentile intervals (dark gray band) are shown for persons classified as unhealthy for comparison. The gray dashed line indicates the 60 ml/min per 1.73 m² level.

Figure 4.

Measured and estimated GFR in healthy persons according to sex. Predicted medians (bold lines) and 2.5th and 97.5th percentiles (dashed lines) of iohexol clearance (black) and eGFR based on creatinine (red) as functions of age for healthy women (upper panel) and men (lower panel). The gray dashed line indicates the 60 ml/min per 1.73 m² level.