Sex Differences in Age-Related Loss of Kidney Function

CKD is more prevalent in women, but more men receive kidney replacement therapy for kidney failure. This apparent contradiction is not well understood.

We investigated sex differences in the loss of kidney function and whether any sex disparities could be explained by comorbidity or CKD risk factors. In the Renal Iohexol Clearance Survey (RENIS) in northern Europe, we recruited 1837 persons (53% women, aged 50-62 years) representative of the general population and without self-reported diabetes, CKD, or cardiovascular disease. Participants' GFR was measured by plasma iohexol clearance in 2007-2009 (n=1627), 2013-2015 (n=1324), and 2018-2020 (n=1384). At each study visit, healthy persons were defined as having no major chronic diseases or risk factors for CKD. We used generalized additive mixed models to assess age- and sex-specific GFR decline rates.

Women had a lower GFR than men at baseline (mean [SD], 90.0 [14.0] versus 98.0 [13.7] ml/min per 1.73 m²; P<0.001). The mean GFR change rate was -0.96 (95% confidence interval [CI], -0.88 to -1.04) ml/min per 1.73 m² per year in women and -1.20 (95% confidence interval [CI], -1.12 to -1.28) in men. Although the relationship between age and GFR was very close to linear in women, it was curvilinear in men, with steeper GFR slopes at older ages (nonlinear effect; P<0.001). Healthy persons had a slower GFR decline, but health status did not explain the sex difference in the GFR decline.

Among middle-aged and elderly individuals in the general population, decline in the mean GFR in women was slower than in men, independent of health status.