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A population-based study investigating gender differences in kidney function found that women had lower function at baseline, but that men's function declined faster, especially at older ages. The results suggest the need for age- and sex-adjusted definitions of kidney disease, the researchers said.

Among 1,837 people ages 50-62, who were representative of the general population, the mean glomerular filtration rates (GFR) at baseline were 90 and 98 mL/min/1.73 m² for women and men, respectively (P<0.001). But additional measurements over a follow-up of approximately 11 years showed that men had a 25% steeper mean GFR decline than women (-1.20 vs -0.96, P <0.0001), reported Toralf Melsom, MD, PhD, of the University Hospital of North Norway in Tromsø, and colleagues.

As shown in their study in the , the relationship between age and GFR was approximately linear in women, but curvilinear in men, with steeper GFR slopes at older ages (nonlinear effect, P<0.001). Healthy individuals had a slower GFR decline, but health status did not explain the gender difference in loss of kidney function, the researchers said.

"This is the first study that repeats accurate measurements of kidney function in relatively healthy women and men during aging," Melsom said in a statement. "By doing so we provide important knowledge regarding age-related loss of kidney function and sex disparities in the prevalence of chronic kidney disease (CKD). The study may in part explain why more women are diagnosed with early CKD and more men develop severe CKD and kidney failure during aging."

Accurate measurements were a key aspect of the study, Melsom added. His team assessed kidney function with intravenous injection of the contrast media iohexol, a kidney filtration marker. Three to four hours after the injection, the researchers collected blood samples to calculate the kidney filtration rate.

"This method has been regarded as too complicated to use in population-based studies; however during 11 years of follow-up, we performed more than 4,000 kidney function measurements in 1,837 people," Melsom said.

The findings could support age- and sex-specific cutoff values for defining CKD, the researchers said. For example, a healthy 70-year-old woman with a GFR of 59 mL/min/1.73 m² and no albuminuria is currently labeled as having CKD stage 3a, even though her GFR is within the 95% age-and sex-specific reference range in European populations.

"A CKD diagnosis may cause anxiety and referral to a specialist health care center, but according to our study her risk of accelerated GFR loss is low, and the risk of end stage kidney disease has been found to be minimal," the researchers wrote.

Conversely, a GFR of 65 mL/min/1.73 m² in a man younger than 50 does not fulfill the CKD criteria, although his GFR is clearly abnormal, and his lifetime risk of progression to CKD stages 4 and 5 may be significant, the team explained. "Studies on measured GFR that include sex-specific morbidity or mortality endpoints are needed to decide whether the CKD definition should be adjusted for age and sex."

Individuals in the current study came from the Renal Iohexol Clearance Survey (RENIS), the only general population cohort with repeated measurement of GFR. Approximately half the participants (53%) were women, and healthy persons in the study had no major chronic diseases or risk factors for CKD.

The researchers measured GFR by plasma iohexol clearance in 2007-2009, 2013-2015, and 2018-2020 and used generalized additive mixed statistical models to assess age- and sex-specific GFR decline rates.

Study limitations, the team said, included that participants were all of European ancestry, which could limit the generalizability of the findings, and that although a stringent definition of "healthy" was used, it was not possible to exclude the possibility that some mechanisms contributing to GFR decline in participants defined as healthy could have been pathological rather than age-related.

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