Sex and the Relationship Between Cardiometabolic Risk Factors and Estimated GFR Decline: A Population-Based Cohort Study

Abstract

Rationale & Objective

Females have a higher prevalence of chronic kidney disease (CKD) than males but are less likely to be treated with kidney replacement therapy (KRT). We studied the interaction between sex and the association of cardiometabolic risk factors for the decline in kidney function over time.

Study Design

A population-based cohort study.

Setting & Participants

1,127,731 adults living in Wales, United Kingdom, within the Secure Anonymised Information Linkage Databank.

Exposure

Sex and risk factors including age, estimated glomerular filtration rate (eGFR), cardiometabolic conditions, smoking, and socioeconomic deprivation. These risk factors were defined using primary care records.

Outcome

The yearly declines in eGFR and the risk of incident kidney failure defined as long-term KRT and/or sustained eGFR < 15 mL/min/1.73 m².

Analytical Approach

Linear mixed effects models and Cox proportional hazards analysis.

Results

The average decline in eGFR at age ≤73 years was equal in males and females. After age 73 years, eGFR decline was faster in males than females, particularly for males with heart failure (males −1.22 mL/min/1.73 m² per year [95% CI, −1.25 to −1.20] vs females −0.87 mL/min/1.73 m² per year [95% CI, −0.89 to −0.85]) and current smokers (males −1.58 mL/min/1.73 m² per year [95% CI, −1.60 to −1.55] vs females −1.27 mL/min/1.73 m² per year [95% CI, −1.29 to −1.25]). Socioeconomic deprivation was one of the most impactful risk factors on eGFR decline among females aged >73 years, whereas cardiometabolic risk factors were more important among males. Older females at baseline were less likely to develop incident kidney failure than older males (P for age < 0.001).

Limitations

Study of people who were almost exclusively White and who had blood laboratory test data. Reliance on creatinine-based eGFR. Albuminuria and body mass index data were incomplete.

Conclusions

The eGFR decline was faster in males than in females, especially in the setting of heart failure and smoking. Socioeconomic deprivation was an important risk factor associated with eGFR decline, particularly for females. further work is required to explore less well-recognized risk factors, but these findings may inform clinical management strategies of CKD overall and within sex-specific groups.

Plain-Language Summary

Kidney function is known to decline at a faster rate among males than females. This study incorporated blood laboratory test results from the routine care of 1.1 million adults living in the United Kingdom and found that the decline in kidney function associated with risk factors varied by sex. Before and at the age of 73 years, the decline in kidney function was similar between males and females. After age 73, cardiometabolic risk factors were associated with faster decline in kidney function among males than females, specifically heart failure and smoking. Socioeconomic deprivation was also associated with the decline in kidney function for both sexes, but it was a stronger risk factor among females. These findings may inform the management of kidney disease overall and within sex-specific groups.