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

Abstract

Rationale & ObjectiveFemales 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 DesignA population-based cohort study. Setting & Participants1,127,731 adults living in Wales, UK, within the Secure Anonymised Information Linkage Databank. ExposuresSex 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. OutcomesThe yearly declines in eGFR and the risk of incident kidney failure defined as long-term KRT and/or sustained eGFR<15mL/min/1.73m2. Analytical ApproachLinear mixed effects models and Cox proportional hazards analysis. ResultsThe average decline in eGFR age ≤73 was equal in males and females. After age 73, eGFR decline was faster in males than females, particularly for males with heart failure (males -1.22 mL/min/1.73m2 per year: 95% confidence interval (CI) -1.25 to -1.20 versus females -0.87mL/min/1.73m2: CI -0.89 to -0.85) and current smokers (males -1.58 mL/min/1.73m2 per year: CI -1.60 to -1.55 versus females -1.27 mL/min/1.73m2: CI -1.29 to -1.25). Socioeconomic deprivation was one of the most impactful risk factors on eGFR decline among females age >73, 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-value for age<0.001). LimitationsStudy 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. ConclusionseGFR 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. While further work is required to explore less well-recognised risk factors these findings may inform clinical management strategies of CKD overall and within sex-specific groups.