Exceptional parental longevity modifies the associations of kidney function and kidney aging with cardiovascular disease

BACKGROUND: Chronic kidney disease (CKD) is associated with cardiovascular disease (CVD). Exceptional parental longevity protects against CVD. We examined whether exceptional parental longevity modified the associations of kidney function and kidney aging with CVD in older adults. METHODS: We used data from LonGenity (2008-2023), a cohort of Ashkenazi Jewish adults aged 65-95, comparing the offspring of parents with exceptional longevity to the offspring of parents with usual survival. Exceptional longevity was defined as living beyond 95 years. Kidney function was estimated using glomerular filtration rate (eGFR); CKD was defined as eGFR < 60 mL/min/1.73m2. Kidney aging was assessed using kidney age gap-the difference between proteomic kidney age and chronological age. Logistic and Cox regression tested associations between eGFR and kidney aging with prevalent and incident CVD, respectively. Effect modification was tested using interaction terms and stratified analyses. RESULTS: Among 1180 participants (mean age 76 ± 7 years), 23% had CKD; median kidney age gap was -0.04 years (IQR: -0.67, 0.66); 15% had baseline CVD. eGFR and kidney aging were associated with prevalent CVD, but not incident CVD. Exceptional parental longevity did not modify the association of eGFR with prevalent or incident CVD. However, it did modify the association of kidney age gap with incident, but not prevalent, CVD. In the offspring of parents with exceptional longevity, higher kidney age gap was associated with increased incident CVD hazard (HR: 1.90; 95% CI: 1.23, 2.94), but not in the offspring of parents with usual survival (HR: 0.79 95% CI: 0.59, 1.05). CONCLUSIONS: Kidney age gap may reflect early CVD risk in biologically resilient populations, thus warranting prospective studies.