Association Between Glomerular Filtration Rate and Endothelial Function in an Elderly Community Cohort

Background: Endothelial dysfunction is prevalent among individuals with chronic kidney disease. However, the association between glomerular filtration rate and endothelial function in the community is unclear and needs to be investigated in the general population.

Methods: In the community-based Prospective Investigation of the Vasculature of Uppsala Seniors study (PIVUS, n = 952, mean age 70, women 49.3%), we investigated cross-sectional associations between estimated cystatin C-based glomerular filtration rate (eGFR), and 3 measures representing different aspects of endothelial function (endothelial-dependent vasodilation [EDV], endothelial independent vasodilatation [EIDV], and flow-mediated dilatation [FMD]). We also performed pre-specified sub-group analyses in participants with normal eGFR (>60 ml/min/1.73 m(2)).

Results: In the whole cohort, 10 ml/min/1.73 m(2) higher eGFR was associated with 3% higher EDV (p = 0.001) and 2% higher EIDV (p = 0.007), adjusted for age and sex. The associations were attenuated and no longer statistically significant after adjusting for established cardiovascular risk factors. In participants with eGFR >60 ml/min/1.73 m(2), 10 ml higher eGFR was associated with 2% higher EDV (p = 0.04) after adjusting for sex and age. eGFR was not associated to FMD in any model or sub-sample.

Conclusion: This community-based study suggests that eGFR is associated with endothelial function also in persons with normal kidney function, but that this association is largely explained by confounding by established cardiovascular risk factors. Thus, our data do not support the notion of a direct causal interplay between renal and vascular function prior to the development of CKD.