<b><i>Objective:</i></b><i>APOE </i>gene variants may contribute to the risk of chronic kidney disease. Our aim was to determine whether the common <i>APOE</i>-ε2/ε3/ε4 polymorphism is associated with a reduced estimated glomerular filtration rate (eGFR) in the RENASTUR population, a cohort of elderly individuals from the region Asturias (northern Spain). <b><i>Methods:</i></b> A total of 743 Spanish Caucasians aged 55-85 years were genotyped for the <i>APOE</i>-ε2/ε3/ε4 polymorphism. Individuals with a previous diagnosis of renal disease were not eligible for the study. Participants with a documented history of type 2 diabetes mellitus (T2DM) or hypertension or who were receiving antidiabetic or antihypertensive drugs<b> </b>were classified as diabetics and hypertensives. The eGFR was calculated using the Modification of Diet in Renal Disease formula, and those with an eGFR <60 ml/min/1.73 m² (n = 91) were considered as having impaired renal function. The effect of alleles and genotypes on clinical (hypertension, T2DM) and analytical findings was statistically determined. <b><i>Results:</i></b> In addition to age and T2DM, <i>APOE</i>-ε2 was significantly associated with an eGFR <60 ml/min/1.73 m² (p = 0.002; OR = 2.30). This association remained statistically significant after correction for multiple variables. Although the effect of the <i>APOE</i>-ε2 allele on the eGFR was observed both among diabetics and nondiabetics, the significance was stronger in the T2DM group. <b><i>Conclusion:</i></b> The <i>APOE</i>-ε2 allele is a genetic risk factor for impaired renal function among healthy elderly Spanish individuals.