Serum Pentosidine Levels Are Associated with Early Declines in Estimated Glomerular Filtration Rate, Independent of Glycemic Status: A Cross-Sectional Analysis from the Fukuoka Epidemiological Study of Atherosclerosis

Background Advanced glycation end products, particularly pentosidine, are implicated in age-related diseases and are influenced by renal function and glycemic status. Although elevated pentosidine levels are well documented in individuals with advanced reductions in renal function, their association with early declines in estimated glomerular filtration rate (eGFR), including ranges not meeting diagnostic criteria for chronic kidney disease (CKD), remains unclear. Methods We conducted a cross-sectional analysis of 813 Japanese adults from the Fukuoka Epidemiological Study of Atherosclerosis who underwent routine health checkups. Serum pentosidine and Nε-(carboxymethyl)lysine (CML) levels were measured and analyzed in relation to eGFR categories and glycemic markers. Results Serum pentosidine levels were significantly associated with early declines in eGFR, even among individuals with eGFR values within ranges not meeting CKD diagnostic criteria (P for trend < 0.01), whereas serum CML levels remained largely unchanged. In multivariable logistic regression analysis, lower eGFR category was independently associated with elevated serum pentosidine levels (odds ratio, 1.95; 95% confidence interval, 1.40–2.70) after adjustment for glycated hemoglobin levels. In contrast, glycemic status was not significantly associated with serum pentosidine levels. Metabolic and inflammatory markers were inversely associated with serum pentosidine levels. Conclusions Early declines in eGFR, even within ranges not meeting CKD diagnostic criteria, were independently associated with higher serum pentosidine levels, irrespective of glycemic status in this general population. These findings suggest that subtle reductions in renal function are associated with alterations in serum pentosidine levels, potentially reflecting cumulative oxidative stress and renal handling beyond glycemic exposure.