Hyperhomocysteinemia and Hyperuricemia are Closely Associated with a Decline in Renal Function in Patients with Type 2 Diabetes

Objective: This study examined the association of homocysteine and uric acid with estimated glomerular filtration rate (eGFR) and explored their pathophysiological significance in patients with type 2 diabetes mellitus. Methods: We performed a cross-sectional study in 56 Japanese patients with type 2 diabetes. The correlations of serum total homocysteine level with age, diabetes duration, HbA1c, body mass index, systolic blood pressure, eGFR, urinary albumin-to-creatine ratio (ACR), and uric acid were investigated. The correlation between eGFR and uric acid was also investigated. Serum total homocysteine level was compared in men and women, as well as in patients with and without diabetic nephropathy, hypertension, smoking, and alcohol consumption. Stepwise multiple regression analyses were performed to identify explanatory factors for eGFR, total homocysteine, and uric acid. Results: Serum total homocysteine level showed a significant positive correlation with diabetes duration, ACR, and uric acid, and an inverse correlation with eGFR. Uric acid level and eGFR showed a significant inverse correlation. Patients with diabetic nephropathy and hypertension showed a significantly higher total homocysteine level. Multiple regression analyses demonstrated that age, total homocysteine, and uric acid were independent determinants of eGFR, and that age and eGFR were independent determinants of both total homocysteine and uric acid levels. Conclusion: Although total homocysteine, uric acid, and eGFR showed correlations, the relationship between uric acid and homocysteine might be weaker than that between eGFR and homocysteine, and between eGFR and uric acid. A relatively weak association between hyperuricemia and hyperhomocysteinemia observed in our study suggests confounding by decreased renal function. Both total homocysteine and uric acid can be used as biomarkers of renal dysfunction in patients with type 2 diabetes.