BackgroundHyperhomocysteinemia has been linked with chronic kidney disease (CKD). The present study investigated whether homocysteine (Hcy) serum levels might serve as a marker for the advancement of diabetic nephropathy (DN).MethodsClinical and laboratory indicators including Hcy, vitamin D (VD), urine protein, estimated glomerular filtration rate (eGFR) and the urinary protein/creatinine ratio in subjects > 65 years with DN (n = 1,845), prediabetes (n = 1,180) and in a non-diabetes (control) group (n = 28,720) were analyzed.ResultsDN patients had elevated Hcy concentrations, decreased VD and higher urinary protein levels, a reduced eGFR and a higher urinary protein/creatinine ratio compared with prediabetic and control subjects. After correcting for urinary protein quantitation, multivariate analysis revealed that both the Hcy concentration (P< 0.010) and urinary protein/creatinine ratio (P< 0.001) were risk factors, while the VD2 + VD3 serum concentration (P< 0.001) was a protective factor for DN. Moreover, Hcy > 12 µmol/L was a cut-off value for predicting advanced DN.ConclusionHcy serum concentration is a potential marker for the advancement of CKD in DN but not prediabetes patients.