Serum Homocysteine (Hcy), Cystatin C (Cys-C), and Urine Microalbumin (mAlb) are critical for early diagnosis of diabetic nephropathy.

OBJECTIVES

To evaluate the clinical value of combined serum homocysteine (Hcy), cystatin C (Cys-C), and urine microalbumin (mAlb) in early diagnosis of diabetic kidney disease (DKD).

METHODS

A total of 450 participants were retrospectively enrolled, including 150 DKD patients, 150 patients with type 2 diabetes mellitus (T2DM) without nephropathy, and 150 healthy controls. Serum Hcy, Cys-C, HbA1c, glucose, lipids, and urine mAlb were measured. Group differences were assessed using Kruskal-Wallis tests. Receiver operating characteristic (ROC) curves were generated to evaluate diagnostic performance. Least absolute shrinkage and selection operator (LASSO) regression and SHAP analysis were applied to identify key predictive features.

RESULTS

DKD patients showed significantly higher Hcy (22.42±5.15 μmol/L), Cys-C (1.82±0.41 mg/L), and urine mAlb (180.41±42.81 mg/L) than T2DM patients (all P < 0.05). Combined indicators achieved a sensitivity of 82.0%, specificity of 86.7%, and an area under the ROC curve (AUC) of 0.928, outperforming single markers (P < 0.001). LASSO-SHAP analysis identified mAlb dynamics (e.g., AUC, 24-month values) as the dominant predictor.

CONCLUSIONS

Combined Hcy, Cys-C, and mAlb testing improves early DKD diagnostic accuracy, enabling timely intervention. Single-center design and small sample size warrant multicenter validation.