AIMS: To investigate the association of soluble CD14 (sCD14) with diabetic kidney disease (DKD) and its prediction performance for kidney function staging. METHODS: A cross-sectional study of 80 type 2 diabetes (T2D) patients was conducted. Each participant was screened for DKD, and the diagnostic criterion for DKD was a glomerular filtration rate (eGFR) <
60 mL/min/1.73m RESULTS: sCD14 was higher in DKD patients than in T2D patients without kidney disease (p <
0.002). sCD14 was progressively higher in DKD patients according to the kidney function stage (p <
0.002). Also, sCD14 was higher in DKD patients in hemodialysis than those who did not receive renal replacement therapy (p <
0.002). In DKD patients, sCD14 was positively correlated with creatinine (r = 0.282, p = 0.042) and negatively correlated with eGFR (r = -0.365, p = 0.007). The levels of sCD14 were predictive of G3 (AUC = 0.822), G4 (AUC = 0.876), and G5 (AUC = 0.924) stages of kidney function. In a multivariate logistic regression model adjusted for age, sex, and diabetes duration, sCD14 ≥ 1720 ng/mL were associated with G3 stage (OR = 8.92, p = 0.023), G4 (OR = 7.92, p = 0.011) and G5 stage (OR = 18.47, p = 0.017) in DKD patients. CONCLUSION: Circulating levels of sCD14 are associated with DKD and perform well for kidney function staging. Thus, it is a good candidate for assessing the risk of kidney disease progression.