RESUMEN
AIMS: We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM). METHODS: 824 T2DM patients (onsetâ¯≤â¯40â¯years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3â¯ml/min/1.73â¯m2 or >40â¯% from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays. RESULTS: Over 5.7â¯years of follow-up, 25.2â¯% of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95â¯%CI 1.44-2.34, pâ¯<â¯0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8â¯%) and albuminuria (10â¯%). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95â¯%CI 0.68-0.76) to 0.74 (95â¯%CI 0.70-0.78), pâ¯=â¯0.099. CONCLUSIONS: Among seven major candidate proteins, pTNF-R1 partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.