Association of urinary post-translationally modified fetuin-A fragments with diabetic kidney disease risk stratification in Japanese patients with type 2 diabetes
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by Toshiko Mori, Hiroyuki Ito, Taiki Kozasa, Chizuko Yukawa, Suzuko Matsumoto, Hideyuki Inoue, Shinichi Antoku Aims Conventional biomarkers such as estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) primarily reflect glomerular damage and often fail to detect early…
by Toshiko Mori, Hiroyuki Ito, Taiki Kozasa, Chizuko Yukawa, Suzuko Matsumoto, Hideyuki Inoue, Shinichi Antoku
Aims Conventional biomarkers such as estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) primarily reflect glomerular damage and often fail to detect early tubular injury. Consequently, patients with “non-albuminuric diabetic kidney disease (DKD)” may be overlooked. This study evaluated the independent association between urinary post-translationally modified fetuin-A fragments (uPTM-FetA) and DKD risk stratification in Japanese patients with type 2 diabetes.
Methods We conducted a cross-sectional study of 219 outpatients with type 2 diabetes between November 2023 and February 2024 at Edogawa Hospital. First-morning urine samples were analyzed for uPTM-FetA and urinary liver-type fatty acid-binding protein (uL-FABP) using enzyme-linked immunosorbent assays. DKD risk was classified into four categories based on the KDIGO guidelines. The association between uPTM-FetA and higher DKD-risk (categories 2 + 3 + 4) was assessed using multiple logistic regression and restricted cubic spline (RCS) analyses, validated by bootstrapping.
Results The optimal cutoff value for uPTM-FetA was determined to be 11.76 ng/mgCr. Multivariable analysis adjusted for potential confounders revealed that high uPTM-FetA levels were significantly and independently associated with DKD-risk categories 2 + 3 + 4 (adjusted odds ratio: 3.88; 95% CI: 2.02, 7.45; P uPTM-FetA is independently associated with DKD severity and is elevated in a substantial proportion of patients with early-stage disease where conventional markers remain normal. Unlike uL-FABP, which increases predominantly in advanced stages, uPTM-FetA appears to identify tubular stress earlier. Thus, uPTM-FetA serves as a valuable complementary biomarker to uACR for refining DKD risk stratification.