415-P: Different Diabetic Kidney Disease (DKD) Phenotypes and Urinary Fetuin-A Levels in Subjects with Type 2 Diabetes
Authors: GAROFOLO MONIA , LUCCHESI DANIELA , GIAMBALVO MASSIMO , CAPOBIANCO MARTINA , MANCINI GABRIELE , DEL PRATO STEFANO , MARCHETTI PIERO , PENNO GIUSEPPE 
Published: June 2024

Introduction & Objective: The hepatokine fetuin-A is associated with insulin resistance and promotes inflammation in T2D, contributing to the development of DKD. In this observational, single-center study, we evaluated the potential of this novel urinary biomarker in differentiating DKD phenotypes in T2D subjects.
Methods: DKD phenotypes were defined based on increased albuminuria (uACR &gt;30 mg/g) and/or reduced CKD-EPI eGFR (&lt;60 ml/min/1.73 m2). Urinary excretion of fetuin-A was measured (DNLite-IVD103 ELISA, IBL International GmbH, Hamburg) in first-morning urine samples and corrected for urinary creatinine levels (ng/mg Cr, uFCR).
Results: Among 256 subjects, 26.2% had No-DKD, 24.6% increased uACR only (Alb+), 24.2% non-albuminuric DKD (Alb-DKD) and 25.0% albuminuric DKD (Alb+DKD). uFCR correlated with uACR (r=0.529, p&lt;0.0001) and inversely with eGFR (r=-0.266, p&lt;0.0001). uFCR levels differed among phenotypes (p&lt;0.0001): No-DKD 6.80 (IQR 3.01-15.16; ref), Alb+ 13.37 (5.02-40.04, p=0.003), Alb-DKD 7.02 (3.37-19.40, p=0.865) and Alb+DKD 47.40 (13.83-123.06, p&lt;0.0001). By logistic regression, ln-uFCR was an independent covariate of uACR ≥30 mg/g (OR 1.84, 95%CI 1.49-2.26, p&lt;0.0001) irrespective of age, sex, DD, BMI, HbA1c, hypertension, dyslipidemia, RAS-blockers and eGFR. Consistently, ln-uFCR was associated to eGFR &lt;60 ml/min/1.73 m2 (OR 1.34, 95%CI 1.28-1.61, p=0.001) after adjustment for the same covariates and uACR instead of eGFR. After adjustment (No-DKD ref), ln-uFCR was an independent covariate of Alb+ (OR 1.38, 95%CI 1.03-1.86, p=0.029) and Alb+DKD (2.97, 1.91-4.64, p&lt;0.0001), but not of Alb-DKD (p=0.433). Finally, Alb+ (OR 2.14, p=0.054) and Alb+DKD (6.42, p&lt;0.0001), but not Alb-DKD (p=0.863), were independent covariates of uFCR levels above median.
Conclusion: uFCR levels might provide an innovative diagnostic tool to improve characterization of DKD phenotypes in T2D, being independently associated with the albuminuric state.

Disclosure
M. Garofolo: Consultant; Novo Nordisk, Eli Lilly and Company, Merck Sharp & Dohme Corp., Bayer Inc. D. Lucchesi: None. M. Giambalvo: None. M. Capobianco: None. G. Mancini: None. S. Del Prato: Advisory Panel; Abbott. Speaker's Bureau; Abbott. Advisory Panel; Amarin Corporation, Applied Therapeutics Inc. Speaker's Bureau; Boehringer-Ingelheim, Berlin-Chemie AG, Boehringer-Ingelheim. Advisory Panel; Eva Pharma. Speaker's Bureau; Eva Pharma, Merck Sharp & Dohme Corp. Advisory Panel; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Advisory Panel; Sanofi, Sun Pharmaceutical Industries Ltd., Menarini International. Speaker's Bureau; Menarini International, Laboratori Guidotti. P. Marchetti: Speaker's Bureau; Eli Lilly and Company, Novo Nordisk. G. Penno: Advisory Panel; Eli Lilly and Company, Bayer Inc. Consultant; Novo Nordisk, AstraZeneca, Boehringer-Ingelheim.

Funding
Ministero Italiano dell'Universita e della Ricerca, Progetti di Rilevante Interesse Nazionale (PRIN) 2020 - Cod. 2020SH2ZZA