770 Urinary PTM3 Fetuin-A in CKD patients with and without diabetic kidney disease

• Published in: Nephrology, dialysis, transplantation Vol. 39; no. Supplement_1
• Main Authors: Musolino, Michela, D'agostino, Mario, Tripodi, Loredana, Zicarelli, Mariateresa, Cianfrone, Paola, Andreucci, Michele, Coppolino, Giuseppe, Bolignano, Davide
• Format: Journal Article
• Language: English
• Published: 23-05-2024
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfae069.1074

Abstract
Background and Aims
Fetuin-A is a member of the cystatins superfamily, primarily synthesized in the liver, which is involved in multiple physiological processes including calcium homeostasis, cell signaling, calcification inhibition and the regulation of insulin sensitivity. Diabetes mellitus may impact upon Fetuin-A regulation and kidney tubular cells produce Fetuin-A as part of stress and inflammatory response and release it in urine in case of kidney damage.
A novel post-translational modification (PTM) fragment derived from the cleavage of Fetuin-A (PTM3) has recently emerged as a very sensitive biomarker for early kidney damage, but its usefulness in the context of CKD has not been assessed yet. In this study, we aimed at evaluating the clinical significance of urinary PTM3 fetuin A in a pilot cohort of CKD patients with or without diabetic kidney disease (DKD).
Method
We enrolled 47 adult patients with CKD (mean CKD-Epi 40.10 ± 16.5 mL/min/1.73 m2) due to DKD (n = 34) or other causes (n = 13). PTM3 levels were measured in the urine (uPTM3) using a commercially available ELISA kit. 15 healthy individuals served as controls. Clinical, anthropometric and laboratory parameters were also recorded.
Results
Collectively, all CKD patients displayed higher levels of uPTM3 than the ones of control group (0.84 [0.10-1.15] vs 29.68 [2.50-55.16] ng/mL p = 0.0005).
Moreover, uPTM3 values were higher in DKD patients than in non-DKD CKD patients (39.4 [4.20-28.2] vs. 4.15 [0.29-1.38] p < 0.01).
uPTM3 had a remarkable diagnostic capacity at ROC analysis to discriminate CKD patients from controls (AUC 0.776; p < 0.001; Fig. 1) and, within CKD patients, to discriminate between DKD and non-DKD patients (AUC 0.673; p = 0.02; Fig. 2). At multivariate correlation analyses, only proteinuria (β = 0.442; p = 0.02) and BMI (β = 0.334; p = 0.04) values remained significantly associated with uPTM3 Fetuin-A in the whole cohort, thus indicating that renal damage following metabolic syndrome may play a significant impact on the overall balance of this protein.
Conclusion
uPTM3 could be a novel sensitive biomarker reflecting renal damage in CKD patients and could also represent an additional tool for assessing the renal involvement in diabetic patients.
Further studies are needed to evaluate whether uPTM3 measurement may predict different disease evolution in these patients.