Published in

Karger Publishers, American Journal of Nephrology, p. 1-10, 2023

DOI: 10.1159/000534829

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Urinary Post-Translationally Modified Fetuin-A Protein Is Associated with Increased Risk of Graft Failure in Kidney Transplant Recipients

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

<b><i>Introduction:</i></b> Urinary fetuin-A has been identified as a biomarker for acute kidney injury and is proposed as a biomarker for early detection of kidney function decline. We investigated whether fetuin-A could serve as a marker of graft failure in kidney transplant recipients (KTRs). <b><i>Methods:</i></b> Data of KTR with a functioning graft ≥1 year that were enrolled in the TransplantLines Food and Nutrition Biobank and cohort study were used. Graft failure was defined as the need for re-transplantation or (re-)initiation of dialysis. Urinary fetuin-A was measured using an enzyme-linked immunosorbent assay kit that detected post-translationally modified fetuin-A in the urine (uPTM-FetA). In the main analyses, 24h uPTM-FetA excretion was used. In the sensitivity analyses, we excluded the outliers in 24h uPTM-FetA excretion, and we used uPTM-FetA concentration and uPTM-FetA concentration indexed for creatinine instead of 24h uPTM-FetA excretion. <b><i>Results:</i></b> A total of 627 KTRs (age 53 ± 13 years, 42% females) were included at 5.3 (1.9–12.2) years after transplantation. The estimated glomerular filtration rate (eGFR) was 52 ± 20 mL/min/1.73 m<sup>2</sup> and uPTM-FetA excretion was 34 (17–74) µg/24 h. During a median follow-up of 5.3 (4.5–6.0) years after baseline measurements, 73 (12%) KTRs developed graft failure. The association of 24h uPTM-FetA excretion with increased risk of graft failure was not constant over time, with increased risk only observed after 3 years from baseline measurements, independent of potential confounders including kidney function and 24 h urinary protein excretion (hazard ratio per doubling of 24h uPTM-FetA excretion = 1.31; 95% confidence interval = 1.06–1.61). This finding was robust in the sensitivity analyses. <b><i>Conclusions:</i></b> Our findings suggest that uPTM-FetA can be used as a marker for early detection of graft failure in KTR. Further studies are needed to confirm our findings.