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Urinary fetuin-A peptides a potential biomarker for renal dysfunction in diabetics

Clinical Kidney Journal
Reuters Health - 05/11/2020 - In patients with type 2 diabetes, urinary fetuin-A peptides was associated with impaired kidney function before albuminuria appeared, in a proteome data analysis.

"Fetuin-A peptides had a significant added value to albuminuria, the currently used method to detect impaired kidney function," Dr. Petra Zuerbig of Mosaiques Diagnostics GmbH in Hannover, Germany, told Reuters Health by email. "The findings confirmed the use of CKD273, a proteomic-based classifier, which also includes fetuin-A peptides. This test is well established and was already used in a clinical trial for the early detection of diabetic kidney disease." (https://bit.ly/34Z7PyA)

As reported in the Clinical Kidney Journal, Dr. Zuerbig and colleagues analyzed urinary peptides from 1,491 diabetic patients with (647) and without (844) kidney disease. Those with diabetic kidney disease (DKD) had a mean age of 64; mean eGFR of 49.36 mL/min/1.73(2); and urinary albumin excretion (UAE) of 370.38 mcg/min.

By contrast, those without DKD had a mean age of 59; eGFR of 75.71 mL/min/1.73(2); and UAE of 21.16 mcg/min.

The researchers identified 14 different urinary protein fragments belonging to the region of the connecting peptide (amino acid 301-339) of the fetuin-A protein.

Calpains (CAPN1 and CAPN2), matrix metalloproteinase and pepsin A-3 were identified as potential proteases that were partially confirmed by previous in vitro studies.

Combined fetuin-A peptides (mean of amplitudes) were significantly increased in type 2 diabetes patients with kidney disease.

Further, fetuin-A peptide levels displayed a significant negative correlation with baseline eGFR values (r= -0.316)) and with the slope (%) of eGFR per year (r= -0.096).

A multiple regression model including fetuin-A peptide and albuminuria resulted in a significantly improved correlation with eGFR (r= -0.354) compared with albuminuria, indicating that fetuin-A provided added value.

Dr. Zuerbig said, "Currently, we are refining another (urinary proteome) test for COVID-19-infected patients. This test differentiates between moderate/severe and critical/fatal disease outcomes."

Dr. Jason Ng, Clinical Unit Leader for Diabetes, Division of Endocrinology at Metabolism at UPMC in Pittsburgh called the findings "promising" in an email to Reuters Health.

"The study shows associations and the study design is solid," he said, "but the exact role of fetuin A in the pathology of diabetes and insulin resistance is still being determined, so more work is needed to explore how fetuin A can be used as a marker, what are the thresholds, what values are clinically meaningful, cutoff points which show definitive kidney disease progression, etc.

"Clinically relevant data are needed to outline how clinicians would use the fetuin A to impact patient care, what therapies could we use to improve kidney disease outcomes associated with diabetes, what values would make us worried about kidney disease progression, etc.," he said. "Much more work needs to be done to fully explore these associations to be clinically useful."

The proteome analysis was conducted by Mosaiques Diagnostics. Two coauthors are employees of the company and one is a cofounder and shareholder.

By Marilynn Larkin

SOURCE: https://bit.ly/3eyGNl4 Clinical Kidney Journal, online October 23, 2020.

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