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  • Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Clinical kidney journal (2024-04-05)
Ming-Tsun Tsai, Wei-Cheng Tseng, Kuo-Hua Lee, Chih-Ching Lin, Shuo-Ming Ou, Szu-Yuan Li
ABSTRACT

Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Anti-AHSG antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-LRP2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution