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

Ming-Tsun Tsai; Wei-Cheng Tseng; Kuo-Hua Lee; Chih-Ching Lin; Shuo-Ming Ou; Szu-Yuan Li

doi:10.1093/ckj/sfae065

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

Clin Kidney J. 2024 Mar 14;17(4):sfae065. doi: 10.1093/ckj/sfae065. eCollection 2024 Apr.

Authors

Ming-Tsun Tsai^{1

2

3}, Wei-Cheng Tseng^{1

2

3}, Kuo-Hua Lee^{1

2

3}, Chih-Ching Lin^{1

2

3}, Shuo-Ming Ou^{1

2

3}, Szu-Yuan Li^{1

2

3}

Affiliations

¹ Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
² School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

Background: 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.

Methods: 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.

Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (r_s = 0.67, P < .001) and a negative correlation with eGFR (r_s = -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.

Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

Keywords: biomarker; biopsy-proven kidney diseases; fetuin-A; histopathology; major adverse kidney events.