Urinary transforming growth factor-beta-induced gene-h3 (betaig-h3) as a sensitive predictor in chronic cyclosporine

C-D Kim1, Y-J Cho, S-H Park

  • 1Kyungpook National University School of Medicine, Department of Internal Mediicne, Daegu, Republic of Korea. drcdkim@mail.cnu.ac.kr

Insights

Urinary betaig-h3 levels can indicate chronic cyclosporine nephrotoxicity (CyAN) progression or regression. This biomarker reflects kidney damage and improves after cyclosporine withdrawal, aiding in monitoring CyAN.

Area of Science:

  • Nephrology
  • Immunology
  • Biomarker Discovery

Background:

  • Chronic cyclosporine nephrotoxicity (CyAN) is a significant complication in organ transplantation.
  • Transforming growth factor (TGF)-beta plays a key role in CyAN pathogenesis.
  • TGF-beta induced gene h3 (betaig-h3) is upregulated by TGF-beta, suggesting its potential involvement.

Purpose of the Study:

  • To evaluate betaig-h3 as a sensitive urinary marker for monitoring chronic CyAN progression and regression.
  • To correlate urinary betaig-h3 levels with renal tissue findings in CyAN.

Main Methods:

  • Enzyme-linked immunosorbent assay (ELISA) was used to measure urinary betaig-h3 levels in patients with chronic CyAN and controls.
  • Tubulointerstitial fibrosis (TIF) was scored, and betaig-h3 expression was assessed in renal tissues via immunoperoxidase labeling.
  • Urinary betaig-h3 levels were monitored before and after cyclosporine (CyA) withdrawal or dosage reduction.

Main Results:

  • Urinary betaig-h3 levels were significantly higher in patients with chronic CyAN compared to controls.
  • A positive correlation was found between the degree of TIF and urinary betaig-h3 levels in CyAN patients.
  • Betaig-h3 expression was prominent in renal tissues affected by CyAN, particularly at the basement membranes of tubules and interstitium.
  • Urinary betaig-h3 levels decreased significantly after CyA discontinuation or reduction, despite stable serum creatinine.

Conclusions:

  • Urinary betaig-h3 is a sensitive biomarker for detecting chronic CyAN.
  • This marker can effectively monitor the progression and regression of CyAN.
  • Betaig-h3 may serve as a valuable tool for managing patients at risk of or experiencing cyclosporine-induced kidney damage.