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Urinary transforming growth factor-beta-induced gene-h3 (betaig-h3) as a sensitive predictor in chronic cyclosporine
1Kyungpook National University School of Medicine, Department of Internal Mediicne, Daegu, Republic of Korea. drcdkim@mail.cnu.ac.kr
Abstract:
Transforming growth factor (TGF)-beta is involved in the pathogenesis of chronic cyclosporine nephrotoxicity (CyAN). Since the expression of TGF-beta induced gene h3 (betaig-h3) is up-regulated by TGF-beta, we evaluated the potential role of betaig-h3 as a sensitive urinary marker to monitor the progression/regression of chronic CyAN. Urinary betaig-h3 levels were determined using an enzyme-linked immunosorbent assay in nine patients with chronic CyAN and 13 patients with stable graft function. We scored the extent of tubulointerstitial fibrosis (TIF) and using immunoperoxidase labeling, determined betaig-h3 expression in renal tissues of patients with chronic CyAN. Urinary betaig-h3 excretion was higher in chronic CyAN compared to control subjects (173.4+/-26.0 vs 62.6+/-5.0 ng/mg creatinine, P<.01). In chronic CyAN, the degree of TIF correlated with increased urinary betaig-h3 levels (r=.785, P<.05). In kidneys with chronic CyAN, betaig-h3 labeling was more prominent at the basement membranes (BM) of the tubules where inflammatory cells had infiltrated the surrounding interstitium. Moreover, the BM of the atrophied tubules and their surrounding interstitium were strongly labeled. Urinary betaig-h3 levels decreased from 173.4+/-26.0 to 64.9+/-14.4 ng/mg creatinine at 1 month after discontinuation of CyA or reduction in CyA dosage (P<.01) despite unchanged serum creatinine levels. Urinary betaig-h3 levels increased in patients with chronic CyAN and decreased after discontinuation or reduction of CyA dosage. Our results suggested that urinary betaig-h3 levels could be used as a sensitive urinary marker to monitor the progression or regression of chronic CyAN.
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.
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