Circulating Activin A, Kidney Fibrosis, and Adverse Events

Ming Tsun Tsai, Shuo Ming Ou, Kuo Hua Lee, Chih Ching Lin, Szu Yuan Li*

*此作品的通信作者

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)

摘要

BackgroundIdentification of reliable biomarkers to assess kidney fibrosis severity is necessary for patients with CKD. Activin A, a member of the TGF-β superfamily, has been suggested as a biomarker for kidney fibrosis. However, its precise utility in this regard remains to be established.MethodsWe investigated the correlation between plasma activin A levels, kidney fibrosis severity, and the incidence of major adverse kidney events in patients who underwent native kidney biopsies at a tertiary medical center. We performed RNA sequencing and histological analyses on kidney biopsy specimens to assess activin A expression. In vitro experiments were also conducted to explore the potential attenuation of TGF-β-induced fibroblast activation through activin A inhibition.ResultsA total of 339 patients with biopsy-confirmed kidney diseases were enrolled. Baseline eGFR was 36 ml/min per 1.73 m2, and the urine protein/creatinine ratio was 2.9 mg/mg. Multivariable logistic regression analysis revealed a significant association between plasma activin A levels and the extent of tubulointerstitial fibrosis. Our RNA sequencing data demonstrated a positive correlation between kidney INHBA expression and plasma activin A levels. Furthermore, the histological analysis showed that myofibroblasts were the primary activin A-positive interstitial cells in diseased kidneys. During a median follow-up of 22 months, 113 participants experienced major adverse kidney events. Cox proportional hazards analysis initially found a positive association between plasma activin A levels and kidney event risk, but it became insignificant after adjusting for confounders. In cultured fibroblasts, knockdown of activin A significantly attenuated TGF-β-induced fibroblast-myofibroblast conversion.ConclusionsPlasma activin A levels correlate with kidney fibrosis severity and adverse outcomes in various kidney disorders.

原文English
頁(從 - 到)169-177
頁數9
期刊Clinical journal of the American Society of Nephrology : CJASN
19
發行號2
DOIs
出版狀態Published - 2月 2024

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