Circulating Activin A, Kidney Fibrosis, and Adverse Events
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY(2024)
摘要
Background Identification of reliable biomarkers to assess kidney fibrosis severity is necessary for patients with CKD. Activin A, a member of the TGF-beta superfamily, has been suggested as a biomarker for kidney fibrosis. However, its precise utility in this regard remains to be established. Methods We 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-beta-induced fibroblast activation through activin A inhibition. Results A 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-beta-induced fibroblast-myofibroblast conversion. Conclusions Plasma activin A levels correlate with kidney fibrosis severity and adverse outcomes in various kidney disorders.
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关键词
CKD,renal biopsy,renal fibrosis
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