#5591 CIRCULATING ACTIVIN A REFLECTS THE SEVERITY OF RENAL FIBROSIS IN BIOPSY-PROVEN KIDNEY DISEASES—THE TAIPEI RENAL BIOPSY COHORT STUDY

Abstract

Abstract Background and Aims Despite considerable evidence indicating circulating activin A as a novel renal biomarker, its performance for predicting the severity of renal fibrosis and major adverse renal events (MARE) has not yet been extensively studied. Method We sought to assess the relationship between plasma activin A, renal fibrosis severity, and incidence of MARE in 339 patients undergoing clinically indicated native renal biopsies. To determine the primary source of circulating activin A, RNA-sequencing and histological analyses were performed on kidney biopsy specimens from patients with chronic kidney disease (CKD). We also conducted in vitro experiments to investigate whether inhibiting endogenous activin A could attenuate TGF-β-mediated activation of cultured fibroblasts. Results The median baseline eGFR and proteinuria were 36 mL/min/1.73 m2 and 2.9 mg/mg creatinine, respectively. After multivariable adjustment, elevated plasma activin A was associated with the extent of renal fibrosis. Histological analysis showed increased activin A expression in kidney tissues from patients with CKD, mainly in interstitial myofibroblasts. RNA-sequencing of tubulointerstitial tissue from human biopsy samples also revealed a direct correlation between tissue activin A mRNA expression and plasma activin A levels. During a median follow-up of 22 months, 113 participants suffered MARE. Cox proportional hazards analysis revealed that plasma activin A was associated with higher risk of renal events; however, the association became insignificant after correcting for confounders. Results from in vitro studies demonstrated that knocking down activin A expression could prevent TGF-β-induced activation of NRK49F fibroblasts. Conclusion The findings of this study support activin A as a potential diagnostic and therapeutic target in fibrotic kidney disease.