Galectin-9 as a circulating marker of mesangial injury and prognosis in biopsy-proven kidney disease.

Authors

Ming-Tsun Tsai, Szu-Yuan Li, Donggun Kim, Jihwan Park, Insa M Schmidt, Runqi Zhao, Sushrut S Waikar, Tsung-Han Hsieh, Haichun Yang, Tz-Heng Chen, Shuo-Ming Ou, Ruey-Bing Yang

Published in

American journal of nephrology. Pages 1-24. Jul 29, 2026. Epub Jul 29, 2026.

Abstract

Introduction Galectin-9, a β-galactoside-binding protein, is elevated in various kidney diseases. While exogenous galectin-9 attenuates kidney injury in experimental models, it remains unclear whether endogenous plasma galectin-9 reflects renal histopathology and independently predicts long-term adverse outcomes in chronic kidney disease (CKD). Methods Plasma galectin-9 levels were prospectively measured in 366 participants from the Taipei Renal Transcriptomics and Outcomes Investigation (TRTOI) cohort. Renal histopathology and chronicity were assessed using a modified Mayo Clinic Chronicity Score (MCCS). Major adverse renal events (MAREs) were defined as ≥40% decline in eGFR, kidney failure, or death. Findings were validated in 549 participants from the Boston Kidney Biopsy Cohort (BKBC). In vitro, mouse mesangial cells (SV40-MES-13) were used to evaluate galectin-9 effects on TGF-β-induced mesangial activation. Results Transcriptomic analysis showed upregulation of LGALS9 (encoding galectin-9) in fibrotic kidneys. Plasma galectin-9 positively correlated with urine protein-to-creatinine ratio and MCCS, and inversely with eGFR. Elevated galectin-9 was independently associated with mesangial expansion. In vitro, exogenous galectin-9 attenuated TGF-β-induced mesangial cell activation, proliferation, and profibrotic responses; these effects were reversed by lactose, a competitive inhibitor of the carbohydrate recognition domains of galectin-9. In the TRTOI cohort, participants in the highest galectin-9 tertile had a significantly increased risk of MAREs, independent of confounders. Validation in the BKBC cohort confirmed that higher galectin-9 levels were independently associated with increased all-cause mortality. Conclusion Elevated plasma galectin-9 is associated with mesangial expansion and predicts a higher risk of MAREs in patients with CKD.

PMID:
42525588
Bibliographic data and abstract were imported from PubMed on 30 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.