4.5 Article

Plasma Galectin-9 Is a Useful Biomarker for Predicting Renal Function in Patients Undergoing Native Kidney Biopsy

Journal

ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
Volume 147, Issue 2, Pages 167-176

Publisher

COLL AMER PATHOLOGISTS
DOI: 10.5858/arpa.2021-0466-OA)

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Plasma galectin-9 levels are associated with varying stages of chronic kidney disease (CKD), and high levels are correlated with older age, decreased renal function, increased proteinuria, and greater interstitial fibrosis. In renal tissue, galectin-9 expression is positively correlated with plasma galectin-9 levels and is mainly expressed in macrophages.
center dot Context.& mdash;Galectin-9 reduces tissue damage in certain immune-mediated glomerular diseases. However, its role in structural and functional renal changes in patients with varying types of chronic kidney disease (CKD) is less clear.Objective.& mdash;To investigate the association between plasma galectin-9 levels, proteinuria, tubulointerstitial lesions, and renal function in different CKD stages.Design.& mdash;We measured plasma galectin-9 levels in 243 patients undergoing renal biopsy for determining the CKD etiology. mRNA and protein expression levels of intrarenal galectin-9 were assessed by quantitative real-time poly-merase chain reaction and immunostaining. Relationships between plasma galectin-9, clinical characteristics, and tubulointerstitial damage were analyzed with logistic regression. We investigated galectin-9 expression patterns in vitro in murine J774 macrophages treated with differing stimuli.Results.& mdash;To analyze the relationship between galectin-9 and clinical features, we divided the patients into 2 groups according to median plasma galectin-9 levels. The high galectin-9 group tended to be older and to have decreased renal function, higher proteinuria, and greater interstitial fibrosis. After multivariable adjustment, elevat-ed plasma galectin-9 levels were independently associated with stage 3b or higher CKD. An analysis of gene expression in the tubulointerstitial compartment in the biopsy samples showed a significant positive correlation between intrarenal galectin-9 mRNA expression and plasma galectin-9 levels. Immunohistochemistry confirmed increased galectin-9 expression in the renal interstitium of patients with advanced CKD, and most galectin-9-positive cells were macrophages, as determined by double-immu-nofluorescence staining. In vitro experiments showed that galectin-9 expression in macrophages was significantly increased after interferon -c stimulation.Conclusions.& mdash;Our findings suggest that plasma galec-tin-9 is a good biomarker for diagnosing advanced CKD.

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