☆ 4.6 Article

Identification of Galectin-3 as Potential Biomarkers for Renal Fibrosis by RNA-Sequencing and Clinicopathologic Findings of Kidney Biopsy

FRONTIERS IN MEDICINE (2021)

Journal

FRONTIERS IN MEDICINE

Volume 8, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA

DOI: 10.3389/fmed.2021.748225

Keywords

galectin-3; chronic kidney disease; tubular atrophy; interstitial fibrosis; kidney biopsy; RNA-sequencing analysis

Funding

Ministry of Science and Technology, Taiwan [AS-CFII-108-118, MOST 107-2314-B-075-052, MOST 108-2314-B-075-008, MOST 109-2314-B-075-067-MY3, MOST 109-2320-B-075-006, MOST 110-2321-B-A49-003]
Taipei Veterans General Hospital [V107B-027, V108B-023, V108C-103, V108D42-004-MY3-1, V108D42-004-MY3-2, V108D42-004-MY3-3, V109B-022, V109C-114, V109D50-001-MY3-1, V109D50-001-MY3-2, V110C-152, V110E-003-2]
Taipei, Taichung, Kaohsiung Veterans General Hospital, Tri-Service General Hospital, Academia Sinica Joint Research Program [VTA110-V1-3-1]
Taipei Veterans General Hospital-National Yang-Ming University Excellent Physician Scientists Cultivation Program [104-V-B-044]
Institute of Biomedical Sciences, Academia Sinica [IBMS-CRC110-P04, AS-VTA-110-03]
Foundation for Poison Control [FPC-109-002]
[MOST 106-2314-B-010-039-MY3]

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Abstract

The study revealed that plasma Gal-3 levels are inversely correlated with eGFR but positively correlated with renal fibrosis, potentially involving immune response and associated pathways, supporting the role of Gal-3 as a predictive marker of renal fibrosis.

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis.Method: In 249 patients (male/female: 155/94, age: 57.2 +/- 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients.Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 +/- 628.1 pg/mL vs. 811.6 +/- 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion.Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.

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A Higher Foci Density of Interstitial Fibrosis and Tubular Atrophy Predicts Progressive CKD after a Radical Nephrectomy for Tumor

Luisa Ricaurte Archila, Aleksandar Denic, Aidan F. Mullan, Ramya Narasimhan, Marija Bogojevic, R. Houston Thompson, Bradley C. Leibovich, S. Jeson Sangaralingham, Maxwell L. Smith, Mariam P. Alexander, Andrew D. Rule

Summary: IF/TA density (the number of IF/TA foci per area of cortex) predicts progressive CKD and noncancer mortality after nephrectomy, independent of the percentage of IF/TA. A higher density of IF/TA foci suggests more scattered damage to the nephrons and worse kidney prognosis at the same percentage of IF/TA.

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2021)