Galectin-3 and Risk of Late Graft Failure in Kidney Transplant Recipients: A 10-year Prospective Cohort Study.

Abstract

BACKGROUND:

Galectin-3 may play a causal role in kidney inflammation and fibrosis, which may also be involved in the development of kidney graft failure. With novel galectin-3-targeted pharmacological therapies increasingly coming available, we aimed to investigate whether galectin-3 is associated with risk of late graft failure in kidney transplant recipients (KTR).

METHODS:

We studied adult KTR who participated in TransplantLines Insulin Resistance and Inflammation Biobank and Cohort Study, recruited in a university setting (2001-2003). Follow-up was performed for a median of 9.5 (interquartile range, 6.2-10.2) years. Overall and stratified (Pinteraction < 0.05) multivariable-adjusted Cox proportional-hazards regression analyses were performed to study the association of galectin-3 with risk of graft failure (restart of dialysis or retransplantation).

RESULTS:

Among 561 KTR (age 52 ± 12 y; 54% males), baseline median galectin-3 was 21.1 (interquartile range, 17.0-27.2) ng/mL. During follow-up, 72 KTR developed graft failure (13, 18, and 44 events over increasing tertiles of galectin-3). Independent of adjustment for donor, recipient, and transplant characteristics, galectin-3-associated with increased risk of graft failure (hazard ratios [HR] per 1 SD change, 2.12; 95% confidence interval [CI], 1.63-2.75; P < 0.001), particularly among KTR with systolic blood pressure ≥140 mmHg (HR, 2.29; 95% CI, 1.80-2.92; P < 0.001; Pinteraction = 0.01) or smoking history (HR, 2.56; 95% CI, 1.95-3.37; P < 0.001; Pinteraction = 0.03). Similarly, patients in the highest tertile of galectin-3 were consistently at increased risk of graft failure.

CONCLUSIONS:

Serum galectin-3 levels are elevated in KTR, and independently associated with increased risk of late graft failure. Whether galectin-3-targeted therapies may represent novel opportunities to decrease the long-standing high burden of late graft failure in stable KTR warrants further studies.

• Authors: Camilo G Sotomayor, Charlotte A Te Velde-Keyzer, Arjan Diepstra, Marco van Londen, Robert A Pol, Adrian Post, Rijk O B Gans, Ilja M Nolte, Riemer H J A Slart, Martin H de Borst, Stefan P Berger, Ramón Rodrigo, Gerjan J Navis, Rudolf A de Boer, Stephan J L Bakker
• Journal: Transplantation (Transplantation) Vol. 105 Issue 5 Pg. 1106-1115 (05 01 2021) ISSN: 1534-6080 [Electronic] United States
• PMID: 32639409 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.

Chemical References

• Biomarkers
• Blood Proteins
• Galectins
• LGALS3 protein, human

Topics

• Adult
• Aged
• Biomarkers (blood)
• Blood Proteins
• Female
• Galectins (blood)
• Humans
• Kidney Failure, Chronic (blood, diagnosis, etiology, therapy)
• Kidney Transplantation (adverse effects)
• Male
• Middle Aged
• Predictive Value of Tests
• Prospective Studies
• Renal Dialysis
• Reoperation
• Risk Assessment
• Risk Factors
• Time Factors
• Treatment Failure
• Up-Regulation