Galectin-3 and Risk of Late Graft Failure in Kidney Transplant Recipients: A 10-years Prospective Cohort StudySotomayor, C. G., Te Velde-Keyzer, C. A., Diepstra, A., van Londen, M., Pol, R. A., Post, A., Gans, R. O. B., Nolte, I. M., Slart, R. H. J. A., de Borst, M. H., Berger, S. P., Rodrigo, R., Navis, G. J., de Boer, R. A. & Bakker, S. J. L., 25-Jun-2020, In : Transplantation. 38 p.
Research output: Contribution to journal › Article › Academic › peer-review
- Groningen Kidney Center (GKC)
- Stem Cell Aging Leukemia and Lymphoma (SALL)
- Groningen Institute for Organ Transplantation (GIOT)
- Lifestyle Medicine (LM)
- Lifelong Learning, Education & Assessment Research Network (LEARN)
- Life Course Epidemiology (LCE)
- Cardiovascular Centre (CVC)
- Translational Immunology Groningen (TRIGR)
- Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
- Value, Affordability and Sustainability (VALUE)
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 (IQR, 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 graft failure (restart of dialysis or retransplantation).
RESULTS: Among 561 KTR (age 52 ± 12 years; 54% males), baseline median galectin-3 was 21.1 (IQR, 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 (HR per 1-SD change, 2.12; 95%CI 1.63-2.75; P<0.001), particularly among KTR with systolic blood pressure ≥140mmHg (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.
|Number of pages||38|
|Publication status||E-pub ahead of print - 25-Jun-2020|