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.