Abstract

Background: Galectin-3 is associated with kidney fibrosis and kidney function decline in the general population. We aimed to study the association of galectin-3 with long-term risk of graft failure in a cohort of extensively phenotyped kidney transplant recipients (KTR). Methods: We performed a longitudinal cohort study in 561 KTR without heart failure and with a functioning graft ≥1 year. Kaplan-Meier curve, log-rank test, and multivariableadjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of baseline serum galectin-3 with death-censored graft failure (defined as restart of dialysis or re-transplantation). Subgroup prospective analyses were performed according to significant effect-modifiers. Results: Median galectin-3 was 21.1 (IQR, 17.0-27.2) ng/mL. During a median follow-up of 9.5 (IQR, 6.2-10.2) years, 72 KTR developed graft failure, with significantly different distribution of events across tertiles of galectin-3 (P<0.001). In multivariable Cox regression analyses, galectin-3 associated with graft failure (HR, 2.13 per 1-SD increase; 95% CI, 1.61-2.80, P<0.001), independent of well-established general and transplant-specific risk factors, including eGFR and proteinuria. Particularly strong associations were found in patients with systolic blood pressure ≥140 mmHg (HR, 2.29 per 1-SD increase; 95% CI 1.80-2.92, P<0.001) and in former or current smokers (HR, 2.56 per 1-SD increase; 95% CI 1.95-3.37, P<0.001). Conclusions: In stable KTR, galectin-3 levels are elevated and independently associated with higher risk of graft failure at 10-years of follow-up. These results underline novel opportunities to monitor patients, target pharmacological therapy, and decrease the burden of long-term graft failure in stable KTR.