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In last years, antibody-mediated rejection (AbMR) has been identified as the leading cause of death-censored graft loss of kidney transplants. Despite the growing recognition of the role of the B-lymphocyte subpopulation in the development of both tolerance and rejection, little is known about the trigger mechanisms and effectors of this humoral response. The B-cell activating factor BAFF contributes to the development and maturation of B-lymphocytes, but current data about its role in the generation of donor-specific antibodies (DSA) and in the subsequent appearance of AbMR are inconsistent.We performed a prospective study including both indication and one-year protocol kidney transplant biopsies carried out in our center between January/2015 and February/2017. Serum samples were collected at the day of the graft biopsy and one month later and soluble BAFF levels were measured by ELISA.60 biopsies were performed at a median time of 1.11 year (IQR 098, 1.99 years). Median soluble BAFF levels were 445 pg/ml (IQR 318, 630). AbMR was diagnosed in 30 biopsies. Area under the ROC curve of soluble BAFF for predicting AbMR was 0.661 (95%CI 0.521-0.800, p = 0.033). Mean values of soluble BAFF were significantly higher in patients with AbMR (588 ± 312 pg/ml vs. 416 ± 177 pg/ml, p = 0.033). Mean values of soluble BAFF were significantly higher in patients with DSA (605 ± 259 pg/ml vs. 428 ± 249 pg/ml, p = 0.005). BAFF levels related to Banff scores g (r = 0.376, p = 0.003) and cg (r = 0.351, p = 0.007) and to albuminuria (r = 0.403, p = 0.003). One-month post-biopsy serum BAFF levels were lower in 6 patients who receive IVIG therapy but without reaching statistically significant differences (-87 ± 139 pg/ml vs. 40 ± 127 pg/ml, p = 0.062).Serum soluble BAFF levels show a moderate ability to predict the diagnosis of AbMR in a kidney graft biopsy. Higher BAFF levels in patients with DSA and AbMR suggest that BAFF contributes to the pathogenesis of antibody-mediated graft damage. BAFF related graft injury is more prominent in the glomerular compartment. IVIG mechanism of action in AbMR therapy can be partly mediated through BAFF reduction.This work was partially supported by grants for Fondo de Investigaciones Sanitarias-ISCIII (PI1100990, PI1400378, PI1601585, and RD16/0009/0027) and IDIVAL.