*Purpose: Cytokines and chemokines play a critical role in acute rejection after kidney transplantation and may be of importance in the quest for better diagnostic markers and new therapeutic strategies for rejection. In this study we evaluated 27 cytokines, chemokines and growth factors measured in peripheral blood for their associations with rejection types and specific histological lesions.

*Methods: All for-cause biopsies performed in our center between 07/08/2012 and 13/07/2016 (N=293 in 192 recipients) were included. In concomitant peripheral blood samples, 27 cytokines, chemokines and growth factors were measured through multiplex analysis. Expression differences in acute rejection types were evaluated using ANOVA and logistic regression analysis, corrected with mixed models for multiple sampling.

*Results: Expression of CXCL-10 and the MIP-1 family of chemokines (MIP-1alfa, MIP-1beta and RANTES), ligands to the CXCR3 and CCR5 receptors were importantly associated with ABMR and its individual histological lesions. Higher levels of these chemokines reflect the interferon-gamma signature associated with T helper 1 cells, monocytes, macrophages and NK cells in rejection. These changes are not observed in TCMR and borderline changes. The diagnostic performance of peripheral blood cytokine profiles seems insufficient to help in non-invasive monitoring, reaching ROC AUC of 74.4% (95% CI 63.9%-84.9%, p<0.0001) when combining TNF-alfa, CXCL10/IP-10, MIP-1beta, RANTES and basic-FGF in a multivariate model for diagnosis of ABMR vs no ABMR.

*Conclusions: This study contributes to a better understanding of the roles of cytokines in renal allograft rejection and might aid the development of new therapeutic tools.

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