*3.3. Urinary and Serum Chemokines*

IFN-γ induced urinary C-X-C motif chemokine ligand 9 (CXCL9) and 10 (CXCL10) chemokines are associated with Th-1 immune response and involved in T cell recruitment in inflammatory processes. They are promising as biomarkers for TCMR and ABMR [62,66].

Low levels are associated with immunological quiescence, as shown by their very high NPP, which makes them an ideal tool to rule out rejection, including subclinical ones, and to identify transplant recipients at low immunological risk [63]. This was especially evident for CXCL 9 (CTOT-01 study), which was associated with acute TCMR within the first year.

However, a subsequent study with a longer follow-up (CTOT-17) showed that changes in eGFR between 3 or 6 months and 24 months better predicted 5-year graft loss than CXCL-9 measurement [64].

Association of urinary CXCL10-to-creatinine ratio with DSA improved identification of ABMR and prediction of graft loss. In a recent study, higher blood and urine levels of both CXCL9 and CXCL10 were found in ABMR, but urinary CXCL9 was the most accurate biomarker of rejection (AUC of ROC: 0.77) and—if measured in combination with immunodominant DSA mean fluorescence intensity (MFI)—it allowed a net reclassification increase of 73% compared to DSA MFI alone [65].
