Elevation of CXCR3-Binding Chemokines in Urine Indicates Acute Renal-Allograft Dysfunction

Abstract

A noninvasive urinary test that diagnoses acute renal allograft dysfunction would benefit renal transplant patients. We aimed to develop a rapid urinary diagnostic test by detecting chemokines. Seventythree patients with renal allograft dysfunction prompting biopsy and 26 patients with stable graft function were recruited. Urinary levels of CXCR3-binding chemokines, monokine induced by IFN-c (Mig/CXCL9), IFN-c -induced protein of 10 kDa (IP-10/CXCL10), and IFN-inducible T-cell chemoattractant (I-TAC/CXCL11), were determined by a particle-based triplex assay. IP-10, Mig and I-TAC were significantly elevated in renal graft recipients with acute rejection, acute tubular injury and BK virus nephritis. Using 100 pg/mL as the threshold level, both IP-10 and Mig had diagnostic value (sensitivity 86.4%; specificity 91.3%) in differentiating acute graft dysfunction from other clinical conditions. In terms of monitoring the response to antirejection therapy, this urinary test is more sensitive and predictive than serum creatinine. These results indicate that this rapid test is clinically useful.

Prediction of Acute Renal Allograft Rejection by Urinary Monokine Induced by IFN-γ (MIG)

“…Urinary measurements of MIG in a small number of pediatric patients (33) and in adult renal allograft patients support our data (34,35). Nevertheless, so far no study has shown the day-to-day value of urinary CXCR3 ligand measurements in a nonselected group of de novo NTX patients and the predictive value of MIG in urine for the diagnosis of AR.…”

“…Similar to MIG, but to a lesser extent, high urinary IP-10 correlated well with AR as shown previously (34). It is intriguing, however, that the upregulation of IP-10 gene activity might not be that strictly dependent on IFN and has also been associated with alloantigen-independent organ damage (37,38).…”

CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow

“…38,39 Studies in diverse tissues including the brain, liver, and lung suggest that CXCR3 does not provide a tissue-specific signal for lymphocyte recruitment but is associated with infiltration of inflamed tissues regardless of the anatomical site. 36,40,41 Although these studies have shown expression of CXCR3 ligands associated with CXCR3 ϩ lymphocytes in inflammatory disease, functional studies have been limited to demonstrating that lymphocytes isolated from diseased tissues undergo chemotaxis to CXCR3 ligands. 21 In the present study we found increased expression of all three CXCR3 ligands in several different chronic inflammatory liver diseases whereas the levels in normal liver were minimal.…”

Citocinas e quimiocinas no transplante renal

“…36 A elevação urinária do TGF-b tem sido associada também ao grau de fibrose intersticial na IF/TA. 52,53 Hu et al, 54 analisando amostras únicas de urina pré-biópsia renal de 99 pacientes, demonstraram elevação de I-TAC/CXCL11, MIG/CXCL9 e IP-10/ CXCL10 em vigência de RA, nefropatia por poliomavírus e NTA, mas não em casos de rejeição borderline, IF/TA e função estável de enxerto. MIG/CXCL9 e IP-10/CXCL10 apresentaram ní-veis mais elevados, com sensibilidade de 88,6% e especificidade de 87% para diagnóstico das complicações mencionadas.…”

“…MIG/CXCL9 e IP-10/CXCL10 apresentaram ní-veis mais elevados, com sensibilidade de 88,6% e especificidade de 87% para diagnóstico das complicações mencionadas. 54 Ressalta-se ainda que, com o tratamento da RA, os níveis urinários de MIG/CXCL9 e IP-10/CXCL10 se reduziram dias antes da diminuição da creatinina sanguínea. IP-10/CXCL10 urinária se reduziu em todos os pacientes 2 a 5 dias antes da diminuição da creatinina sérica.…”