Urinary CXCL9 and CXCL10 Levels Correlate with the Extent of Subclinical Tubulitis

Schaub, Stefan; Nickerson, Peter; Rush, David; Mayr, Michael; Hess, Christoph; Golian, Mehrdad; Stefura, William P.; HayGlass, Kent T.

doi:10.1111/j.1600-6143.2009.02645.x

Cited by 140 publications

(127 citation statements)

References 23 publications

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“…For example, in the extensive analysis conducted by the Winnipeg group, the urine CXCL10 level was associated with tubulitis, a feature of TCMR. 4,10,11 In addition, in the recent CTOT-01 Study that validated urinary CXCL9 as a diagnostic biomarker of AR, only six biopsies showed evidence of ABMR. Urinary CXCL9 and CXCL10 levels have also been shown to be diagnostic of BK virus-associated nephropathy.…”

Section: Discussionmentioning

confidence: 99%

“…Schaub et al 10 first reported the association of CXCL9 and CXCL10, normalized to urine creatinine, with tubulitis. 10 A recent multicenter observational trial in 280 patients with kidney transplants reported that the CXCL9 protein level had a strong predictive value for noninvasively diagnosing TCMR. 5 Although there have been improvements in diagnosing TCMR using these new methods, it is noteworthy that, at the same time, the clinical presentation of renal allograft rejection has changed dramatically, with the incidence of TCMR progressively decreasing to 10%-15% using tacrolimus-based immunosuppression.…”

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confidence: 99%

“…Protein markers have also been assessed for their ability to predict both clinical [3][4][5][6][7] and subclinical TCMR. 4,[8][9][10][11] C-X-C motif chemokine 9 (CXCL9) and CXCL10 are IFNg-dependent, C-X-C motif chemokine receptor 3-binding chemokines that are secreted by infiltrating inflammatory cells and renal tubular and mesangial cells. Schaub et al 10 first reported the association of CXCL9 and CXCL10, normalized to urine creatinine, with tubulitis.…”

mentioning

confidence: 99%

“…4,[8][9][10][11] C-X-C motif chemokine 9 (CXCL9) and CXCL10 are IFNg-dependent, C-X-C motif chemokine receptor 3-binding chemokines that are secreted by infiltrating inflammatory cells and renal tubular and mesangial cells. Schaub et al 10 first reported the association of CXCL9 and CXCL10, normalized to urine creatinine, with tubulitis. 10 A recent multicenter observational trial in 280 patients with kidney transplants reported that the CXCL9 protein level had a strong predictive value for noninvasively diagnosing TCMR.…”

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confidence: 99%

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Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody–Mediated Kidney Allograft Rejection

Rabant

Amrouche

Lebreton³

et al. 2015

Journal of the American Society of Nephrology

115

112

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Urinary levels of C-X-C motif chemokine 9 (CXCL9) and CXCL10 can noninvasively diagnose T cellmediated rejection (TCMR) of renal allografts. However, performance of these molecules as diagnostic/ prognostic markers of antibody-mediated rejection (ABMR) is unknown. We investigated urinary CXCL9 and CXCL10 levels in a highly sensitized cohort of 244 renal allograft recipients (67 with preformed donor-specific antibodies [DSAs]) with 281 indication biopsy samples. We assessed the benefit of adding these biomarkers to conventional models for diagnosing/prognosing ABMR. Urinary CXCL9 and CXCL10 levels, normalized to urine creatinine (Cr) levels (CXCL9:Cr and CXCL10:Cr) or not, correlated with the extent of tubulointerstitial (i+t score; all P,0.001) and microvascular (g+ptc score; all P,0.001) inflammation. CXCL10:Cr diagnosed TCMR (area under the curve [AUC]=0.80; 95% confidence interval [95% CI], 0.68 to 0.92; P,0.001) and ABMR (AUC=0.76; 95% CI, 0.69 to 0.82; P,0.001) with high accuracy, even in the absence of tubulointerstitial inflammation (AUC=0.70; 95% CI, 0.61 to 0.79; P,0.001). Although mean fluorescence intensity of the immunodominant DSA diagnosed ABMR (AUC=0.75; 95% CI, 0.68 to 0.82; P,0.001), combining urinary CXCL10:Cr with immunodominant DSA levels improved the diagnosis of ABMR (AUC=0.83; 95% CI, 0.77 to 0.89; P,0.001). At the time of ABMR, urinary CXCL10:Cr ratio was independently associated with an increased risk of graft loss. In conclusion, urinary CXCL10:Cr ratio associates with tubulointerstitial and microvascular inflammation of the renal allograft. Combining the urinary CXCL10:Cr ratio with DSA monitoring significantly improves the noninvasive diagnosis of ABMR and the stratification of patients at high risk for graft loss.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Urinary C-X-C Motif Chemokine 10 Independently Improves the Noninvasive Diagnosis of Antibody–Mediated Kidney Allograft Rejection

Rabant

Amrouche

Lebreton³

et al. 2015

Journal of the American Society of Nephrology

115

112

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“…Levels of circulating MMPs and TIMPs fluctuate in SLE, and increased MMP-2, MMP-3, MMP-7, TIMP-1 and TIMP-2 probably reflect an aggravated Effective for the early detection and prognosis of several acute kidney diseases [27] Yao Xu [28] ; Michael R. Bennett [13] CXCL9/CXCL10 Urinary CXCL9 promising for clinical decision-making following kidney transplantation Noninvasive biomarkers to screen for subclinical tubulitis [29] Hricik DE [14] ; Rabant M [30] ; Paola Romagnani [31] [TIMP-2 ]* [IGFBP7]…”

Section: T-cell Immunoglobulin Domainmentioning

confidence: 99%

Urine biomarkers in renal allograft

Wang

Lin

Yuan

et al. 2016

Journal of Translational Internal Medicine

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There is a high risk for the survival of patients with an end-stage renal disease for kidney transplantation. To avoid rejection by strict medication adherence is of utmost importance to avoid the failure of a kidney transplant. It is imperative to develop non-invasive biomarkers to assess immunity risk, and to ultimately provide guidance for therapeutic decision-making following kidney transplantation. Urine biomarkers may represent the promising non-invasive tools that will help in predicting risk or success rates of kidney transplantations. Furthermore, composite urinary biomarkers or urinary biomarker panel array might be critical in improving the sensitivity and specificity in reflecting various risks of kidney failure during transplantation. This review primarily focuses on the role of such biomarkers in predicting chronic kidney disease (CKD) progression and/or cardiovascular disease (CVD) risk in renal allograft.

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