Validation of Urinary CXCL10 As a Marker of Borderline, Subclinical, and Clinical Tubulitis

Ho, Julie; Rush, David; Karpinski, Martin; Storsley, Leroy; Gibson, Ian W.; Bestland, Jennifer; Gao, Ang; Stefura, William P.; HayGlass, Kent T.; Nickerson, Peter

doi:10.1097/tp.0b013e31822d4de1

Cited by 70 publications

(83 citation statements)

References 32 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%

“…Suthanthiran et al 2 recently showed that the urinary cell mRNA profile can serve as a diagnostic and prognostic biomarker of TCMR. 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.…”

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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

118

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%

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

118

112

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“…rejection and polyomavirus-BK nephropathy) (12)(13)(14). Furthermore, it correlated with the extent of subclinical tubulitis in two independent patient cohorts (15,16).…”

Section: Introductionmentioning

confidence: 96%

“…A key limitation of these studies is that they included selected patient groups (12)(13)(14)(15)(16). As a consequence, the frequency of the investigated pathologies did not reflect real life, and thus cut-off determination of urinary CXCL10 for prediction of clinical/subclinical allograft inflammation and calculation of its diagnostic characteristics is problematic.…”

Section: Introductionmentioning

confidence: 99%

Detection of Clinical and Subclinical Tubulo-Interstitial Inflammation by the Urinary CXCL10 Chemokine in a Real-Life Setting

Hirt‐Minkowski

Amico

et al. 2012

American Journal of Transplantation

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Urinary CXCL10 is a promising noninvasive biomarker for tubulo-interstitial allograft inflammation, but its diagnostic characteristics have not been assessed in a real-life setting. We investigated urinary CXCL10 in 213 consecutive renal allograft recipients having 362 surveillance biopsies at 3/6 months and 80 indication biopsies within the first year posttransplant. Allograft histology results were classified as (i) acute Banff score zero, (ii) interstitial infiltrates only, (iii) tubulitis t1, (iv) tubulitis t2-3 and (v) isolated vascular compartment inflammation. For clinical and subclinical pathologies, urinary CXCL10 correlated well with the extent of tubulo-interstitial inflammation. To determine diagnostic characteristics of urinary CXCL10, histological groups were separated into two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (i.e. tubulitis t1-3 and isolated vascular compartment inflammation). For subclinical pathologies, AUC was 0.69 (sensitivity 61%, specificity 72%); for clinical pathologies, AUC was 0.74 (sensitivity 63%, specificity 80%). A urinary CXCL10-guided biopsy strategy would have reduced performance of surveillance and indication biopsies by 61% and 64%, respectively. Missed (sub)clinical pathologies were mostly tubulitis t1 and isolated vascular compartment lesions. In real life, urinary CXCL10 had clinically useful diagnostic properties making it a candidate biomarker to guide allograft biopsies.

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“…3) Šlapimo CXCL10 kaip ankstyvą tubulito žymenį nagrinėjo Ho su bendraautoriais [11]. Tyrėjai lygino šlapimo CXCL10 koncentraciją suskirstę pacientus į šešias grupes pagal inksto biopsijos rezultatus: norma, intersticinė fibrozė/kanalėlių atrofija (IFKA), IFKA bei paribinis tubulitas, paribinis tubulitas, subklinikinis tubulitas ir klinikinis tubulitas.…”

Section: Chemokinai Ir Transplantato Atmetimasunclassified

Inksto Transplantato Pažeidimo Biožymenys

Mačionienė

Miglinas

2017

Medicinos Teorija Ir Praktika

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SANTRAUKAReikšminiai žodžiai: inksto transplantatas, biožymenys. Pacientams po inksto transplantacijos stebėti ir atmetimui diagnozuoti taikoma inksto transplantato biopsija, tačiau tai invazinis tyrimo metodas, esant indikacijoms, atliekamas atsižvelgiant į gana vėlyvus ir nespecifinius rodiklius -kreatinino koncentraciją kraujo serume arba proteinuriją. Ieškoma naujų neinvazinių transplantato pažeidimo žymenų, kurie leidžia anksčiau nustatyti transplantato pažeidimą ar diferencijuoti atmetimą nuo kitų transplantato funkcijos pablogėjimo priežas-čių. Vieni tokių perspektyvių žymenų -chemokinai 9 ir 10, įvairios mikro RNR molekulės (miRNR-10b, miRNR-10a ir miRNR-210) bei ankstyvi, bet nespecifiniai žymenys -NGAL ir KIM-1. Tikimasi, kad šie biožymenys leis anksčiau diagnozuoti transplantato pažeidimą ir skirti atitinkamą gydymą. ABSTRACTKey words: kidney transplantation, biomarkers. Kidney transplant biopsy is used to monitor patients after kidney transplantation ant to diagnose rejection, however, it is an invasive method, performed according to indications which are defined by the rather late and nonspecific indicators such as serum creatinine concentration or proteinuria. New noninvasive transplant injury markers are searched in order to detect transplant injury earlier or to differentiate rejection from other reasons of transplant dysfunction. One of such perspective markers are chemokines 9 and 10, various micro RNA molecules (miRNA-10b, miRNA-10a and miRNA-210) and early but nonspecific markers like NGAL and KIM-1. It is expected that these biomarkers will allow earlier detection of transplant injury and prescription of an adequate treatment. ĮVADASInkstų transplantacija daugumai lėtine inkstų liga sergančių pacientų yra optimalus gydymo būdas, leidžiantis jei ne visiškai, tai bent iš dalies susigrąžinti iki susirgimo inkstų liga buvusią gyvenimo kokybę. Kad pacientas po inksto transplantacijos galėtų gyventi visavertį gyvenimą ir išvengtų dažnų hospitalizacijų, nepaprastai svarbu tinkamai parinkti imunosupresinius vaistus, kad būtų užkirstas kelias inksto transplantato funkcijai pablogėti. Inksto transplantato pažeidimą gali sukelti tiek imunologinės priežastys (inksto transplantato pažeidimas), kuriam gydyti paprastai skiriama sustiprinta imunosupresija, tiek gausybė kitų priežasčių (kalcineurino inhibitorių toksiškumas, transplantato kraujotakos sutrikimai, virusinės, bakterinės infekcijos ir kt.), kurių gydymas dažnai būna priešingas -sumažinama imunosupresija. Dažniausiai naudojami inksto transplantato pažeidimą atspindintys žymenys -kreatinino koncentracijos padidėjimas, naujai atsiradusi proteinurija -yra nespecifiniai ir gana vėlyvi, todėl transplantato atmetimui diagnozuoti pagal priimtus Banff klasifikacijos kriterijus atliekama inksto transplantato biopsija ir nustatomi donorui specifiniai antikūnai [1].Inksto transplantato biopsija leidžia įvertinti, ar yra inksto transplantato atmetimo histologinių požymių, taip pat padeda nustatyti atmetimo tipą (humoralinis ar ląste-linis atmetimas). Pagal ta...

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Validation of Urinary CXCL10 As a Marker of Borderline, Subclinical, and Clinical Tubulitis

Cited by 70 publications

References 32 publications

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

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

Detection of Clinical and Subclinical Tubulo-Interstitial Inflammation by the Urinary CXCL10 Chemokine in a Real-Life Setting

Inksto Transplantato Pažeidimo Biožymenys

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