High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients

Mario Rotondi, Giuseppe Stefano Netti, Elena Lazzeri, Giovanni Stallone, Elisabetta Bertoni, Luca Chiovato, Giuseppe Grandaliano, Loreto Gesualdo, Maurizio Salvadori, Francesco Paolo Schena, Paola Romagnani, Mario Serio

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Summary Several clinical and experimental models have underlined the role of the CXCR3-binding chemokines in the immune-mediated kidney diseases. This study aimed to investigate the predictive value of measuring pretransplant CXCL9 levels for acute rejection (AR) onset and kidney transplantation outcome. Pretransplantation serum levels of CXCL9 were tested retrospectively in 252 kidney graft recipients, whose stratification in two groups according to CXCL9 levels (272.1 pg/ml) showed highly significant differences in 5-year survival rates (97.7% vs. 73.3%; P <0.001). Multivariate analysis demonstrated that among the analysed variables, CXCL9 [relative risk (RR) 11.708] and AR (RR 3.604) had the highest predictive power of graft loss. Accordingly, patients with AR (254.4 ± 22.1; P <0.05) and, even more, those with anti-thymoglobulin (ATG)-treated AR also showed increased pretransplant serum CXCL9 levels (319.3 ± 28.1, P <0.001). Moreover, CXCL9 expression and distribution were investigated in tissue specimens obtained from 10 patients affected by AR, and wide CXCL9 expression was detected not only in infiltrating inflammatory cells but also in vascular and tubular structures. Measurement of pretransplant serum CXCL9 levels might represent the tracking of a clinically useful parameter to identify subjects at high risk of AR and graft failure. These findings might be used for the individualization of immunosuppressive therapies.

Original languageEnglish
Pages (from-to)465-475
Number of pages11
JournalTransplant International
Volume23
Issue number5
DOIs
Publication statusPublished - 2010

Fingerprint

Graft Rejection
Renal Insufficiency
Transplants
Serum
Kidney Diseases
Immunosuppressive Agents
Chemokines
Kidney Transplantation
Blood Vessels
Theoretical Models
Multivariate Analysis
Survival Rate
Kidney
Therapeutics

Keywords

  • Acute rejection
  • Chemokine receptor CXCR3
  • CXCL9
  • Renal allograft survival
  • Renal graft loss
  • Renal graft outcome

ASJC Scopus subject areas

  • Transplantation
  • Medicine(all)

Cite this

High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients. / Rotondi, Mario; Netti, Giuseppe Stefano; Lazzeri, Elena; Stallone, Giovanni; Bertoni, Elisabetta; Chiovato, Luca; Grandaliano, Giuseppe; Gesualdo, Loreto; Salvadori, Maurizio; Schena, Francesco Paolo; Romagnani, Paola; Serio, Mario.

In: Transplant International, Vol. 23, No. 5, 2010, p. 465-475.

Research output: Contribution to journalArticle

Rotondi, M, Netti, GS, Lazzeri, E, Stallone, G, Bertoni, E, Chiovato, L, Grandaliano, G, Gesualdo, L, Salvadori, M, Schena, FP, Romagnani, P & Serio, M 2010, 'High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients', Transplant International, vol. 23, no. 5, pp. 465-475. https://doi.org/10.1111/j.1432-2277.2009.01006.x
Rotondi, Mario ; Netti, Giuseppe Stefano ; Lazzeri, Elena ; Stallone, Giovanni ; Bertoni, Elisabetta ; Chiovato, Luca ; Grandaliano, Giuseppe ; Gesualdo, Loreto ; Salvadori, Maurizio ; Schena, Francesco Paolo ; Romagnani, Paola ; Serio, Mario. / High pretransplant serum levels of CXCL9 are associated with increased risk of acute rejection and graft failure in kidney graft recipients. In: Transplant International. 2010 ; Vol. 23, No. 5. pp. 465-475.
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AU - Rotondi, Mario

AU - Netti, Giuseppe Stefano

AU - Lazzeri, Elena

AU - Stallone, Giovanni

AU - Bertoni, Elisabetta

AU - Chiovato, Luca

AU - Grandaliano, Giuseppe

AU - Gesualdo, Loreto

AU - Salvadori, Maurizio

AU - Schena, Francesco Paolo

AU - Romagnani, Paola

AU - Serio, Mario

PY - 2010

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N2 - Summary Several clinical and experimental models have underlined the role of the CXCR3-binding chemokines in the immune-mediated kidney diseases. This study aimed to investigate the predictive value of measuring pretransplant CXCL9 levels for acute rejection (AR) onset and kidney transplantation outcome. Pretransplantation serum levels of CXCL9 were tested retrospectively in 252 kidney graft recipients, whose stratification in two groups according to CXCL9 levels (272.1 pg/ml) showed highly significant differences in 5-year survival rates (97.7% vs. 73.3%; P <0.001). Multivariate analysis demonstrated that among the analysed variables, CXCL9 [relative risk (RR) 11.708] and AR (RR 3.604) had the highest predictive power of graft loss. Accordingly, patients with AR (254.4 ± 22.1; P <0.05) and, even more, those with anti-thymoglobulin (ATG)-treated AR also showed increased pretransplant serum CXCL9 levels (319.3 ± 28.1, P <0.001). Moreover, CXCL9 expression and distribution were investigated in tissue specimens obtained from 10 patients affected by AR, and wide CXCL9 expression was detected not only in infiltrating inflammatory cells but also in vascular and tubular structures. Measurement of pretransplant serum CXCL9 levels might represent the tracking of a clinically useful parameter to identify subjects at high risk of AR and graft failure. These findings might be used for the individualization of immunosuppressive therapies.

AB - Summary Several clinical and experimental models have underlined the role of the CXCR3-binding chemokines in the immune-mediated kidney diseases. This study aimed to investigate the predictive value of measuring pretransplant CXCL9 levels for acute rejection (AR) onset and kidney transplantation outcome. Pretransplantation serum levels of CXCL9 were tested retrospectively in 252 kidney graft recipients, whose stratification in two groups according to CXCL9 levels (272.1 pg/ml) showed highly significant differences in 5-year survival rates (97.7% vs. 73.3%; P <0.001). Multivariate analysis demonstrated that among the analysed variables, CXCL9 [relative risk (RR) 11.708] and AR (RR 3.604) had the highest predictive power of graft loss. Accordingly, patients with AR (254.4 ± 22.1; P <0.05) and, even more, those with anti-thymoglobulin (ATG)-treated AR also showed increased pretransplant serum CXCL9 levels (319.3 ± 28.1, P <0.001). Moreover, CXCL9 expression and distribution were investigated in tissue specimens obtained from 10 patients affected by AR, and wide CXCL9 expression was detected not only in infiltrating inflammatory cells but also in vascular and tubular structures. Measurement of pretransplant serum CXCL9 levels might represent the tracking of a clinically useful parameter to identify subjects at high risk of AR and graft failure. These findings might be used for the individualization of immunosuppressive therapies.

KW - Acute rejection

KW - Chemokine receptor CXCR3

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KW - Renal allograft survival

KW - Renal graft loss

KW - Renal graft outcome

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