Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation

Andre I. David, Gennaro Selvaggi, Phillip Ruiz, Jeffrey Gaynor, Panagiotis Tryphonopoulos, Gary I. Kleiner, Jang I. Moon, Seigo Nishida, Peter A. Pappas, Lobella Conanan, Debbie Weppler, Violet Esquenazi, David M. Levi, Tomoaki Kato, Andreas G. Tzakis

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained. METHODS. Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient's DBS citrulline level. RESULTS. Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. ≥13 μmoles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4% and >99% respectively). Specificity was 54% to 74% in children and 83% to 88% in adults. CONCLUSIONS. Citrulline levels <13 μmoles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels ≥13μmoles/L practically rule out moderate or severe rejection.

Original languageEnglish
Pages (from-to)1077-1081
Number of pages5
JournalTransplantation
Volume84
Issue number9
DOIs
StatePublished - Nov 1 2007

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Citrulline
Transplantation
Bacteremia
Serum
Respiratory Tract Infections
Linear Models
Pediatrics
Transplants
Sensitivity and Specificity
Infection

Keywords

  • Acute cellular rejection
  • Citrulline
  • Dried blood spot
  • Small intestine transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation. / David, Andre I.; Selvaggi, Gennaro; Ruiz, Phillip; Gaynor, Jeffrey; Tryphonopoulos, Panagiotis; Kleiner, Gary I.; Moon, Jang I.; Nishida, Seigo; Pappas, Peter A.; Conanan, Lobella; Weppler, Debbie; Esquenazi, Violet; Levi, David M.; Kato, Tomoaki; Tzakis, Andreas G.

In: Transplantation, Vol. 84, No. 9, 01.11.2007, p. 1077-1081.

Research output: Contribution to journalArticle

David, AI, Selvaggi, G, Ruiz, P, Gaynor, J, Tryphonopoulos, P, Kleiner, GI, Moon, JI, Nishida, S, Pappas, PA, Conanan, L, Weppler, D, Esquenazi, V, Levi, DM, Kato, T & Tzakis, AG 2007, 'Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation', Transplantation, vol. 84, no. 9, pp. 1077-1081. https://doi.org/10.1097/01.tp.0000287186.04342.82
David, Andre I. ; Selvaggi, Gennaro ; Ruiz, Phillip ; Gaynor, Jeffrey ; Tryphonopoulos, Panagiotis ; Kleiner, Gary I. ; Moon, Jang I. ; Nishida, Seigo ; Pappas, Peter A. ; Conanan, Lobella ; Weppler, Debbie ; Esquenazi, Violet ; Levi, David M. ; Kato, Tomoaki ; Tzakis, Andreas G. / Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation. In: Transplantation. 2007 ; Vol. 84, No. 9. pp. 1077-1081.
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abstract = "BACKGROUND. Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained. METHODS. Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient's DBS citrulline level. RESULTS. Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. ≥13 μmoles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4{\%} and >99{\%} respectively). Specificity was 54{\%} to 74{\%} in children and 83{\%} to 88{\%} in adults. CONCLUSIONS. Citrulline levels <13 μmoles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels ≥13μmoles/L practically rule out moderate or severe rejection.",
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T1 - Blood citrulline level is an exclusionary marker for significant acute rejection after intestinal transplantation

AU - David, Andre I.

AU - Selvaggi, Gennaro

AU - Ruiz, Phillip

AU - Gaynor, Jeffrey

AU - Tryphonopoulos, Panagiotis

AU - Kleiner, Gary I.

AU - Moon, Jang I.

AU - Nishida, Seigo

AU - Pappas, Peter A.

AU - Conanan, Lobella

AU - Weppler, Debbie

AU - Esquenazi, Violet

AU - Levi, David M.

AU - Kato, Tomoaki

AU - Tzakis, Andreas G.

PY - 2007/11/1

Y1 - 2007/11/1

N2 - BACKGROUND. Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained. METHODS. Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient's DBS citrulline level. RESULTS. Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. ≥13 μmoles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4% and >99% respectively). Specificity was 54% to 74% in children and 83% to 88% in adults. CONCLUSIONS. Citrulline levels <13 μmoles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels ≥13μmoles/L practically rule out moderate or severe rejection.

AB - BACKGROUND. Serum citrulline is a marker for acute cellular rejection (ACR) after intestinal transplantation; however, its clinical utility has not yet been established. The goal of this study was to determine clearcut serum levels beyond which the diagnosis of acute rejection could be supported or refuted, and predictors of citrulline levels posttransplant from which more accurate estimates of sensitivity and specificity could be obtained. METHODS. Since March 2004, we obtained 2135 dried blood spot (DBS) citrulline samples from 57 intestinal transplant recipients at or beyond 3 months posttransplant. Stepwise linear regression was performed to determine the most significant multivariable predictors of the patient's DBS citrulline level. RESULTS. Seven characteristics were associated with a significantly lower citrulline in multivariable analysis: presence of mild, moderate, or severe ACR; presence of bacteremia or respiratory infection; pediatric age; and time from transplant to DBS sample (P<0.00001 in each case). Using a <13 vs. ≥13 μmoles/L cutoff point, the sensitivity for detecting moderate or severe ACR and the negative predictive value were high (96.4% and >99% respectively). Specificity was 54% to 74% in children and 83% to 88% in adults. CONCLUSIONS. Citrulline levels <13 μmoles/L should alert the clinical team that a serious problem (rejection or infection) could be looming in a previously stable intestinal recipient. Levels ≥13μmoles/L practically rule out moderate or severe rejection.

KW - Acute cellular rejection

KW - Citrulline

KW - Dried blood spot

KW - Small intestine transplantation

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