Abstract
A biochemical marker for detection of acute cellular rejection following small intestine transplantation has been sought. Citrulline, a non- protein amino acid synthesized mainly by functioning enterocytes, has been proposed. Trial sensitivity has been reportedly high but with low specificity. Thus, the goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection. Since March, 2004 2,135 dried blood spot (DBS) citrulline samples were obtained from 57 small intestine transplant recipients three months or more after post-transplant, i.e., once the expected period of recovery in the citrulline levels had occurred. Using a <13 vs. > 13 micromoles/L cut off point, sensitivity of DBS citrulline for the detection of moderate or severe ACR was extremely high (96.4%). Furthermore, specificity estimates (given the absence of ACR and these particular infections), while controlling for time-to-DBS sample were reasonably high (54%-74% in children and 83%-88% in adults), and the negative predictive value (NPV) was >99%. Citrulline is a non-invasive marker to evaluate problems of the intestinal graft after three months post-transplant. Due to the high NPV, a moderate or severe ACR can be ruled out, based exclusively on knowledge of a high value for DBS citrulline.
Highlights
Specificity estimates, while controlling for time-to-DBS sample were reasonably high (54%-74% in children and 83%-88% in adults), and the negative predictive value (NPV) was >99%
The goal was to determine, in a sufficiently large analysis, the significant value of citrulline level in the post-transplant setting, which would correlate with complications such as rejection and infection
Yu HC, Tuteja S, Moon JI, Kleiner GI, Conanan L, Gaynor JJ, et al Utilization of dried blood spot citrulline level as a noninvasive method for monitoring graft function following intestinal transplantation
Summary
VALOR CRÍTICO DA CITRULINA PARA AS COMPLICAÇÕES DO ENXERTO NO TRANSPLANTE DE INTESTINO. O uso da citrulina tem sido proposto também como um simples marcador quantitativo da lesão do epitélio intestinal após radioterapia e mielossupressão[16,19] Tzakis et al compararam os valores da citrulina entre doentes pré-transplante e voluntários saudáveis, sendo que os níveis dos primeiros foram significativamente menores. Foi relatado por Pappas et al.[21], que ocorre um atraso na normalização dos valores da citrulina naqueles receptores de TI que apresentaram episódios de RCA nos primeiros meses após o transplante. Tanto em crianças como em adultos, o VPN é >99% quando o valor de corte de 13 μmoles/L foi utilizado nos períodos de RCA moderada ou grave. Tabela 1 - Estimativas dos valores preditivos positivos (VPP) e negativos (VPN) de valores de corte entre 10 a 15 μmoles/L da citrulina para detectar RCA moderada ou grave (Universidade de Miami, Jackson Memorial Hospital, 2006)
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