Original Article

Kidney International (2008) 73, 877–884; doi:10.1038/sj.ki.5002795; published online 23 January 2008

Non-invasive diagnosis of acute rejection in kidney transplants with delayed graft function

E C Aquino-Dias1, G Joelsons2, D M da Silva2, R H Berdichewski2, A R Ribeiro2, F J V Veronose1,2, L F Gonçalves1,2 and R C Manfro1,2

  1. 1Post-Graduate Medical Sciences—Nephrology Program, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  2. 2Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

Correspondence: RC Manfro, Division of Nephrology, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, Room 2030, Porto Alegre, RS 90035-003, Brazil. E-mail: rmanfro@hcpa.ufrgs.br

Received 11 April 2007; Revised 30 October 2007; Accepted 13 November 2007; Published online 23 January 2008.

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Abstract

Delayed graft function (DGF) often occurs in kidney transplants from deceased donors. We wanted to provide studies giving more accurate non-invasive tests for acute rejection (AR). Using real-time PCR, we examined the expression of cytolytic molecules such as perforin, granzyme B, and fas-ligand along with serpin proteinase inhibitor-9. We also measured the expression of FOXP3, a characteristic gene of T-regulatory cells known to be involved in AR. These studies were conducted on peripheral blood monocytes, urinary cells, and 48 surveillance kidney biopsies taken from a total of 35 patients with DGF. Of these patients, 20 had a histopathological diagnosis of AR, whereas other 28 had characteristics of acute tubular necrosis (ATN). Expression of cytolytic and apoptotic-associated genes in the biopsy tissue, peripheral blood leukocytes, and urinary cells was significantly higher in patients with AR than that in patients with ATN. Diagnostic parameters associated with FOXP3 gene expression were most accurate in peripheral blood leukocytes and urine cells with sensitivity, specificity, positive and negative predictive values, and accuracy between 94 and 100%. Our study shows that quantification of selected genes in peripheral blood leukocytes and urinary cells from renal transplant patients with DGF may provide a useful and accurate non-invasive diagnosis of AR.

Keywords:

kidney transplantation, perforin, fas-ligand, FOXP3, delayed graft function, acute rejection

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