RESUMO
BACKGROUND: Gene expression analysis of fibrosis-related genes may became useful for the early identification of fibrosis processes. We quantitatively assessed messenger RNA transcripts of the CTGF, TGF-ß and KIM-1 genes, in biopsy samples from renal transplant recipients with graft dysfunction, to test the hypothesis that in patients with chronic disease of the renal transplant, these molecules could be markers of the development and severity of graft fibrosis. METHODS: Ninety-six kidney transplant recipients who undertook 121 indication graft biopsies between January 2008 and December 2009 were included. Patients and biopsies were classified into 4 major diagnostic groups according to the Banff 2007 classification: acute tubular necrosis (ATN; n = 20), acute rejection (AR; n = 58), acute calcineurin inhibitor nephrotoxicity (CIN; n = 13) and interstitial fibrosis and tubular atrophy (IF/TA; n = 30). RESULTS: Messenger RNA transcripts of the CTGF and TGF-ß genes were significantly higher in IF/TA compared with all other conditions. Messenger RNA transcripts of the KIM-1 gene in the IF/TA group were higher than in the CIN group. In addition, it was observed that gene expression of CTGF, TGF-ß and KIM-1 increased with severity of fibrosis observed in the pathological examinations. CONCLUSIONS: Gene expression evaluation of the kidney graft tissue may be used to improve pathological diagnosis and perhaps for the future development of noninvasive biomarkers.
Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , Expressão Gênica , Rejeição de Enxerto/genética , Transplante de Rim , Rim/patologia , Glicoproteínas de Membrana/genética , RNA Mensageiro/metabolismo , Receptores Virais/genética , Fator de Crescimento Transformador beta/genética , Adulto , Idoso , Aloenxertos , Atrofia/genética , Biópsia , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Feminino , Fibrose/genética , Rejeição de Enxerto/patologia , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Rim/metabolismo , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Fator de Crescimento Transformador beta/metabolismoRESUMO
BACKGROUND: Renal biopsies are usually needed to elucidate graft dysfunction. In this study, T-cell immunoglobulin domain, mucin domain mRNA expression in the peripheral blood leukocytes (PBL) and urinary cells (UC) were studied as a noninvasive method for the diagnosis of acute rejection (AR) of kidney transplant patients with dysfunction. METHODS: One hundred sixty biopsies were obtained from 115 patients. Blood and urine samples were collected immediately before the biopsies. Histopathologic diagnoses were acute tubular necrosis with superimposed AR or acute tubular necrosis in patients with delayed graft function (DGF), and (AR), or calcineurin inhibitor nephrotoxicity (CIN), or interstitial fibrosis and tubular atrophy in patients with acute graft dysfunction (AGD). Fifteen protocol biopsies of stable grafts were used as controls. mRNA relative quantification was performed by real-time polymerase chain reaction. RESULTS: Gene expression in tissue, PBL, and UC was always higher in patients with AR than in patients with the other causes of graft dysfunction (P<0.001). Significant correlations of gene expression in different compartments were observed (P<0.001). The obtained diagnostic parameters were 100% accurate in the DGF group and, respectively, for blood and urine: sensitivity (87% and 84%); specificity (95% and 96%); positive predictive value (87% and 89%); negative predictive value (93% and 94%); and accuracy (91% and 93%) for the group of patients with AGD. CONCLUSION: T-cell immunoglobulin domain, mucin domain mRNA quantification by real-time polymerase chain reaction in PBL and UC of renal transplant patients undergoing DGF or AGD may become a useful tool for an accurate noninvasive diagnosis of AR.
