RESUMEN
BACKGROUND: Kidney graft fibrosis is a major factor related to chronic loss of kidney function. At present, the finding of fibrosis depends on the analysis of tissue in the renal biopsy, which has important limitations. In this study, we evaluated the messenger mRNA transcription and gene expression of kidney injury molecule-1 (KIM-1) in kidney tissue and in urinary sediment cells of kidney transplant patients with graft dysfunction aiming at the development of techniques that may allow the noninvasive diagnosis of interstitral fibrosis/tubular atrophy (IF/TA). PATIENTS AND METHODS: RNA extracted from cells in tissue and urine of 77 renal transplant patients whose biopsies were classified according to the Banff scheme-2007. Four diagnostic groups were established: (1) acute tubular necrosis (n = 9); (2) acute rejection (n = 49); (3) acute calcineurin inhibitors nephrotoxicity (n = 10); and (4) interstitial fibrosis and tubular atrophy (IFTA, n = 29). Tissue and urine cell RNA was amplified and quantification were made by real-time polymerase chain reactron. Data from the quantification of gene expression are presented as median and 25th to 75th percentiles. RESULTS: Messenger RNA levels of the KIM-1 gene were higher in the biopsies (26.17; 3.38-294.53) and urinary sediment cells (0.09; 0-5.81) of the patients classified as having IF/TA as compared with all others groups. A significant correlation between gene expression in samples of urine and tissue cells was found (P < .01). CONCLUSION: These initial data suggests that KIM-1 gene mRNA quantification can be used as a noninvasive biomarker of IF/TA.
Asunto(s)
Rechazo de Injerto/genética , Enfermedades Renales/genética , Trasplante de Riñón/efectos adversos , Riñón/química , Riñón/cirugía , Glicoproteínas de Membrana/genética , ARN Mensajero/análisis , Receptores Virales/genética , Atrofia , Biopsia , Femenino , Fibrosis , Marcadores Genéticos , Rechazo de Injerto/patología , Rechazo de Injerto/orina , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Inmunosupresores/efectos adversos , Riñón/efectos de los fármacos , Riñón/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Enfermedades Renales/orina , Masculino , Glicoproteínas de Membrana/orina , Necrosis , Valor Predictivo de las Pruebas , ARN Mensajero/orina , Reacción en Cadena en Tiempo Real de la Polimerasa , Resultado del Tratamiento , UrinálisisRESUMEN
BACKGROUND: Kidney injury molecule-1 (KIM-1), a type I transmembrane protein that is not expressed in normal renal tissue, shows increased expression in dedifferentiated cells within damaged regions of the proximal tubule. We evaluated mRNA transcription of the KIM-1 gene in renal tissue of kidney transplant patients who were experiencing graft dysfunction searching for an accurate biomarker of kidney graft injury. PATIENTS AND METHODS: mRNA analysis was performed on 59 biopsies from kidney transplant patients who had been classified according to the Banff 1997 scheme. Biopsies were categorized in 5 diagnostic groups: acute tubular necrosis (ATN) with superimposed acute rejection episode (ARE), ATN; ARE; calcineurin inhibitor nephrotoxicity (CIN); or interstitial fibrosis and tubular atrophy (IFTA). Amplified tissue RNA was quantified by real-time polymerase chain reaction. RESULTS: Renal tissue evaluations showed significantly increased KIM-1 mRNA expression as shown by median values, 25-75 percentiles, and averages of the logarithmic transformation: namely, CIN group (50.6; 1.8-285, 1; 1.24) and IFTA group (7.5; 1.26-14.6; 0.62), displayed significant differences (P > .05). In contrast, expression was lower among the ATN (0.47; 0.28-1.06; -0.13); ARE (0.21; 0.11-0.78; -0.45), and ATN+ARE (0.46; 0.06-3.27; -0.25) cohorts. CONCLUSION: These preliminary data suggested that KIM-1 mRNA might be useful biomarker of tubular damage associated with CIN and IFTA.
