Arah Lee1, Jong-Cheol Jeong, Young-Wook Choi, Hwa-Young Seok, Yang-Gyun Kim, Kyung-Hwan Jeong, Ju-Young Moon, Tae-Won Lee, Chun-Gyoo Ihm, Hee Jung Jeon, Tai-Yeon Koo, Curie Ahn, Sung-Jig Lim, Jaeseok Yang, Sang-Ho Lee. 1. 1 Division of Nephrology, Department of Internal Medicine, College of Medicine, Kyung Hee University, Seoul, South Korea. 2 Transplantation Center, Seoul National University Hospital, Seoul, South Korea. 3 Transplantation Research Institute, Seoul National University College of Medicine, Seoul, South Korea. 4 Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 5 Department of Pathology, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, South Korea. 6 Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, South Korea. 7 Address correspondence to: Jaeseok Yang, M.D., Ph.D., or Sang-Ho Lee, M.D., Ph.D., Department of Nephrology, Kyung Hee University, 149 Sangil-Dong, Gangdong-Gu, Seoul, 134-702, South Korea.
Abstract
BACKGROUND: Diagnosing acute rejection (AR) in kidney transplant recipients typically requires an invasive kidney biopsy. A previous study has suggested that expression of five genes in peripheral blood can indicate the presence of AR in American pediatric kidney transplant recipients. This study aims to validate if these five genes are also useful to diagnose AR in Korean adult kidney transplant patients. METHODS: Blood samples were collected from 143 patients (39 biopsy-proven AR, 84 stable patients, and 20 other graft injuries) at an average of 9 months posttransplantation and performed real-time PCR for five-gene biomarkers (DUSP1, NKTR, MAPK9, PSEN1, and PBEF1). RESULTS: Patients with acute cellular rejection (ACR) had a significantly decreased level of MAPK9 and a significantly increased level of PSEN1 when compared with controls and also with patients with other graft injury (OGI). In multivariate logistic regression analysis, for discrimination between ACR and OGI, an excellent diagnostic accuracy was observed in the gene sets but five-gene set generated a higher AUC than two-gene set. With clinical variables combined to these gene sets, the diagnostic accuracy increased in both five-gene set and two-gene set. CONCLUSIONS: These results support the validity of 5 gene-set for the prediction of AR in Asian adult kidney transplant recipients and suggest the promising role of the peripheral blood gene test in the diagnosis of AR in kidney transplantation.
BACKGROUND: Diagnosing acute rejection (AR) in kidney transplant recipients typically requires an invasive kidney biopsy. A previous study has suggested that expression of five genes in peripheral blood can indicate the presence of AR in American pediatric kidney transplant recipients. This study aims to validate if these five genes are also useful to diagnose AR in Korean adult kidney transplant patients. METHODS: Blood samples were collected from 143 patients (39 biopsy-proven AR, 84 stable patients, and 20 other graft injuries) at an average of 9 months posttransplantation and performed real-time PCR for five-gene biomarkers (DUSP1, NKTR, MAPK9, PSEN1, and PBEF1). RESULTS:Patients with acute cellular rejection (ACR) had a significantly decreased level of MAPK9 and a significantly increased level of PSEN1 when compared with controls and also with patients with other graft injury (OGI). In multivariate logistic regression analysis, for discrimination between ACR and OGI, an excellent diagnostic accuracy was observed in the gene sets but five-gene set generated a higher AUC than two-gene set. With clinical variables combined to these gene sets, the diagnostic accuracy increased in both five-gene set and two-gene set. CONCLUSIONS: These results support the validity of 5 gene-set for the prediction of AR in Asian adult kidney transplant recipients and suggest the promising role of the peripheral blood gene test in the diagnosis of AR in kidney transplantation.