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Relation of urinary gene expression of epithelial-mesenchymal transition markers with initial events and 1-year kidney graft function

Abstract: Introduction. Renal dysfunction due to acute rejection (AR), acute tubular necrosis, or calcineurin inhibitors toxicity is related to development of interstitial fibrosis/tubular atrophy (IF/TA) and graft survival. Determination of serum creatinine (sCr) displays poor sensitivity as a marker for early detection of graft dysfunction. Kidney biopsy is an accurate but invasive procedure for the diagnosis. The levels of urinary mRNA of genes that regulate epithelial-mesenchymal transition (EMT) can reflect early damage and detect the development of IF/TA. Repeated studies of these genes can provide noninvasive information about the evolution of the graft, facilitating early diagnosis and treatment. Objective. To analyze the relationships between early and 1-year graft evolution in relation to gene expression of EMT biomarkers. Methods. Seventy-one kidney transplant recipients were monitored during 1 year recording analytical, clinical, and histological (if available) data. We determined RNA gene expression of EMT, angiotensinogen, E-cadherin, N-cadherin, transforming growth factor (TGF) beta and bone morphogenetic patients 7 (BMP7). Results. At 3 months, angiotensinogen (mean [standard deviation]), (2.42 [.66] versus 8.58 [3.24]; P .017) and N-cadherin (0.59 [0.26] versus 3.15 [1.35]; P .016) discriminate a good evolution from AR episodes BMP-7 discriminated a good evolution versus AR (0.72 [0.29] versus 4.53 [2.23]; P .006) and delayed graft function versus AR (1.14 [0.79] versus 4.53 [2.23]; P .049). After 1 year, the ratio TGF-beta/BMP7 discriminated patients with an sCr 1.5 mg/dL (6614.6 [1063.6] versus 3378.7 [1019]; P .034). There was a positive correlation between urinary and tissue TGF-beta [r 59; P .003]. Conclusion. The expression of studied genes reverting EMT at 3 months postransplantation showed differences in initial graft evolution. At 1 year, the TGF-beta/BMP7 ratio suggested activation of EMT, possible early marker of renal dysfunction.

 Autoría: Gomez-Alamillo C., Ramos-Barron M., Benito-Hernandez A., Rodrigo E., Ruiz J., Agüeros C., Sanchez M., Arias M.,

 Fuente: Transplantation Proceedings, 2012, 44(9), 2573-2576

 Editorial: Elsevier

 Año de publicación: 2012

 Tipo de publicación: Artículo de Revista

 DOI: 10.1016/j.transproceed.2012.09.100

 ISSN: 0041-1345,1873-2623

 Url de la publicación: https://doi.org/10.1016/j.transproceed.2012.09.100