Publications (2)2.01 Total impact
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Article: Relation of urinary gene expression of epithelial-mesenchymal transition markers with initial events and 1-year kidney graft function.
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ABSTRACT: 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. To analyze the relationships between early and 1-year graft evolution in relation to gene expression of EMT biomarkers. 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). 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]. 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.Transplantation Proceedings 11/2012; 44(9):2573-6. · 1.00 Impact Factor -
Article: Analysis of urinary gene expression of epithelial-mesenchymal transition markers in kidney transplant recipients.
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ABSTRACT: Renal graft dysfunction due to acute rejection, acute tubular necrosis, or anticalcineurin toxicity with development of interstitial fibrosis or tubular atrophy are the primary causes of graft failure. Determination of kidney function using the serum creatinine concentration demonstrates low sensitivity as a marker for the diagnosis, and kidney biopsy is an invasive procedure. The levels of urinary messenger RNA of genes that regulate epithelial-mesenchymal transition (EMT) can reflect early kidney damage. Thus, repeated transcriptome studies of these genes can provide information about the evolution of the graft, and possibly enable early diagnosis and treatment. To analyze the temporal relationships between early graft evolution and gene expression of EMT biomarkers. Of 70 kidney transplant procedures performed between January 1, 2007 and December 31, 2008, 42 were analyzed prospectively for 3 months. Analytical and clinical data were recorded, as well as histologic findings if available. Urine mRNA extraction was performed using a commercially available kit. RNA gene expression of EMT, angiotensinogen, epidermal growth factor receptor, E-cadherin, N-cadherin, transforming growth factor-β, and bone morphogenetic protein 7 was determined at real-time quantitative polymerase chain reaction. β2-Microglobulin was used as a reference gene. At 75 days posttransplantation, analysis revealed that angiotensinogen (mean [SD], 2.91 [0.70] vs 6.04 [1.24]; P=.04) and N-cadherin (1.01 [0.43] vs 4.31 [0.92]; P=.01) discriminate good evolution from acute rejection. Epidermal growth factor receptor (2.78 [0.66] vs 6.02 [1.09]; P=.33) and bone morphogenetic protein 7 (0.85 [0.33] vs 3.07 [1.37]; P=.04) discriminate good evolution vs delayed graft function. Differential gene expression at 75 days posttransplantation reflects differences related to initial histologic damage. This observation encourages design of a long-term longitudinal analysis with multiple markers to obtain early diagnosis and forecast the prognosis of graft dysfunction.Transplantation Proceedings 10/2010; 42(8):2886-8. · 1.00 Impact Factor
