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• W2775803578 abstract "Molecular biomarkers in blood and urine samples could help risk stratify kidney transplant recipients (KTR) and reduce the need for invasive testing with biopsies to diagnose acute rejection (AR). Changes at molecular level are likely to precede both histological findings and graft dysfunction, allowing earlier diagnosis and treatment to limit graft damage. The aim of our study is to identify and characterize biomarkers that can diagnose and predict AR in KTR. Blood and urine samples were collected from KTR before the transplant and over the first year post-transplant at 26 time-points and during episodes of graft dysfunction. RNA was extracted from blood collected into Tempus Blood RNA tubes and from urine sediment cells. cDNA was synthesised and pre-amplified for urine. Quantitative real time PCR was done for 20(blood) or 23(urine) target and 4 control genes. A pilot study consisting of 18 biopsy proven acute rejection (BPAR) and 26 stable KTR revealed a significant over-expression of 5 genes in blood (SEMA7A, PF4, TGFB, ITGAM, C6orf25) at week 2 post transplantation in the BPAR group, thereby predicting the subsequent development of rejection episodes occurring up to one year post-transplantation (Wilcoxon test, p<0.05, FDR <5%). Using the expression of these 5 genes in a multivariate prediction model returned a probability score that predicted BPAR with a sensitivity of 0.7, specificity of 0.95, and an AUC of 0.80. Rise in SEMA7A, TGFB and IP-10 gene expression in blood of BPAR occurred 3-4 weeks prior to biopsy compared to creatinine rise that was 1 week pre-biopsy. For urine, the difference of gene expression 1-2 weeks and 3-4 weeks pre-biopsy was analysed in 14 BPAR and 14 stable samples at matched time points. Difference in Perforin, PDCD1, FasL and IP-10 expression were detected between these groups. Thus it might be possible to use a urine test to predict a rejection episode with high specificity and sensitivity up to 4 weeks before it occurs. Our pilot study suggests that mRNA levels in blood and urine could help risk-stratify patients for AR in KTR before clinical evidence of AR allowing better management and potential individualisation of anti-rejection therapy. Validation of these findings in a larger cohort is clearly needed." @default.
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• W2775803578 date "2014-07-01" @default.
• W2775803578 modified "2023-09-27" @default.
• W2775803578 title "Non-Invasive Tests to Help Stratify Risk of Rejection in Renal Transplant Recipients." @default.
• W2775803578 doi "https://doi.org/10.1097/00007890-201407151-02998" @default.
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