Micro RNA142-3p Is Differentially Expressed in the Peripheral Blood of Kidney Transplant Recipients With Graft Dysfunction Without Acute Rejection.

2014 ◽  
Vol 98 ◽  
pp. 464
Author(s):  
T. Domenico ◽  
G. Joelsons ◽  
F. Spuldaro ◽  
R. Montenegro ◽  
L. Goncalves ◽  
...  
2002 ◽  
Vol 87 (02) ◽  
pp. 194-198 ◽  
Author(s):  
Torsten Slowinski ◽  
Ingeborg Hauser ◽  
Birgit Vetter ◽  
Lutz Fritsche ◽  
Daniela Bachert ◽  
...  

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.


2019 ◽  
Vol 30 (8) ◽  
pp. 1481-1494 ◽  
Author(s):  
Weijia Zhang ◽  
Zhengzi Yi ◽  
Karen L. Keung ◽  
Huimin Shang ◽  
Chengguo Wei ◽  
...  

BackgroundIn kidney transplant recipients, surveillance biopsies can reveal, despite stable graft function, histologic features of acute rejection and borderline changes that are associated with undesirable graft outcomes. Noninvasive biomarkers of subclinical acute rejection are needed to avoid the risks and costs associated with repeated biopsies.MethodsWe examined subclinical histologic and functional changes in kidney transplant recipients from the prospective Genomics of Chronic Allograft Rejection (GoCAR) study who underwent surveillance biopsies over 2 years, identifying those with subclinical or borderline acute cellular rejection (ACR) at 3 months (ACR-3) post-transplant. We performed RNA sequencing on whole blood collected from 88 individuals at the time of 3-month surveillance biopsy to identify transcripts associated with ACR-3, developed a novel sequencing-based targeted expression assay, and validated this gene signature in an independent cohort.ResultsStudy participants with ACR-3 had significantly higher risk than those without ACR-3 of subsequent clinical acute rejection at 12 and 24 months, faster decline in graft function, and decreased graft survival in adjusted Cox analysis. We identified a 17-gene signature in peripheral blood that accurately diagnosed ACR-3, and validated it using microarray expression profiles of blood samples from 65 transplant recipients in the GoCAR cohort and three public microarray datasets. In an independent cohort of 110 transplant recipients, tests of the targeted expression assay on the basis of the 17-gene set showed that it identified individuals at higher risk of ongoing acute rejection and future graft loss.ConclusionsOur targeted expression assay enabled noninvasive diagnosis of subclinical acute rejection and inflammation in the graft and may represent a useful tool to risk-stratify kidney transplant recipients.


2018 ◽  
Vol 28 (2) ◽  
pp. 134-141 ◽  
Author(s):  
Mehri Barabadi ◽  
Sanaz Keshavarz Shahbaz ◽  
Farshad Foroughi ◽  
Morteza Hosseinzadeh ◽  
Mohsen Nafar ◽  
...  

Background: Diagnosis of allograft dysfunction by noninvasive biomarker tests is preferable to invasive allograft biopsies and has been extensively considered in recent years. This study aims to evaluate blood and urinary forkhead box P3 (FOXP3) messenger RNA (mRNA) expression in renal transplant recipients in an attempt to determine whether differential diagnosis of graft dysfunction is feasible using mRNA profiles. Methods: We analyzed FOXP3 mRNA expression in paired urinary and peripheral blood mononuclear cell (PBMC) samples. A total of 91 kidney transplant recipients enrolled in this study that were classified into 3 groups: biopsy-proven acute rejection (AR; n = 27), chronic allograft nephropathy (n = 19), and well-functioning graft (n = 45). The FOXP3 mRNA expression was quantified by TaqMan probe real-time polymerase chain reaction. Results: Acute rejection patients had a higher expression level of transcription factor FOXP3 compared to the chronic nephropathy and control groups. Analysis of receiver operating characteristic curves showed that rejection could be diagnosed with 100% sensitivity and 96% specificity in urine, and 92% sensitivity and 86% specificity in PBMC samples using the optimal FOXP3 mRNA cutoff value. We subdivided the AR group into progressive and nonprogressive patients, which showed a significant difference in FOXP3 mRNA expression. This result confirmed the role of FOXP3 as a diagnostic marker in predicting transplantation outcomes. Conclusion: Our results suggested that elevated expression of FOXP3 in blood and urine samples from kidney transplant recipients could be a useful noninvasive biomarker to diagnose graft dysfunction.


2018 ◽  
Vol 102 ◽  
pp. S180 ◽  
Author(s):  
Maria Hernandez-Fuentes ◽  
Sofia Christakoudi ◽  
Manohursingh Runglall ◽  
Paula Mobillo ◽  
Tjir-Li Tsui ◽  
...  

2019 ◽  
Vol 41 (2) ◽  
pp. 242-251 ◽  
Author(s):  
Patricia Milhoransa ◽  
Carolina Caruccio Montanari ◽  
Rosangela Montenegro ◽  
Roberto Ceratti Manfro

ABSTRACT Introduction: The development of novel non-invasive biomarkers of kidney graft dysfunction, especially in the course of the delayed graft function period would be an important step forward in the clinical practice of kidney transplantation. Methods: We evaluated by RT-PCR the expression of miRNA-146 to -5p ribonucleic micro-acids (miRNAs) in the peripheral blood and renal tissue obtained from kidney transplant recipients who underwent a surveillance graft biopsy during the period of delayed graft function. Results: In biopsy samples, the expression of miR-146a-5p was significantly increased in the group of patients with delayed graft function (DGF) (n = 33) versus stables patients (STA) (n = 13) and patients with acute rejection (AR) (n = 9) (p = 0.008). In peripheral blood samples, a non-significant increase of miR-146a-5p expression was found in the DGF group versus STA and AR groups (p = 0.083). No significant correlation was found between levels of expression in biopsy and plasma. ROC curve analysis revealed an AUC of 0.75 (95% CI: 0.62-0.88) for the renal tissue expression and 0.67 (95% CI 0.52-0.81) for the peripheral blood expression. Conclusion: We conclude that miR-146a-5p expression has a distinct pattern in the renal tissue and perhaps in the peripheral blood in the setting of DGF. Further refinements and strategies for studies should be developed in the field of non-invasive molecular diagnosis of kidney graft dysfunction.


2018 ◽  
Vol 35 (5) ◽  
pp. 474-480
Author(s):  
Agnieszka Cegielska ◽  
Katarzyna Lisowska ◽  
Alicja Dębska-Ślizień ◽  
Beata Imko-Walczuk ◽  
Aleksandra Okuniewska ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2893 ◽  
Author(s):  
Rossana Rosa ◽  
Jose F. Suarez ◽  
Marco A. Lorio ◽  
Michele I. Morris ◽  
Lilian M. Abbo ◽  
...  

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients.  We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV+ kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV- to HIV+ adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation.  The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% (p=0.06) and 82% vs. 100% (p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02).  Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV+ kidney transplant recipients.


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