Evaluation of Gene Panel mRNAs in Urine Samples of Kidney Transplant Recipients as a Non-invasive Tool of Graft Function

Acute kidney injury (AKI) is a significant risk factor for developing chronic kidney disease and progression to end-stage renal disease in elderly patients. AKI is also a relatively common complication after kidney transplantation (KTx) associated with graft failure. Since the lifespan of a transplanted kidney is limited, the risk of the loss/deterioration of graft function (DoGF) should be estimated to apply the preventive treatment. The collection of saliva and urine is more convenient than collecting blood and can be performed at home. The study aimed to verify whether non-invasive biomarkers, determined in saliva and urine, may be useful in the prediction of DoGF in kidney transplant recipients (KTRs) (n = 92). Salivary and serum toxins (p-cresol sulfate, pCS; indoxyl sulfate, IS) concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Urinary proteins, hemoglobin, and glucose were measured using a semi-quantitative strip test. Salivary IS (odds ratio (OR) = 1.19), and proteinuria (OR = 3.69) were demonstrated as independent factors for the prediction of DoGF. Satisfactory discriminatory power (area under the receiver operating characteristic curve (AUC) = 0.71 ± 0.07) and calibration of the model were obtained. The model showed that categories of the increasing probability of the risk of DoGF are associated with the decreased risk of graft survival. The non-invasive diagnostic biomarkers are a useful screening tool to identify high-risk patients for DoGF.

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Micro RNA 146a-5p expression in Kidney transplant recipients with delayed graft function

Brazilian Journal of Nephrology ◽

10.1590/2175-8239-jbn-2018-0098 ◽

2019 ◽

Vol 41 (2) ◽

pp. 242-251 ◽

Cited By ~ 5

Author(s):

Patricia Milhoransa ◽

Carolina Caruccio Montanari ◽

Rosangela Montenegro ◽

Roberto Ceratti Manfro

Keyword(s):

Kidney Transplant ◽

Peripheral Blood ◽

Graft Function ◽

Renal Tissue ◽

Delayed Graft Function ◽

Kidney Graft ◽

Transplant Recipients ◽

Graft Dysfunction ◽

Kidney Transplant Recipients ◽

Non Invasive

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.

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Associations of pre-transplant anemia management with post-transplant delayed graft function in kidney transplant recipients

Clinical Transplantation ◽

10.1111/j.1399-0012.2012.01598.x ◽

2012 ◽

Vol 26 (5) ◽

pp. 782-791 ◽

Cited By ~ 3

Author(s):

Miklos Z. Molnar ◽

Csaba P. Kovesdy ◽

Laszlo Rosivall ◽

Suphamai Bunnapradist ◽

Junichi Hoshino ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Delayed Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Anemia Management

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Prevalence and risk factors for death with graft function among Egyptian kidney transplant recipients in Mansoura

Zagazig University Medical Journal ◽

10.21608/zumj.2021.55359.2074 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

mostafa abu gharbia ◽

ahmed salah ◽

Yaser Elhendy ◽

Ayman refaie

Keyword(s):

Risk Factors ◽

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Association of Factor V Leiden Mutation with Delayed Graft Function, Acute Rejection Episodes and Long-term Graft Dysfunction in Kidney Transplant Recipients

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612972 ◽

2002 ◽

Vol 87 (02) ◽

pp. 194-198 ◽

Cited By ~ 32

Author(s):

Torsten Slowinski ◽

Ingeborg Hauser ◽

Birgit Vetter ◽

Lutz Fritsche ◽

Daniela Bachert ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Graft Function ◽

Factor V Leiden ◽

Factor V ◽

Transplant Recipients ◽

Graft Dysfunction ◽

Kidney Transplant Recipients ◽

Factor V Leiden Mutation

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.

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A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

Frontiers in Medicine ◽

10.3389/fmed.2020.634260 ◽

2021 ◽

Vol 7 ◽

Author(s):

Rainer Oberbauer ◽

Matthias Edinger ◽

Gabriela Berlakovich ◽

Peter Kalhs ◽

Nina Worel ◽

...

Keyword(s):

Bone Marrow ◽

Kidney Transplant ◽

Graft Function ◽

Control Group ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Post Transplant ◽

Donor Bone Marrow ◽

Living Donor Kidney Transplant

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR <35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.

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Long-Term Care of the Pediatric Kidney Transplant Recipient

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.16891020 ◽

2021 ◽

pp. CJN.16891020

Author(s):

Hilda E. Fernandez ◽

Bethany J. Foster

Keyword(s):

Transplant Recipient ◽

Kidney Transplant ◽

Graft Failure ◽

Graft Function ◽

Failure Rates ◽

Care Providers ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Term Care

Pediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize transition to adult-oriented transplant care and long-term outcomes.

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