Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients

Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography–mass spectrometry (GC-MS). Focused metabolite panels were identified that could detect biopsy confirmed acute rejection with 92.9% sensitivity and 96.3% specificity (11 metabolites) and could differentiate BK viral nephritis (BKVN) from acute rejection with 88.9% sensitivity and 94.8% specificity (4 metabolites). Overall, targeted metabolomic analyses of biopsy-matched urine samples enabled the generation of refined metabolite panels that non-invasively detect graft injury phenotypes with high confidence. These urine biomarkers can be rapidly assessed for non-invasive diagnosis of specific transplant injuries, opening the window for precision transplant medicine.

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Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients, part II: omics analyses of urine and blood samples

Clinical Kidney Journal ◽

10.1093/ckj/sfw077 ◽

2016 ◽

pp. sfw077 ◽

Cited By ~ 5

Author(s):

Pauline Erpicum ◽

Oriane Hanssen ◽

Laurent Weekers ◽

Pierre Lovinfosse ◽

Paul Meunier ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Blood Samples ◽

Non Invasive

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FP699URINARY EXOSOMAL MICRORNA AS A NON-INVASIVE BIOMARKER FOR THE DIAGNOSIS OF ACUTE REJECTION IN KIDNEY TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfy104.fp699 ◽

2018 ◽

Vol 33 (suppl_1) ◽

pp. i281-i281

Author(s):

Won Hee Cho ◽

Yu Ho Lee ◽

Young Hee Kim ◽

Su-Woong Jung ◽

Yang-Gyun Kim ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Non Invasive ◽

Exosomal Microrna

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Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients. Part I.In vivoimaging methods

Clinical Kidney Journal ◽

10.1093/ckj/sfw062 ◽

2016 ◽

pp. sfw062 ◽

Cited By ~ 4

Author(s):

Oriane Hanssen ◽

Pauline Erpicum ◽

Pierre Lovinfosse ◽

Paul Meunier ◽

Laurent Weekers ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Non Invasive

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

Molecular Medicine ◽

10.2119/2007-00017.mas ◽

2007 ◽

Vol 13 (5-6) ◽

pp. 315-324 ◽

Cited By ~ 21

Author(s):

Valeria R Mas ◽

Luciana A Mas ◽

Kellie J Archer ◽

Kenneth Yanek ◽

Anne L King ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Gene Panel ◽

Urine Samples ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Non Invasive

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Immune Monitoring in Kidney Transplant Recipients Could Predict Acute Rejection by a New Method: Flow Cytometric Microcarrier Assay

Transplantation Proceedings ◽

10.1016/j.transproceed.2013.01.018 ◽

2013 ◽

Vol 45 (4) ◽

pp. 1508-1510 ◽

Cited By ~ 1

Author(s):

Z.-K. Jin ◽

C.-X. Xu ◽

P.-X. Tian ◽

W.-J. Xue ◽

T.-C. Mao ◽

...

Keyword(s):

Acute Rejection ◽

Kidney Transplant ◽

Immune Monitoring ◽

New Method ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Flow Cytometric

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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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Correlations of Serum and Urine Levels of Neopterin, IL-8, IL-6, IL-6R, Basic Fetoprotein and Hepatocytes Growth Factor with Acute Rejection in kidney Transplantation

Pteridines ◽

10.1515/pteridines.1998.9.1.22 ◽

1998 ◽

Vol 9 (1) ◽

pp. 22-25

Author(s):

Tsuneharu Miki ◽

Shiro Takahara ◽

Akihiko Okuyma

Keyword(s):

Acute Rejection ◽

Rejection Episode ◽

Stable Condition ◽

Serum Levels ◽

Acute Rejection Episode ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Urinary Neopterin ◽

Basic Fetoprotein ◽

Urine Levels

Summary Levels of serum- and urinary-neopterin and serum-IL-6 and IL-6R of kidney transplant recipients "Were higher in acute rejection episode than in stable condition. IL-8 serum levels had risen prior to clinical diagnosis of acute rejection episode. Serum HGF levels also increased during acute rejection episode to over 1 ng/ml. Serum-neopterin and IL-6R levels were relatively sensitive for the detection of acute rejection episode.

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Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

F1000Research ◽

10.12688/f1000research.10414.1 ◽

2016 ◽

Vol 5 ◽

pp. 2893 ◽

Cited By ~ 15

Author(s):

Rossana Rosa ◽

Jose F. Suarez ◽

Marco A. Lorio ◽

Michele I. Morris ◽

Lilian M. Abbo ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Acute Rejection ◽

Clinical Outcomes ◽

Kidney Transplant ◽

Graft Survival ◽

Patient Survival ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Serious Infections ◽

The Impact

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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