Urinary mitochondrial DNA associates with delayed graft function following renal transplantation

2018 ◽  
Vol 35 (8) ◽  
pp. 1320-1327 ◽  
Author(s):  
Marcel P B Jansen ◽  
Wilco P C Pulskens ◽  
Melissa Uil ◽  
Nike Claessen ◽  
Gerrie Nieuwenhuizen ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Renal Transplantation ◽  
Nicotinamide Adenine Dinucleotide ◽  
Nuclear Dna ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Nicotinamide Adenine ◽  
Renal Transplant Recipients ◽  
Ischaemia Time ◽  
Allograft Function

Abstract Background Ischaemia-reperfusion (IR) injury is an important determinant of delayed graft function (DGF) affecting allograft function. Mitochondrial DNA (mtDNA) is released upon cell death and platelet activation into the extracellular environment and has been suggested to be a biomarker in several diseases. Whether extracellular mtDNA accumulates in plasma and/or urine upon renal IR and predisposes DGF is unknown. Methods C57BL/6J wild-type mice were subjected to renal IR. In addition, an observational case–control study was set up enrolling 43 patients who underwent kidney transplantation. One day post-IR in mice and a few days following renal transplantation in human, blood and urine were collected. Patients were stratified into DGF and non-DGF groups. Results mtDNA-encoded genes accumulate in urine and plasma in both mice subjected to renal IR injury and in humans following renal transplantation. In human renal transplant recipients, cold ischaemia time and renal function correlate with urinary mtDNA levels. Urinary mtDNA levels but not urinary nuclear DNA levels were significantly higher in the DGF group compared with the non-DGF group. Multiple receiver operating characteristic curves revealed significant diagnostic performance for mtDNA-encoded genes cytochrome c oxidase III (COXIII); nicotinamide adenine dinucleotide hydrogen subunit 1 (NADH-deh); mitochondrially encoded, mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 2 (MT-ND2) with an area under the curve of, respectively, 0.71 [P = 0.03; 95% confidence interval (CI) 0.54–0.89], 0.75 (P = 0.01; 95% CI 0.58–0.91) and 0.74 (P = 0.02; 95% CI 0.58–0.89). Conclusions These data suggest that renal ischaemia time determines the level of mtDNA accumulation in urine, which associates with renal allograft function and the diagnosis of DGF following renal transplantation.

scholarly journals Prediction of delayed graft function after renal transplantation

2013 ◽  
Vol 3 (5) ◽  
pp. 377 ◽  
Author(s):  
Claudio Jeldres ◽  
Héloïse Cardinal ◽  
Alain Duclos ◽  
Shahrokh F. Shariat ◽  
Nazareno Suardi ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Function ◽  
Area Under The Curve ◽  
Delayed Graft Function ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Donor Age ◽  
Hla Dr ◽  
Recipient Age ◽  
User Friendly

Introduction: Delayed graft function (DGF), defined as the needfor dialysis during the first week after renal transplantation, is animportant adverse clinical outcome. A previous model relied on16 variables to quantify the risk of DGF, thereby undermining itsclinical usefulness. We explored the possibility of developing asimpler, equally accurate and more user-friendly paradigm forrenal transplant recipients from deceased donors.Methods: Logistic regression analyses addressed the occurrenceof DGF in 532 renal transplant recipients from deceased donors.Predictors consisted of recipient age, gender, race, weight, numberof HLA-A, HLA-B and HLA-DR mismatches, maximum andlast titre of panel reactive antibodies, donor age and cold ischemiatime. Accuracy was quantified with the area under the curve. Twohundred bootstrap resamples were used for internal validation.Results: Delayed graft function occurred in 103 patients (19.4%).Recipient weight (p < 0.001), panel of reactive antibodies (p < 0.001),donor age (p < 0.001), cold ischemia time (p = 0.005) and HLADRmismatches (p = 0.05) represented independent predictors.The multivariable nomogram relying on 6 predictors was 74.3%accurate in predicting the probability of DGF.Conclusion: Our simple and user-friendly model requires 6 variablesand is at least equally accurate (74%) to the previous nomogram(71%). We demonstrate that DGF can be accurately predictedin different populations with this new model.Introduction : La reprise retardée de la fonction (RRF) du greffon,définie comme le besoin de recourir à la dialyse pendant la premièresemaine suivant une transplantation rénale, est une issueclinique indésirable importante. Un modèle proposé antérieurementreposait sur 16 variables pour quantifier le risque de RRF,diminuant ainsi son utilité clinique. Nous avons exploré la possibilitéd’élaborer un paradigme simplifié et plus convivial tout enétant tout aussi précis pour les receveurs de greffons rénauxprovenant de donneurs décédés.Méthodologie : À l’aide d’analyses de régression logistique, nousavons étudié la survenue de la RRF du greffon chez 532 receveursde greffons rénaux provenant de donneurs décédés. Les facteursde prédiction comprenaient l’âge, le sexe, la race et le poids dureceveur et le nombre de non-concordance des phénotypes HLAA,HLA-B et HLA-DR, le titre maximal et le dernier titre d’anticorpsréactifs, l’âge du donneur et la période d’ischémie froide. L’exactitudea été quantifiée par la mesure de la surface sous la courbe. Deuxcents rééchantillonnages par auto-amorçage ont servi à la validationinterne.Résultats : Une reprise retardée de la fonction a été observée chez103 patients (19,4 %). Le poids du receveur (p < 0,001), les anticorpsréactifs (p < 0,001), l’âge du donneur (p < 0,001), la périoded’ischémie froide (p = 0,005) et la non-concordance des phénotypesHLA-DR (p = 0,05) constituaient des facteurs de prédictionindépendants. Le nomogramme multivarié reposant sur 6 facteursde prédiction a permis de prédire avec une exactitude de 74,3 %la probabilité de RRF.Conclusion : Notre modèle simple et convivial nécessite 6 va riableset est au moins tout aussi exact (74 %) que le nomogramme antérieur(71 %). La RRF peut être prévue avec exactitude dans différentespopulations à l’aide ce nouveau modèle, tel que nous en faisonsla démonstration.

2126 DURATION OF DELAYED GRAFT FUNCTION IN RENAL TRANSPLANTATION PREDICTS INTERMEDIATE TERM ALLOGRAFT FUNCTION

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
Michael Moser ◽  
Neal Rowe ◽  
Benjamin Thomson ◽  
Alp Sener ◽  
Patrick Luke
Keyword(s):  
Renal Transplantation ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Allograft Function

Role of Oxidative Stress in Renal Transplantation: Bases for an n-3 PUFA Strategy Against Delayed Graft Function

2017 ◽  
Vol 24 (14) ◽  
Author(s):  
Camilo G. Sotomayor ◽  
Ignacio Cortés ◽  
Juan Guillermo Gormaz ◽  
Sergio Vera ◽  
Matías Libuy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Transplantation ◽  
Graft Function ◽  
Delayed Graft Function

ASSOCIATION OF GRAFT NEUTROPHIL SEQUESTRATION WITH DELAYED GRAFT FUNCTION IN CLINICAL RENAL TRANSPLANTATION

2004 ◽  
Vol 77 (12) ◽  
pp. 1821-1826 ◽  
Author(s):  
Arto J. Turunen ◽  
Leena Lindgren ◽  
Kaija T. Salmela ◽  
Lauri E. Kyll??nen ◽  
Heikki M??kisalo ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Function ◽  
Delayed Graft Function ◽  
Neutrophil Sequestration

P–542 Relationship between the single nucleotides polymorphisms in Mitochondrial Nicotinamide Adenine Dinucleotide Hydride dehydrogenase (NADH) Subunit 4 gene (MT-ND4) and male infertility

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F Dahadhah ◽  
M. Sale Jaweesh ◽  
M. Sali. A Zoubi ◽  
M Issa. Ab. Alarjah ◽  
M Ei Hammadeh ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Male Infertility ◽  
Prospective Study ◽  
Nicotinamide Adenine Dinucleotide ◽  
Mitochondrial Gene ◽  
Genetic Disorders ◽  
Nicotinamide Adenine ◽  
Significant Difference ◽  
Repair Mechanisms ◽  
A Prospective Study

Abstract Study question Is there any association between male infertility and the polymorphic variants of Mitochondrial Nicotinamide Adenine Dinucleotide Hydride dehydrogenase (NADH) Subunit 4 (MT-ND4)? Summary answer Our findings suggested that male infertility was correlated to rs2853495 and rs869096886 SNPs in MTND4. What is known already The rate of mutations in the mtDNA, the powerhouse of the cell, is high due to the lack of histones and DNA repair mechanisms. Therefore, mutations that occur in the mitochondrial genome, play a major role in some human genetic disorders. 15 - 30% of male infertility are related to genetic predisposition. Sperm containing defective mitochondria cannot effectively produce ATP and more likely to produce reactive oxygen species (ROS) and free radicals, thereby causing a defect in mtDNA, make trouble energy, and deteriorate motility and fertility. Study design, size, duration: A prospective study carried out between 2018 and 2019. 112 semen samples were collected in this study. Participants/materials, setting, methods The present study was carried out at the department of Obstetrics and Gynecology, University of Saarland, Germany. Samples were divided into 68 subfertile and 44 fertile men. Mitochondrial DNA was extracted using a QIAamp DNA Mini Kit, after that the mtDNA was amplified by using REPLI-g Mitochondrial DNA Kit. Polymerase chain reaction (PCR) was used to amplify MT-ND4 gene. Then, samples were purified and sequenced using the Sanger method in the Microsynth Seq lab, Germany. Main results and the role of chance The genotypes frequencies of the study population showed a statistically significant association between rs2853495 G&gt;A (Gly320Gly) and male infertility (P = 0.0351). Similarly, the allele frequency test showed that rs2853495 G&gt;A (Gly320Gly) and rs869096886 A&gt;G (Leu164Leu) were significantly associated with male infertility (adjusted OR = 2.616, 95% CI = 1.374 - 4.983, P = 0.0028; adjusted OR = 2.237, 95% CI = 1.245 - 4.017, P = 0.0073, respectively). On the other hand, no statistically significant difference was observed between the asthenozoospermia, oligozoospermia, teratozoospermia, asthenoteratozoospermia, oligoasthenoteratozoospermia, oligoteratozoospermia subgroups of subfertile males and the fertile ones. Limitations, reasons for caution The size number of the study samples. Wider implications of the findings: A larger prospective study will be required to confirm these associations of mitochondrial gene polymorphisms rs2853495 and rs869096886 in MT-ND4 and male infertility and to clarify the definite effect of the mitochondrial genetic variations on male infertility. Trial registration number Not applicable

Intragraft Coagulation Events and Delayed Graft Function in Clinical Renal Transplantation

2008 ◽  
Vol 85 (5) ◽  
pp. 693-699 ◽  
Author(s):  
Arto J. Turunen ◽  
Leena Lindgren ◽  
Kaija T. Salmela ◽  
Lauri E. Kyllönen ◽  
Jari Petäjä ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Graft Function ◽  
Delayed Graft Function
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