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algorithm, kidney transplant rejection

Daniel Zecher, Christian Bach, Adrian Preiss, Christoph Staudner, Kirsten Utpatel, Matthias Evert, Bettina Jung, Tobias Bergler, Carsten A Böger, Bernd M Spriewald, Bernhard Banas
BACKGROUND: HLA-specific antibodies detected by solid phase assays are increasingly used to define unacceptable HLA antigen mismatches (UAM) prior to renal transplantation. The accuracy of this approach is unclear. METHODS: Day of transplant sera from 211 CDC-crossmatch-negative patients were retrospectively analyzed for donor-specific anti-HLA antibodies (DSA) using Luminex technology. HLA were defined as UAM if DSA had mean fluorescence intensity above (I) 3000 (patients retransplanted and those with DSA against HLA class I and II) or 5000 (all other patients), (II) 5000 for HLA A, B and DR and 10,000 for HLA DQ or (III) 10,000 (all HLA)...
February 20, 2018: Transplantation
Miklos Z Molnar, James D Eason, Abduzhappar Gaipov, Manish Talwar, Praveen K Potukuchi, Kiran Joglekar, Adam Remport, Zoltan Mathe, Istvan Mucsi, Marta Novak, Kamyar Kalantar-Zadeh, Csaba P Kovesdy
History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models...
February 6, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Ryszard Grenda, Piotr Kaliciński
Combined and sequential liver-kidney transplantation (CLKT and SLKT) is a definitive treatment in children with end-stage organ failure. There are two major indications: - terminal insufficiency of both organs, or - need for transplanting new liver as a source of lacking enzyme or specific regulator of the immune system in a patient with renal failure. A third (uncommon) option is secondary end-stage renal failure in liver transplant recipients. These three clinical settings use distinct qualification algorithms...
January 10, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Francisco Salcido-Ochoa, John Carson Allen
A literature review on immune monitoring in kidney transplantation produced dozens of research articles and a multitude of promising biomarkers, all in the quest for the much sought after - but perennially elusive - "holy grail" of kidney biomarkers able to unequivocally predict acute transplant rejection vs non-rejection. Detection methodologies and study designs were many and varied. Hence the motivation for this editorial, which espouses the notion that in today's kidney transplantation milieu, the judicious use of disease classifiers tailored to specific patient immune risks may be more achievable and productive in the long run and confer a greater advantage for patient treatment than the pursuit of a single "omniscient" biomarker...
December 24, 2017: World Journal of Transplantation
Tianyu Kang, Wei Ding, Luoyan Zhang, Daniel Ziemek, Kourosh Zarringhalam
BACKGROUND: Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers...
December 19, 2017: BMC Bioinformatics
Philip F Halloran, Jeffery M Venner, Katelynn S Madill-Thomsen, Gunilla Einecke, Michael D Parkes, Luis G Hidalgo, Konrad S Famulski
The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants...
November 25, 2017: American Journal of Transplantation
Peng Jin, Hongxi Chen, Jinliang Xie, Cheng Zhou, Xiangrong Zhu
Kidney transplantation is an effective final therapeutic procedure for patients with end-stage kidney failure. Although advanced immunosuppressive therapy is administered following transplantation, certain patients still suffer from acute allograft rejection. MicroRNAs (miRs) have a potential diagnostic and therapeutic value for acute renal allograft rejection; however, their underlying mechanism of action is largely unknown. In the present study, an increased level of miR-650 was identified to be associated with the downregulation of B-cell CLL/lymphoma 11B (BCL11B) expression in acute renal allograft rejection...
October 17, 2017: International Journal of Molecular Medicine
Agnieszka Bierzynska, Moin A Saleem
After renal transplantation, recurrence of the original disease is the second most common cause of graft loss, after rejection. The most dramatic manifestation of this phenomenon is in patients with nephrotic syndrome (NS). NS is a descriptive term describing a clinical picture centred on proteinuria arising from damage to the glomerular filtration barrier (GFB). There are many different drivers of that damage, ranging from immune dysregulation to genetic disorders and chronic disease/infections. The main categories in childhood are "idiopathic" (presumed immune mediated) and genetic NS, with further stratification of the idiopathic group according to steroid responses...
October 11, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Kyung Don Yoo, Junhyug Noh, Hajeong Lee, Dong Ki Kim, Chun Soo Lim, Young Hoon Kim, Jung Pyo Lee, Gunhee Kim, Yon Su Kim
Accurate prediction of graft survival after kidney transplant is limited by the complexity and heterogeneity of risk factors influencing allograft survival. In this study, we applied machine learning methods, in combination with survival statistics, to build new prediction models of graft survival that included immunological factors, as well as known recipient and donor variables. Graft survival was estimated from a retrospective analysis of the data from a multicenter cohort of 3,117 kidney transplant recipients...
August 21, 2017: Scientific Reports
Eilon Sharon, Hao Shi, Sandhya Kharbanda, Winston Koh, Lance R Martin, Kiran K Khush, Hannah Valantine, Jonathan K Pritchard, Iwijn De Vlaminck
Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable...
August 2017: PLoS Computational Biology
Tara K Sigdel, Minnie M Sarwal
Identification and use of non-invasive biomarkers for kidney transplantation monitoring is an unmet need. A total of 121 biobanked sera collected from 111 unique kidney transplant (KT) patients (children and adolescent) and 10 age-matched healthy normal controls were used to profile serum proteins using semi-quantitative proteomics. The proteomics data were analyzed to identify panels of serum proteins that were specific to various transplant injuries, which included acute rejection (AR), BK virus nephropathy (BKVN), and chronic allograft nephropathy (CAN)...
2017: Frontiers in Medicine
P F Halloran, J Reeve, E Akalin, O Aubert, G A Bohmig, D Brennan, J Bromberg, G Einecke, F Eskandary, C Gosset, J-P Duong Van Huyen, G Gupta, C Lefaucheur, A Malone, R B Mannon, D Seron, J Sellares, M Weir, A Loupy
The authors conducted a prospective trial to assess the feasibility of real time central molecular assessment of kidney transplant biopsy samples from 10 North American or European centers. Biopsy samples taken 1 day to 34 years posttransplantation were stabilized in RNAlater, sent via courier overnight at ambient temperature to the central laboratory, and processed (29 h workflow) using microarrays to assess T cell- and antibody-mediated rejection (TCMR and ABMR, respectively). Of 538 biopsy samples submitted, 519 (96%) were sufficient for microarray analysis (average length, 3 mm)...
November 2017: American Journal of Transplantation
S M Kurian, E Velazquez, R Thompson, T Whisenant, S Rose, N Riley, F Harrison, T Gelbart, J J Friedewald, J Charette, S Brietigam, J Peysakhovich, M R First, M M Abecassis, D R Salomon
We performed orthogonal technology comparisons of concurrent peripheral blood and biopsy tissue samples from 69 kidney transplant recipients who underwent comprehensive algorithm-driven clinical phenotyping. The sample cohort included patients with normal protocol biopsies and stable transplant (sTx) function (n = 25), subclinical acute rejection (subAR, n = 23), and clinical acute rejection (cAR, n = 21). Comparisons between microarray and RNA sequencing (RNA-seq) signatures were performed and demonstrated a strong correlation between the blood and tissue compartments for both technology platforms...
August 2017: American Journal of Transplantation
Leila Shahmoradi, Mostafa Langarizadeh, Gholamreza Pourmand, Ziba Aghsaei Fard, Alireza Borhani
INTRODUCTION: One of the most important complications of post-transplant is rejection. Analyzing survival is one of the areas of medical prognosis and data mining, as an effective approach, has the capacity of analyzing and estimating outcomes in advance through discovering appropriate models among data. The present study aims at comparing the effectiveness of C5.0 algorithms, neural network and C&RTree to predict kidney transplant survival before transplant. METHOD: To detect factors effective in predicting transplant survival, information needs analysis was performed via a researcher-made questionnaire...
October 2016: Acta Informatica Medica: AIM
D Iwami, K Hotta, H Sasaki, T Hirose, H Higuchi, Y Takada, N Shinohara
BACKGROUND: De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited...
January 2017: Transplantation Proceedings
P F Halloran, J M Venner, K S Famulski
We annotated the top transcripts associated with kidney transplant rejection by p-value, either universal for all rejection or selective for T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR; NCT01299168). We used eight class-comparison algorithms to interrogate microarray results from 703 biopsies, 205 with rejection. The positive comparators were all rejection, TCMR, or ABMR; the negative comparators varied from normal biopsies to all nonrejecting biopsies, including other diseases...
July 2017: American Journal of Transplantation
Dong Zhu, Zexian Liu, Zhicheng Pan, Mengjia Qian, Linyan Wang, Tongyu Zhu, Yu Xue, Duojiao Wu
For end-stage renal diseases, kidney transplantation is the most efficient treatment. However, the unexpected rejection caused by inflammation usually leads to allograft failure. Thus, a systems-level characterization of inflammation factors can provide potentially diagnostic biomarkers for predicting renal allograft rejection. Serum of kidney transplant patients with different immune status were collected and classified as transplant patients with stable renal function (ST), impaired renal function with negative biopsy pathology (UNST), acute rejection (AR), and chronic rejection (CR)...
August 2016: Cell Biology and Toxicology
Amber O Molnar, Carl van Walraven, Eric McArthur, Dean Fergusson, Amit X Garg, Greg Knoll
BACKGROUND: Validation studies of acute kidney injury (AKI) diagnostic codes performed in the general population have shown poor sensitivity, but the accuracy of such codes in the kidney transplant population remains unknown. OBJECTIVE: The objective of this study is to determine the accuracy of AKI diagnostic codes in kidney transplant recipients. We hypothesized that the sensitivity of diagnostic codes would be significantly greater in the kidney transplant population since these patients are closely followed by nephrologists and are more likely to have serum creatinine measured...
2016: Canadian Journal of Kidney Health and Disease
Wai H Lim, Jeremy R Chapman, Patrick T Coates, Joshua R Lewis, Graeme R Russ, Narelle Watson, Rhonda Holdsworth, Germaine Wong
BACKGROUND AND OBJECTIVES: The current allocation algorithm for deceased donor kidney transplantation takes into consideration HLA mismatches at the ABDR loci but not HLA mismatches at other loci, including HLA-DQ. However, the independent effects of incompatibilities for the closely linked HLA-DQ antigens in the context of HLA-DR antigen matched and mismatched allografts are uncertain. We aimed to determine the effect of HLA-DQ mismatches on renal allograft outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the association between HLA-DQ mismatches and acute rejections in primary live and deceased donor kidney transplant recipients between 2004 and 2012 using adjusted Cox regression models...
May 6, 2016: Clinical Journal of the American Society of Nephrology: CJASN
Felix S Seibert, Christian Rosenberger, Susanne Mathia, Robert Arndt, Wolfgang Arns, Huppertz Andrea, Nikolaos Pagonas, Frederic Bauer, Walter Zidek, Timm H Westhoff
BACKGROUND: Urinary calprotectin has recently been identified as a promising biomarker for the differentiation between prerenal and intrinsic acute kidney injury (AKI) in the nontransplant population. The present study investigates whether calprotectin is able to differentiate between these 2 entities in transplant recipients as well. METHODS: Urinary calprotectin was assessed by enzyme-linked immunosorbent assay in 328 subjects including 125 cases of intrinsic acute allograft failure, 27 prerenal graft failures, 118 patients with stable graft function, and 58 healthy controls...
February 2017: Transplantation
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