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Transplant

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By Venkatesh Ariyamuthu Transplant Nephrologist at UT Southwestern Medical Center
https://www.readbyqxmd.com/read/28993504/precision-transplant-medicine-biomarkers-to-the-rescue
#1
Maarten Naesens, Dany Anglicheau
The concept that individuals with the same disease and a similar clinical presentation may have very different outcomes and need very different therapies is not novel. With the development of many innovative tools derived from the omics technologies, transplant medicine is slowly entering the era of precision medicine. Biomarkers are the cornerstone of precision medicine, which aims to integrate biomarkers with traditional clinical information and tailor medical care to achieve the best outcome for an individual patient...
January 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29847022/identification-of-risk-epitope-mismatches-associated-with-de-novo-donor-specific-hla-antibody-development-in-cardiothoracic-transplantation
#2
J A McCaughan, R K Battle, S K S Singh, J M Tikkanen, Y Moayedi, H J Ross, L G Singer, S Keshavjee, K J Tinckam
The development of de novo donor-specific HLA antibodies (dnDSA) after transplantation is associated with graft failure, mortality, and cost. There is no effective therapeutic intervention to prevent dnDSA or ameliorate associated injury. The aims of this study were to identify specific HLA factors associated with dnDSA development and to propose primary prevention strategies that could reduce the incidence of dnDSA without prohibitively limiting access to transplant. The investigation cohort included heart transplant recipients from 2008 to 2015 (n = 265)...
May 30, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29878640/tolerance-induction-in-kidney-transplantation
#3
EDITORIAL
Lara C Pullen
No abstract text is available yet for this article.
June 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29789350/regulatory-t-cells-and-kidney-transplantation
#4
REVIEW
Paloma Leticia Martin-Moreno, Sudipta Tripathi, Anil Chandraker
The ability of the immune system to differentiate self from nonself is critical in determining the immune response to antigens expressed on transplanted tissue. Even with conventional immunosuppression, acceptance of the allograft is an active process often determined by the presence of regulatory T cells (Tregs). Tregs classically are CD4+ cells that constitutively express high levels of the IL-2 receptor α chain CD25, along with the transcription factor Foxp3. The use of Tregs in the field of solid organ transplantation is related specifically to the objective of achieving tolerance, with the goal of reducing or eliminating immunosuppressive drugs as well as maintaining tissue repair and managing acute rejection...
May 22, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29793969/clinical-pharmacogenomics-applications-in-nephrology
#5
Solomon M Adams, Karryn R Crisamore, Philip E Empey
Pharmacogenomics is a tool for practitioners to provide precision pharmacotherapy using genomics. All providers are likely to encounter genomic data in practice with the expectation that they are able to successfully apply it to patient care. Pharmacogenomics tests for genetic variations in genes that are responsible for drug metabolism, transport, and targets of drug action. Variations can increase the risk for drug toxicity or poor efficacy. Pharmacogenomics can, therefore, be used to help select the best medication or aid in dosing...
May 23, 2018: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29656904/donor-specific-hypo-responsiveness-occurs-in-simultaneous-liver-kidney-transplant-recipients-after-the-first-year
#6
Timucin Taner, Michael P Gustafson, Michael J Hansen, Walter D Park, Svetlana Bornschlegl, Allan B Dietz, Mark D Stegall
Kidney allografts of patients who undergo simultaneous liver-kidney transplantation incur less immune-mediated injury, and retain better function compared to other kidney allografts. To characterize the host alloimmune responses in 28 of these patients, we measured the donor-specific alloresponsiveness and phenotypes of peripheral blood cells after the first year. These values were then compared to those of 61 similarly immunosuppressed recipients of a solitary kidney or 31 recipients of liver allografts. Four multicolor, non-overlapping flow cytometry protocols were used to assess the immunophenotypes...
June 2018: Kidney International
https://www.readbyqxmd.com/read/29787522/belatacept-in-solid-organ-transplant-review-of-current-literature-across-transplant-types
#7
Caroline P Perez, Neha Patel, Caitlin R Mardis, Holly B Meadows, David J Taber, Nicole A Pilch
Calcineurin inhibitors (CNIs) have been the backbone immunosuppressant for solid organ transplant recipients for decades. Long-term use of CNIs unfortunately is associated with multiple toxicities, with the biggest concern being CNI-induced nephrotoxicity. Belatacept is a novel agent approved for maintenance immunosuppression in renal transplant recipients. In the kidney transplant literature, it has shown promise as being an alternative agent by preserving renal function and having a minimal adverse effect profile...
September 2018: Transplantation
https://www.readbyqxmd.com/read/29757909/live-donor-kidney-transplantation-altruism-alone-is-not-always-enough
#8
Michele Molinari, Sundaram Hariharan
No abstract text is available yet for this article.
August 2018: Transplantation
https://www.readbyqxmd.com/read/29762458/association-between-duration-of-delayed-graft-function-acute-rejection-and-allograft-outcome-after-deceased-donor-kidney-transplantation
#9
Wai H Lim, David W Johnson, Armando Teixeira-Pinto, Germaine Wong
BACKGROUND: Prolonged duration of delayed graft function (DGF) may be associated with adverse allograft outcomes, but the association between threshold duration of DGF, acute rejection and long-term allograft loss remains undefined. We aimed to determine the impact of DGF duration on allograft outcomes and to assess whether this association was mediated by acute rejection. METHODS: Using data from the Australian and New Zealand Dialysis and Transplant (ANZDATA) registry, Cox proportional modelling was used to determine the association between quartiles of DGF duration, acute rejection at 6 months and death-censored graft loss (DCGL)...
May 14, 2018: Transplantation
https://www.readbyqxmd.com/read/29733390/increase-in-tacrolimus-exposure-after-steroid-tapering-is-influenced-by-cyp3a5-and-pregnane-x-receptor-genetic-polymorphisms-in-renal-transplant-recipients
#10
Frank Stifft, Sander M J van Kuijk, Otto Bekers, Maarten H L Christiaans
Background: Tacrolimus, a drug for prevention of rejection after kidney transplantation, has a narrow therapeutic window and is metabolized by the cytochrome P540 3A (CYP3A) system. Tacrolimus exposure increases after steroid tapering in many patients. The pregnane X receptor (PXR)-a mediator for CYP3A-has a steroid receptor and might regulate CYP3A5 activity depending on single nucleotide polymorphisms (SNPs) of CYP3A5 or PXR. This may contribute to differences in tacrolimus exposure after steroid tapering...
May 3, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29716794/proliferative-glomerulonephritis-with-monoclonal-immunoglobulin-g-deposits-is-associated-with-high-rate-of-early-recurrence-in-the-allograft
#11
Samar M Said, Fernando G Cosio, Anthony M Valeri, Nelson Leung, Sanjeev Sethi, Hassan Salameh, Lynn D Cornell, Mary E Fidler, Mariam P Alexander, Fernando C Fervenza, Maria Eleni Drosou, Da Zhang, Vivette D D'Agati, Samih H Nasr
The characteristics of allograft proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) are not well defined. To better characterize this disease we retrospectively identified 26 patients with allograft PGNMID, including 16 followed with early protocol biopsies. PGNMID was found to be a recurrent disease in most (89%) patients. A diagnostic biopsy was done for proteinuria and/or increased creatinine in most patients. Median time from transplant to diagnostic biopsy was 5.5 months, with detection within three to four months post-transplant in 86% of patients...
July 2018: Kidney International
https://www.readbyqxmd.com/read/29464832/differential-effects-of-donor-specific-hla-antibodies-in-living-versus-deceased-donor-transplant
#12
E G Kamburova, B W Wisse, I Joosten, W A Allebes, A van der Meer, L B Hilbrands, M C Baas, E Spierings, C E Hack, F E van Reekum, A D van Zuilen, M C Verhaar, M L Bots, A C A D Drop, L Plaisier, M A J Seelen, J S F Sanders, B G Hepkema, A J A Lambeck, L B Bungener, C Roozendaal, M G J Tilanus, C E Voorter, L Wieten, E M van Duijnhoven, M Gelens, M H L Christiaans, F J van Ittersum, S A Nurmohamed, N M Lardy, W Swelsen, K A van der Pant, N C van der Weerd, I J M Ten Berge, F J Bemelman, A Hoitsma, P J M van der Boog, J W de Fijter, M G H Betjes, S Heidt, D L Roelen, F H Claas, H G Otten
The presence of donor-specific anti-HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long-term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement-dependent crossmatch...
September 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29509285/impact-of-the-new-kidney-allocation-system-a2-a2b-%C3%A2-b-policy-on-access-to-transplantation-among-minority-candidates
#13
Paulo N Martins, Margaux N Mustian, Paul A MacLennan, Jorge A Ortiz, Mohamed Akoad, Juan Carlos Caicedo, Gabriel J Echeverri, Stephen H Gray, Reynold I Lopez-Soler, Ganesh Gunasekaran, Beau Kelly, Constance M Mobley, Sylvester M Black, Carlos Esquivel, Jayme E Locke
Blood group B candidates, many of whom represent ethnic minorities, have historically had diminished access to deceased donor kidney transplantation (DDKT). The new national kidney allocation system (KAS) preferentially allocates blood group A2/A2B deceased donor kidneys to B recipients to address this ethnic and blood group disparity. No study has yet examined the impact of KAS on A2 incompatible (A2i) DDKT for blood group B recipients overall or among minorities. A case-control study of adult blood group B DDKT recipients from 2013 to 2017 was performed, as reported to the Scientific Registry of Transplant Recipients...
August 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29524307/plasma-cell-diseases-and-organ-transplant-a-comprehensive-review
#14
REVIEW
Andrew J Cowan, Christopher K Johnson, Edward N Libby
Plasma cell diseases are a class of hematologic diseases that are sometimes present as preexisting diagnoses prior to organ transplantation, causative factors leading to a need for organ transplantation, or may occur posttransplant as part of the spectrum of posttransplant lymphoproliferative disorders. Herein, we review the most common plasma cell diseases, both as coexisting with other causes of organ failure, but also as a primary underlying cause for organ failure. In many cases, treatment of the underlying clonal disease may be indicated before proceeding with organ transplant...
May 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29573335/posttransplant-reduction-in-preexisting-donor-specific-antibody-levels-after-belatacept-versus-cyclosporine-based-immunosuppression-post-hoc-analyses-of-benefit-and-benefit-ext
#15
R A Bray, H M Gebel, R Townsend, M E Roberts, M Polinsky, L Yang, H-U Meier-Kriesche, C P Larsen
BENEFIT and BENEFIT-EXT were phase III studies of cytotoxic T-cell crossmatch-negative kidney transplant recipients randomized to belatacept more intense (MI)-based, belatacept less intense (LI)-based, or cyclosporine-based immunosuppression. Following study completion, presence/absence of HLA-specific antibodies was determined centrally via solid-phase flow cytometry screening. Stored sera from anti-HLA-positive patients were further tested with a single-antigen bead assay to determine antibody specificities, presence/absence of donor-specific antibodies (DSAs), and mean fluorescent intensity (MFI) of any DSAs present...
July 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29575655/potential-implications-of-a-more-timely-living-kidney-donor-evaluation
#16
Steven Habbous, Eric McArthur, Sisira Sarma, Mehmet A Begen, Ngan N Lam, Braden Manns, Krista L Lentine, Christine Dipchand, Kenneth Litchfield, Susan McKenzie, Amit X Garg
Living donor kidney transplantation is the most promising way to avoid or minimize the amount of time a recipient spends on dialysis before transplantation. We studied 887 living kidney donors at 5 transplant centers in Ontario, Canada, who started their evaluation and donated between April 2006 and March 2014. Using a series of hypothetical scenarios, we estimated the impact of an earlier living donor evaluation completion and donation on the number pre-emptive transplants, the time spent on dialysis, healthcare cost savings from averted dialysis costs (CAD $2016), and the number of additional transplants...
March 25, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29603613/sensitization-in-transplantation-assessment-of-risk-star-2017-working-group-meeting-report
#17
Anat R Tambur, Patricia Campbell, Frans H Claas, Sandy Feng, Howard M Gebel, Annette M Jackson, Roslyn B Mannon, Elaine F Reed, Kathryn Tinckam, Medhat Askar, Anil Chandraker, Patricia P Chang, Monica Colvin, Anthony-Jake Demetris, Joshua M Diamond, Anne I Dipchand, Robert L Fairchild, Mandy L Ford, John Friedewald, Ronald G Gill, Denis Glotz, Hilary Goldberg, Ramsey Hachem, Stuart Knechtle, Jon Kobashigawa, Deborah J Levine, Joshua Levitsky, Michael Mengel, Edgar Milford, Kenneth A Newell, Jacqueline G O'Leary, Scott Palmer, Parmjeet Randhawa, John Smith, Laurie Snyder, Randall C Starling, Stuart Sweet, Timucin Taner, Craig J Taylor, Steve Woodle, Adriana Zeevi, Peter Nickerson
The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation...
July 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29603637/carpe-diem-time-to-transition-from-empiric-to-precision-medicine-in-kidney-transplantation
#18
Chris Wiebe, Julie Ho, Ian W Gibson, David N Rush, Peter W Nickerson
The current immunosuppressive pipeline in kidney transplantation is limited. In part, this is due to excellent one-year allograft outcomes with the current standard of care (ie, calcineurin inhibitor in combination with anti-proliferative agents). Despite this success, a recent Federal government-sponsored systematic review has identified gaps/limits in the evidence of what constitutes optimal calcineurin inhibitor use in the short- and long-term. Moreover, recent empiric approaches to minimize/withdraw/convert from calcineurin inhibitors have come with the price of increased alloreactivity...
July 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29603640/the-first-9-years-of-kidney-paired-donation-through-the-national-kidney-registry-characteristics-of-donors-and-recipients-compared-with-national-live-donor-transplant-registries
#19
Stuart M Flechner, Alvin G Thomas, Matthew Ronin, Jeffrey L Veale, David B Leeser, Sandip Kapur, John D Peipert, Dorry L Segev, Macey L Henderson, Ashton A Shaffer, Matthew Cooper, Garet Hil, Amy D Waterman
The practice of kidney paired donation (KPD) is expanding annually, offering the opportunity for live donor kidney transplant to more patients. We sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or recipients compared with national registries. For this purpose, we merged data from the NKR database with the Scientific Registry of Transplant Recipients (SRTR) database, from February 14, 2008, to February 14, 2017, encompassing the first 9 years of the NKR...
March 30, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29607610/recurrent-igg4-related-tubulointerstitial-nephritis-concurrent-with-chronic-active-antibody-mediated-rejection-a-case-report
#20
Rajni Chibbar, Glenda R Wright, Pouneh Dokouhaki, Sandi Dumanski, Bhanu Prasad, Michael Mengel, Lynn D Cornell, Ahmed Shoker
IgG4-related disease is a relatively newly described entity that can affect nearly any organ, including the kidneys, where it usually manifests as tubulointerstitial nephritis (IgG4-TIN). The diagnosis can be suggested by characteristic histological features, including an inflammatory infiltrate with increased IgG4-positive plasma cells associated with "storiform" fibrosis. Serum IgG4 is usually elevated. In the native kidney and other organs, there is typically a brisk response to treatment with immunosuppression...
July 2018: American Journal of Transplantation
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