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fewer and kidney allograft

G Varela-Fascinetto, C Benchimol, R Reyes-Acevedo, M Genevray, D Bradley, J Ives, H T Silva
This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21...
October 17, 2016: Pediatric Transplantation
Randula Ranawaka, Carla Lloyd, Pat J McKiernan, Sally A Hulton, Khalid Sharif, David V Milford
BACKGROUND: Combined liver-kidney transplantation (CLKT) is the accepted treatment for patients with both liver failure and progressive renal insufficiency. Long-term outcome data for CLKT in children is sparse and controversy exists as to whether simultaneous CLKT with organs from the same donor confers immunologic and survival benefit to the kidney allograft. We report the long-term renal graft outcomes of 40 patients who had simultaneous CLKT. METHODS: A retrospective analysis of kidney graft survival (time from transplantation to death, return to dialysis or last follow-up event) in all pediatric patients (age < 18 years old) who underwent CLKT from March 1994 to January 2015...
September 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Vijay Subramanian, Muthukumar Gunasekaran, Joseph P Gaut, Donna Phelan, Neeta Vachharajani, Rowena Delos Santos, Jason Wellen, Surendra Shenoy, T Mohanakumar
Immune responses to HLA and tissue-restricted self-antigens (SAgs) have been proposed to play a role in the pathogenesis of renal allograft (KTx) rejection. However, ABO incompatible (ABOi) KTx recipients (KTxR) following depletion of antibodies (Abs) to blood group antigens had fewer rejections. To determine the mechanisms, pre- and post-transplant sera from ABOi (n=18) and ABO-compatible (ABOc) (n=45) KTxR were analyzed for Abs against HLA class I and II by LABScreen single antigen assay. The development of Abs to SAgs was measured by ELISA...
January 2016: Human Immunology
R Brian Stevens, Kirk W Foster, Clifford D Miles, Andre C Kalil, Diana F Florescu, John P Sandoz, Theodore H Rigley, Tamer Malik, Lucile E Wrenshall
INTRODUCTION: The two most significant impediments to renal allograft survival are rejection and the direct nephrotoxicity of the immunosuppressant drugs required to prevent it. Calcineurin inhibitors (CNI), a mainstay of most immunosuppression regimens, are particularly nephrotoxic. Until less toxic antirejection agents become available, the only option is to optimize our use of those at hand. AIM: To determine whether intensive rabbit anti-thymocyte globulin (rATG) induction followed by CNI withdrawal would individually or combined improve graft function and reduce graft chronic histopathology-surrogates for graft and, therefore, patient survival...
2015: PloS One
Pamela M Kimball, Felecia A McDougan, Anne King
We used a simple point-based algorithm to identify patients who might benefit from desensitization because of their higher risk of antibody-mediated chronic rejection and graft failure. Points were assigned to known but easily determined risk factors (panel reactive antibody, flow crossmatch, delayed graft function) and calculated immediately after deceased donor kidney transplantation. Point totals were used to identify: 1) which patients would receive desensitization; and, 2) which regimen each patient would receive...
2014: Clinical Transplants
F G Cosio, M El Ters, L D Cornell, C A Schinstock, M D Stegall
Allograft histology 1 year posttransplant is an independent correlate to long-term death-censored graft survival. We assessed prognostic implications of changes in histology first 2 years posttransplant in 938 first kidney recipients, transplanted 1999-2010, followed for 93.4 ± 37.7 months. Compared to implantation biopsies, histology changed posttransplant showing at 1 year that 72.6% of grafts had minor abnormalities (favorable histology), 20.2% unfavorable histology, and 7.2% glomerulonephritis. Compared to favorable, graft survival was reduced in recipients with unfavorable histology (hazards ratio [HR] = 4...
January 2016: American Journal of Transplantation
Erwan Dumontet, Richard Danger, Parsia A Vagefi, Maria-Carlota Londoño, Annaïck Pallier, Juan José Lozano, Magali Giral, Nicolas Degauque, Jean-Paul Soulillou, Marc Martínez-Llordella, Herman Lee, Marianne Latournerie, Karim Boudjema, Joelle Dulong, Karin Tarte, Alberto Sanchez-Fueyo, Sandy Feng, Sophie Brouard, Sophie Conchon
BACKGROUND AND AIMS: The beneficial effect of one graft on another has been reported in combined transplantation but the associated mechanisms and biological influence of each graft have not yet been established. METHODS: In multiple analyses, we explored the PBMC phenotype and signature of 45 immune-related messenger RNAs and 754 microRNAs from a total of 235 patients, including combined liver-kidney transplant recipients (CLK), patients with a liver (L-STA) or kidney (K-STA) graft only under classical immunosuppression and patients with tolerated liver (L-TOL) or kidney grafts (K-TOL)...
March 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Željko Kikić, Alexander Kainz, Nicolas Kozakowski, Rainer Oberbauer, Heinz Regele, Gregor Bond, Georg A Böhmig
BACKGROUND AND OBJECTIVES: Recent studies highlighting a role of C4d- antibody-mediated rejection (ABMR) have debated whether C4d staining has independent value as a rejection marker. Considering the presumed role of complement as an important effector of graft injury, this study hypothesized that capillary C4d, a footprint of antibody-triggered complement activation, indicates a particularly severe manifestation of ABMR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This large retrospective clinicopathologic study sought to assess the clinical predictive value of C4d staining in relation to ABMR morphology...
August 7, 2015: Clinical Journal of the American Society of Nephrology: CJASN
Samer M T Al-Geizawi, Rajinder P Singh, Jack M Zuckerman, Jay A Requarth, Alan C Farney, Jeffrey Rogers, Jacob Taussig, Giuseppe Orlando, Robert J Stratta
INTRODUCTION: Allograft nephrectomy (AN) is not without morbidity following graft failure (GF) in kidney transplantation (KT). METHODS: Single center retrospective review of all adult patients undergoing AN following KT, including a subset of patients who underwent pre-operative angiographic kidney embolization (PAKE). RESULTS: Over a 104 month period, 853 adult patients underwent deceased donor KT. With a median follow-up of 3.5 years, 174 patients (20...
June 2015: Journal of Nephrology
T Kawai, D H Sachs, B Sprangers, T R Spitzer, S L Saidman, E Zorn, N Tolkoff-Rubin, F Preffer, K Crisalli, B Gao, W Wong, H Morris, S A LoCascio, P Sayre, B Shonts, W W Williams, R-N Smith, R B Colvin, M Sykes, A B Cosimi
We report here the long-term results of HLA-mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All subjects were treated with nonmyeloablative conditioning and an 8- to 14-month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4...
July 2014: American Journal of Transplantation
Miae Kim, Spencer T Martin, Keri R Townsend, Steven Gabardi
Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently...
July 2014: Pharmacotherapy
Maureen Ezeakile, Vera Portik-Dobos, Juan Wu, Daniel D Horuzsko, Rajan Kapoor, Muralidharan Jagadeesan, Laura L Mulloy, Anatolij Horuzsko
Human leukocyte antigen-G (HLA-G) contributes to acceptance of allografts in solid organ/tissue transplantation. Most studies have determined that soluble HLA-G isoforms are systematically detected in serum/plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue/organ. Current models of the interactions of HLA-G and its specific receptors explain it as functioning in a monomeric form. However, in recent years, new data has revealed the ability of HLA-G to form disulfide-linked dimeric complexes with high preferential binding and functional activities...
2014: Journal of Immunology Research
Jürgen Kaden, Dietmar Abendroth, Andreas Völp, Michael Marzinzig, Claus Wesslau
BACKGROUND: The activation of the tryptophane catabolizing enzyme Indoleamine 2,3-dioxygenase leads to the formation of kynurenine and other metabolites that counter-regulate immune activation resulting in restoration of immune homeostasis. But in chronic immune activation, as in hemodialysed patients, the immunosuppressive feedback mechanisms continue as indicated by elevated kynurenine concentrations. However, its relevance is still a matter of debate. MATERIAL/METHODS: This retrospective analysis presents the pre-transplant kynurenine levels (quantified photometrically) of 307 kidney graft recipients in connection with some pre- and post-transplant variables and the type of immunosuppression (cyclosporine-based triple drug therapy without/with ATG-Fresenius-induction)...
2014: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Susan C Pitt, Neeta Vachharajani, Maria B Doyle, Jeffrey A Lowell, William C Chapman, Christopher D Anderson, Surendra Shenoy, Jason R Wellen
The 2005 revised allocation scheme for pediatric renal transplantation made the decision of whether to transplant an available living-donor (LD) kidney or use a deceased-donor (DD) kidney controversial. The aim of this study was to examine kidney allograft utilization, sensitization, and outcomes of pediatric transplant recipients. Between January 2000 and December 2009, 91 consecutive pediatric kidney recipients (<20 yr) were transplanted. The LD (n = 38) and DD (n = 53) groups were similar in age, gender, dialysis status at transplant, warm ischemia time, and overall patient survival...
November 2013: Clinical Transplantation
John H Pang, Farah Karipineni, Heena Panchal, Stalin Campos, Jorge Ortiz
INTRODUCTION: The "July effect" is a widely discussed phenomenon of worse patient outcomes at teaching hospitals in July due to inexperienced house staff. METHODS: We conducted a retrospective review of Organ Procurement and Transplantation Network data from Oct 1, 1987 to June 30, 2011, including longitudinal censored data of 360,330 transplantations. Demographic and comorbid variables for donors and recipients were collected. Primary outcomes were graft loss, patient death, and delayed graft function...
May 2013: Journal of Surgical Education
Qiunong Guan, Shuyuan Li, Sihai Gao, Huifang Chen, Christopher Y C Nguan, Caigan Du
There is no effective treatment for chronic rejection (CR) that largely limits long-term survival of kidney transplants. Transforming growth factor (TGF)-β is a fibrogenic factor for tissue fibrosis. This study was to test the efficacy of an anti-TGF-β antibody in preventing the CR of renal allografts in a preclinical model. Male Lewis rats (RT1¹) were orthotopically transplanted with donor kidneys from male Fischer 344 (RT11v1) rats and were treated with either anti-TGF-β or a control antibody. The CR of renal allografts was assessed by semiquantitative histological analyses, and intragraft cytokines and fibrosis-related genes ware examined by PCR arrays...
July 15, 2013: American Journal of Physiology. Renal Physiology
Karlijn J Van Stralen, Enrico Verrina, Mirco Belingheri, Jan Dudley, Jirí Dusek, Ryszard Grenda, Marie-Alice Macher, Zvonimir Puretic, Jacek Rubic, Sarunas Rudaitis, Christoph Rudin, Franz Schaefer, Kitty J Jager
BACKGROUND: Some kidney diseases tend to recur in the renal allograft after transplantation. We studied the risk of graft loss among primary renal diseases known for their high risk of recurrence and compared it with that of patients with hypoplasia and/or dysplasia. METHODS: Within the European Society of Paediatric Nephrology and European Renal Association and European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry, we studied children from 33 countries who received a kidney transplant before the age of 20 between 1990 and 2009...
April 2013: Nephrology, Dialysis, Transplantation
Heidi Braun, Bernhard M W Schmidt, Mirja Raiss, Arpita Baisantry, Dan Mircea-Constantin, Shijun Wang, Marie-Luise Gross, Manuel Serrano, Roland Schmitt, Anette Melk
Long-term graft survival after kidney transplantation remains unsatisfactory and unpredictable. Interstitial fibrosis and tubular atrophy are major contributors to late graft loss; features of tubular cell senescence, such as increased p16(INK4a) expression, associate with these tubulointerstitial changes, but it is unknown whether the relationship is causal. Here, loss of the INK4a locus in mice, which allows escape from p16(INK4a)-dependent senescence, significantly reduced interstitial fibrosis and tubular atrophy and associated with improved renal function, conservation of nephron mass, and transplant survival...
September 2012: Journal of the American Society of Nephrology: JASN
F Vincenti, H Tedesco Silva, S Busque, P O'Connell, J Friedewald, D Cibrik, K Budde, A Yoshida, S Cohney, W Weimar, Y S Kim, N Lawendy, S-P Lan, E Kudlacz, S Krishnaswami, G Chan
In this Phase 2b study, 331 low-to-moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of tofacitinib (CP-690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy-proven acute rejection (BPAR) with a serum creatinine increase of ≥0.3 mg/dL and ≥20% (clinical BPAR) at Month 6 and measured GFR at Month 12...
September 2012: American Journal of Transplantation
John C LaMattina, Joshua D Mezrich, R Michael Hofmann, David P Foley, Anthony M D'Alessandro, Hans W Sollinger, John D Pirsch
Between 1 January 2002 and 31 December 2007, our center performed 1687 adult renal transplants. A retrospective analysis was performed to compare outcomes between patients receiving alemtuzumab (n = 632) and those receiving either basiliximab (n = 690) or thymoglobulin (n = 125). Patients receiving alemtuzumab were younger (49 vs. 51 years, P = 0.02), had fewer HLA matches (1.7 vs. 2.0, P < 0.0001), were more likely to have a cytomegalovirus (CMV) donor(+)/recipient(-) transplant (22% vs. 17%, P = 0.03) and were less likely to receive a living donor allograft (32% vs...
May 2012: Transplant International: Official Journal of the European Society for Organ Transplantation
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