Virtual Issues

Virtual issues are collections of articles on a particular subject, published in the American Journal of Transplantation. They are selected by a guest editor to provide a rapid overview of the activity in a particular aspect of transplantation. The virtual issues will be updated on a regular basis by the editor, but will not be available as a paper publication.

The following virtual issues are available:

 


Viral Infections

Guest Editor: Emily Blumberg, MD

Viral infections are a major source of morbidity and mortality following solid organ transplantation. These infections may be present in the recipient prior to transplant, acquired from the donor, or acquired via exposure in the posttransplant setting. Recent articles provide new insights into some of the major viral infections seen in transplant recipients, including Cytomegalovirus, Epstein Barr Virus, Human herpesvirus 8, Polyomavirus, Human T cell lymphotrophic virus 1/2, and Influenza, expanding our understanding of risk factors and outcomes related to these viruses.

Additionally, high-profile transmissions of Human Immunodeficiency Virus and Hepatitis C have drawn attention to identification of donor risk factors associated with these infections with the goal of expanding our understanding of which donors would be most likely to transmit these blood-borne viruses to recipients.

The articles in this virtual issue highlight recent developments in viral infections, focusing on preventive measures including vaccination, immune-modulation, and identification of at-risk donors, as well as factors associated with more severe complications of infection. This issue features clinically relevant articles with the goal of expanding our understanding of why viral infections have such a significant impact on transplant outcomes.

References:

BK Virus

Hardinger KL, et al. BK-Virus and the impact of pre-emptive immunosuppression reduction: 5-year results. 10:407-15.

Dharnidharka VR, et al. Retransplantation after BK virus nephropathy in prior kidney transplant: an OPTN database analysis. 10:1312-15.

Cytomegalovirus

Paraskeva M, et al. Cytomegalovirus replication within the lung allograft is associated with bronchiolitis obliterans. 11:2190-6.

Brennan DC, et al. Cytomegalovirus incidence between everolimus versus mycophenolate in de novo renal transplants: pooled analysis of three clinical trials. 11:2453-62.

Bosch W, et al. Association of cytomegalovirus infection and disease with death and graft loss after liver transplant in high-risk recipients. 11:2181-89.

Eid AJ, et al. Clinical predictors of relapse after treatment of primary gastrointestinal cytomegalovirus disease in solid organ transplant recipients. 10:157-61.

Patel N, et al. Is prevention the best treatment? CMV after lung transplantation. 12:639-44.

Snyder LD, et al. Polyfunctional Cytomegalovirus-specific immunity in lung transplant recipients receiving valganciclovir prophylaxis. 11:553-60.

Couzi L, et al. High incidence of anticytomegalovirus drug resistance among D+R- kidney transplant recipients receiving preemptive therapy. 12:202-9.

Gerna G, et al. Virologic and immunologic monitoring of Cytomegalovirus to guide preemptive therapy in solid organ transplantation. 11:2463-71.

Gala-Lopez BL, et al. Late Cytomegalovirus transmission and impact of T-depletion in clinical islet transplantation. 11:2708-14.

Luan FL, et al. Impact of Cytomegalovirus disease in D+R- kidney transplant patients receiving 6 months low-dose valganciclovir prophylaxis. 11:1936-42.

Helantera I, et al. Primary CMV infections are common in kidney transplant recipients after 6 months valganciclovir prophylaxis. 10:2026-32.

Humar A, et al. The efficacy and safety of 200 days valganciclovir Cytomegalovirus prophylaxis in high-risk kidney transplant recipients. 10:1228-37.

HTLV

Kaul DR, et al. Donor screening for Human T-cell lymphotrophic virus ½: changing paradigms for changing testing capacity. 10:207-13.

EBV/PTLD

Nourse JP, et al. Epstein-Barr virus related post-transplant lymphoproliferative disorders: pathogenetic insights for targeted therapy. 11:888-95.

Caillard S, et al. Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas. 12:682-93.

Dharnidharka VR, et al. Associations between EBV serostatus and organ transplant type in PTLD risk: an analysis of the SRTR national registry data in the United States. 12:976-83.

Donor Screening for and Transmission of Blood-borne Viruses

Ellingson K, et al. Estimated risk of Human Immunodeficiiency Virus and Hepatitis C virus infection among potential organ donors from 17 organ procurement organizations in the United States. 11:1201-8.

Kucirka LM, et al. Underutilization of Hepatitis C-positive kidneys for Hepatitis C-positive recipients. 10:1238-46

Ison MG, et al. Transmission of Human Immunodeficiency Virus and Hepatitis C virus from an organ donor to four transplant recipients. 11:1218-25.

Boyarsky BJ, et al. Estimating the potential pool of HIV-infected deceased organ donors in the United States. 11:1209-17.

Humar A, et al. Nucleic acid testing (NAT) of organ donors: Is the ‘best’ test the right test? A consensus conference report. 10:889-99.

Kucirka LM, et al. Risk of window period Hepatitis-C infection in high infectious risk donors: systematic review and meta-analysis. 11:1188-1200.

Kucirka LM, et al. Risk of window period HIV infection in high infectious risk donors: systematic review and meta-analysis. 11:1176-87.

Influenza

Kumar D, et al. Influenza vaccination in the organ transplant recipient: review and summary recommendations. 11:2020-30.

Cordero E, et al. Therapy with m-TOR inhibitors decreases the response to the pandemic influenza A H1N1 vaccine in solid organ transplant recipients. 11:2205-13.

Ng BJH, et al. The impact of pandemic influenza A H1N1 2009 on Australian lung transplant recipients. 11:568-74.

HHV8

Pietrosi G, et al. Primary and reactivated HHV8 infection and disease after liver transplantation: a prospective study. 11:2715-23.

Virtual Issue compiled online 12 June 2012

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  Alloantibodies

Guest Editors: Howard M. Gebel and Robert A. Bray 

Alloantibodies, especially those directed against HLA antigens, are a barrier to long-term solid organ allograft survival. Pretransplant, donor-directed alloantibodies represent a contraindication or, at least, a risk, for transplant, effectively limiting patient access to donor organs. Posttransplant, alloantibodies are associated with episodes of acute and chronic rejection as well as graft loss. Initially, serological methods were used to identify HLA antigens and antibodies. Not only were viable cells required for testing, but the sensitivity and specificity of the assays were suboptimal. These limitations led to the development of alternative approaches for HLA testing. In the early 1990s, advances in molecular biology (specifically the development of the polymerase chain reaction) enabled DNA-based HLA antigen testing to be performed. By the mid-1990s, a cytometry-based technology that interrogated microparticles coated with class I / II histocompatibility antigens or HLA-specific DNA could be used to identify HLA antibodies and antigens, respectively. This methodology revolutionized clinical histocompatibility testing. Multiplexing fluorescence-based solid phase assay technology is now the most commonly used HLA testing platform, simultaneously able to distinguish and analyze up to 100 uniquely coated microparticles.

Currently, HLA antibody specificities (including those to class II antigens) are easily delineated even among the most highly sensitized of patients. Failure to detect an HLA antibody that is present, a common occurrence with serological assays, is a rare event. In turn, the virtual crossmatch (vXM), i.e., the ability to reliably predict donor:recipient compatibility, has become a reality. Another breakthrough, predicated on the ability to define completely a patient’s repertoire of HLA antibodies, was the introduction of a new term, namely calculated PRA (cPRA). cPRA is an assessment of the likelihood of compatibility between any patient and a random donor and is derived from the HLA antigen frequencies of >12,000 HLA typed donors. The combination of vXM and cPRA has had a positive impact on deceased donor organ allocation in the United States.

Living donor transplantation has also benefited from advances in HLA antibody and antigen identification, especially among patients/donors participating in paired kidney donor exchange programs. In addition to the detection of HLA-specific antibody, the amount of donor specific antibodies (DSA) present may be a metric to consider. Although requiring validation, quantification of DSA may be a means to assess pretransplant risk and posttransplant response to therapy for patients undergoing desensitization protocols. While specificity and amount of HLA antibody is important, the functional properties of the antibody, such as the ability to activate complement, may be of equal significance. Solid phase approaches can also be used to monitor the complement activating properties of DSA. While certainly not the complete story, complement activation may be a useful tool able to stratify the risk of DSA. Also on the horizon is the recognition that non-HLA alloantibodies (e.g., anti-endothelial cell antibodies) are risk factors to graft survival and monitoring for such antibodies is on the upsurge.

In summary, HLA antibody testing has occurred at a remarkable pace. The tools now available to detect, identify and, quantify DSA represent the cutting edge of technology, but are not perfect. What will be the next step in this evolution?
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Reviews:
Gebel, HM; Bray, RA; Nickerson, P. Pre-transplant assessment of donor-reactive, HLA-specific antibodies in renal transplantation: Contraindication vs. risk. Am J Transplant 2003; 3(12): 1488-1500.

Jordan, SC; Vo, AA; Peng, A; Toyoda, M; Tyan, D. Intravenous gammaglobulin (IVIG): A novel approach to improve transplant rates and outcomes in highly HLA-sensitized patients. Am J Transplant 2006; 6(3): 459-466. 

Stegall, MD; Dean, PG; Gloor, J. Mechanisms of Alloantibody Production in Sensitized Renal Allograft Recipients. Am J Transplant 2009; 9(5): 998-1005.

Montgomery, RA. Renal Transplantation Across HLA and ABO Antibody Barriers: Integrating Paired Donation into Desensitization Protocols. Am J Transplant 2010; 10(3): 449-457.

Jordan, SC; Toyoda, M; Kahwaji, J; Vo, AA. Clinical Aspects of Intravenous Immunoglobulin Use in Solid Organ Transplant Recipients. Am J Transplant 2011; 11(2): 196-202. 

Racusen, LC; Colvin, RB; Solez, K; Mihatsch, MJ; Halloran, PF; Campbell, PM; Cecka, MJ; Cosyns, JP; Demetris, AJ; Fishbein, MC; Fogo, A; Furness, P; Gibson, IW; Glotz, D; Hayry, P; Hunsickern, LN; Kashgarian, M; Kerman, R; Magil, AJ; Montgomery, R; Morozu. Antibody-mediated rejection criteria - an addition to the Banff 97 Classification of Renal Allograft Rejection. Am J Transplant 2003; 3(6): 708-714.

Takemoto, SK; Zeevi, A; Feng, S; Colvin, RB; Jordan, S; Kobashigawa, J; Kupiec-Weglinski, J; Matas, A; Montgomery, RA; Nickerson, P; Platt, JL; Rabb, H; Thistlethwaite, R; Tyan, D; Delmonico, FL. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant 2004; 4(7): 1033-1041. 

Sis, B; Mengel, M; Haas, M; Colvin, RB; Halloran, PF; Racusen, LC; Solez, K; Baldwin, WM; Bracamonte, ER; Broecker, V; Cosio, F; Demetris, AJ; Drachenberg, C; Einecke, G; Gloor, J; Glotz, D; Kraus, E; Legendre, C; Liapis, H; Mannon, RB; Nankivell, BJ; Nic. Banff 09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working Groups. Am J Transplant 2010; 10(3): 464-471.

Archdeacon, P; Chan, M; Neuland, C; Velidedeoglu, E; Meyer, J; Tracy, L; Cavaille-Coll, M; Bala, S; Hernandez, A; Albrecht, R. Summary of FDA Antibody-Mediated Rejection Workshop. Am J Transplant 2011; 11(5): 896-906. 

Virtual Crossmatching/cPRA

Bray, RA; Nolen, JDL; Larsen, C; Pearson, T; Newell, KA; Kokko, K; Guasch, A; Tso, P; Mendel, JB; Gebel, HM. Transplanting the highly sensitized patient: The Emory Algorithm. Am J Transplant 2006; 6(10): 2307-2315.

Bielmann, D; Hoenger, G; Lutz, D; Mihatsch, MJ; Steiger, J; Schaub, S. Pretransplant risk assessment in renal allograft recipients using virtual crossmatching. Am J Transplant 2007; 7(3): 626-632.

Cecka, JM. Calculated PRA (CPRA): The New Measure of Sensitization for Transplant Candidates. Am J Transplant 2010; 10(1): 26-29.

Cecka, JM; Kucheryavaya, AY; Reinsmoen, NL; Leffell, MS. Calculated PRA: Initial Results Show Benefits for Sensitized Patients and a Reduction in Positive Crossmatches. Am J Transplant 2011; 11(4): 719-724. 

Ferrari, P; Fidler, S; Wright, J; Woodroffe, C; Slater, P; Van Althuis-Jones, A; Holdsworth, R; Christiansen, FT. Virtual Crossmatch Approach to Maximize Matching in Paired Kidney Donation. Am J Transplant 2011; 11(2): 272-278. 

Graft rejection/graft loss

Girnita, AL; Duquesnoy, R; Yousem, SA; Iacono, AT; Corcoran, TE; Buzoianu, M; Johnson, B; Spichty, KJ; Dauber, JH; Burckart, G; Griffith, BP; McCurry, KR; Zeevi, A. HLA-specific antibodies are risk factors for lymphocytic bronchiolitis and chronic lung allograft dysfunction. Am J Transplant 2005; 5(1): 131-138.

Wahrmann, M; Exner, M; Schillinger, M; Haidbauer, B; Regele, H; Kormoczi, GF; Horl, WH; Bohmig, GA. Pivotal role of complement-fixing HLA alloantibodies in presensitized kidney allograft recipients. Am J Transplant 2006; 6(5): 1033-1041. 

Sis, B; Campbell, PM; Mueller, T; Hunter, C; Cockfield, SM; Cruz, J; Meng, C; Wishart, D; Solez, K; Halloran, PF. Transplant glomerulopathy, late antibody-mediated rejection and the ABCD tetrad in kidney allograft biopsies for cause. Am J Transplant 2007; 7(7): 1743-1752.

Campbell, PM; Salam, A; Ryan, EA; Senior, P; Paty, BW; Bigam, D; McCready, T; Halpin, A; Imes, S; Al Saif, F; Lakey, JRT; Shapiro, AMJ. Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation. Am J Transplant 2007; 7(5): 1242-1248.

Bums, JM; Comell, LD; Perry, DK; Pollinger, HS; Gloor, JM; Kremers, WK; Gandhi, MJ; Dean, PG; Stegall, MD. Alloantibody Levels and Acute Humoral Rejection Early After Positive Crossmatch Kidney Transplantation. Am J Transplant 2008; 12(8): 2684-2694. 

Everly, MJ; Everly, JJ; Arend, LJ; Brailey, P; Susskind, B; Govil, A; Rike, A; Roy-Chaudhury, P; Mogilishetty, G; Alloway, RR; Tevar, A; Woodle, ES. Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft Loss. Am J Transplant 2009; 9(5): 1063-1071.

O'Boyle, PJ; Smith, JD; Danskine, AJ; Lyster, HS; Burke, MM; Banner, NR. De Novo HLA Sensitization and Antibody Mediated Rejection Following Pregnancy in a Heart Transplant Recipient. Am J Transplant 2010; 10(1): 180-183.

Gloor, JM; Winters, JL; Cornell, LD; Fix, LA; DeGoey, SR; Knauer, RM; Cosio, FG; Gandhi, MJ; Kremers, W; Stegall, MD. Baseline Donor-Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney Transplantation. Am J Transplant 2010; 10(3): 582-589. 

Smith, JD; Banner, NR; Hamour, IM; Ozawa, M; Goh, A; Robinson, D; Terasaki, PI; Rose, ML. De Novo Donor HLA-Specific Antibodies after Heart Transplantation Are an Independent Predictor of Poor Patient Survival. Am J Transplant 2011; 11(2): 312-319.

Willicombe, M; Brookes, P; Santos-Nunez, E; Galliford, J; Ballow, A; Mclean, A; Roufosse, C; Cook, HT; Dorling, A; Warrens, AN; Cairns, T; Taube, D. Outcome of Patients with Preformed Donor-Specific Antibodies Following Alemtuzumab Induction and Tacrolimus Monotherapy. Am J Transplant 2011; 11(3): 470-477.

Loupy, A; Hill, GS; Suberbielle, C; Charron, D; Anglicheau, D; Zuber, J; Timsit, MO; Duong, JP; Bruneval, P; Vernerey, D; Empana, JP; Jouven, X; Nochy, D; Legendre, CH. Significance of C4d Banff Scores in Early Protocol Biopsies of Kidney Transplant Recipients with Preformed Donor-Specific Antibodies (DSA). Am J Transplant 2011; 11(1): 56-65.

Non-HLA antibodies

Le Bas-Bernardet, S; Hourmant, M; Coupel, S; Bignon, JD; Soulillou, JP; Charreau, B. Non-HLA-type endothelial cell reactive alloantibodies in pre-transplant sera of kidney recipients trigger apoptosis. Am J Transplant 2003; 3(2): 167-177.

Terasaki, PI; Ozawa, M; Castro, R. Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney graft survival. Am J Transplant 2007; 7(2): 408-415.

Animal models

Smith, RN; Kawai, T; Boskovic, S; Nadazdin, O; Sachs, DH; Cosimi, AB; Colvin, RB. Chronic antibody mediated rejection of renal allografts: Pathological, serological and immunologic features in nonhuman primates. Am J Transplant 2006; 6(8): 1790-1798.

Galvani, S; Auge, N; Calise, D; Thiers, JC; Canivet, C; Kamar, N; Rostaing, L; Abbal, M; Sallusto, F; Salvayre, R; Bohler, T; Zou, Y; Stastny, P; Negre-Salvayre, A; Thomsen, M. HLA Class I Antibodies Provoke Graft Arteriosclerosis in Human Arteries Transplanted into SCID/Beige Mice. Am J Transplant 2009; 9(11): 2607-2614.

Baldwin, WM; Valujskikh, A; Fairchild, RL. Antibody-Mediated Rejection: Emergence of Animal Models to Answer Clinical Questions. Am J Transplant 2010; 10(5): 1135-1142. 

Virtual Issue compiled online 15 Dec 2011

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Costimulation Blockade

Guest Editor: Dr. Allan D. Kirk, MD, PhD

Transplantation has historically been on the front line with regards to the translation of compelling science into clinical tools. Indeed, numerous approaches to therapeutic immune manipulation have debuted in organ transplantation including the first use of a monoclonal antibody in medicine (OKT3), the first use of a humanized antibody (daclizumab), and numerous pathway specific agents such as calcineurin, mTOR and JAK pathway inhibitors. As transplantation has evolved from an experimental curiosity to an robust standardized clinical practice, its appeal as a testing ground for new mechanistic approaches has waned somewhat; outstanding outcomes make arguments in favor of a new treatment paradigm less compelling. Nevertheless, in 2011 with the approval of belatacept, the prevailing standard again has been challenged with a new mechanistic approach to consider, that being costimulation blockade, and in particular CD28-B7 pathway inhibition.

While the CD28-B7 pathway has been exploited in autoimmunity for several years, its manipulation in transplantation represents a substantial change from immunosuppression as usual, and will no doubt require that the clinical investigative engine that has driven transplantation to its current status will need to re-engage to determine the rightful place of this pathway in the transplant armamentarium. It is important to recognize that a substantial amount of our knowledge regarding proper use of the available agents in transplantation has come after the drugs have been in clinical use, through attentive post-approval investigation. Undoubtedly, this will be true for costimulation blockade, and as such, a coalescence of relevant work in this area seems appropriate to prepare the community for the work that lay ahead.

The American Journal of Transplantation (AJT) has been an important platform for novel investigation in costimulation blockade over the past decade, reporting seminal basic observations, translational milestones, and the pivotal clinical studies facilitating belatacept’s approval. This Virtual Issue presents numerous highlights in all of these categories, as well as insightful commentary on the challenges and opportunities related to belatacept’s approval, in a single location for the reader’s convenience. Specific topics of note include the emergence of our mechanistic understanding of costimulation resistant rejection, the initial description of the design and translational vetting of belatacept, and the pivotal phase 3 trials, the BENEFIT and BENEFIT-EXT, the later being the first phase 3 trial specifically addressing the extended criteria donor scenario. These studies are “required reading” for anyone using belatacept.

Beyond reporting the contemporary stories of belatacept’s development, AJT has introduced numerous visions of the future not only of belatacept, with novel trials and experimental uses of the agent, but also with the next generation of costimulatory pathway inhibitors. In this latter category, this issue highlights basic insights into alternative costimulatory pathways, and critical translational descriptions of inhibitors of the CD40:CD154 pathway, a pathway currently being exploited in phase 1 trials in kidney transplantation. These studies are undoubtedly useful as we consider adjuvant therapies to be paired with belatacept and emergence of other agents. In all, it is hoped that this Virtual Issue provides a useful resource for the clinician and scientist interested in the present and future applications of costimulation blockade in transplantation.

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Editorial

D. Farber. Identification and Targeting of Costimulation-Resistant T cells in Renal Transplantation. Am J Transplant 2011; 11(01): 8-9.

R. Ferguson, J. Grinyó, F. Vincenti et al. Immunosuppression with Belatacept-Based, Corticosteroid-Avoiding Regimens in De Novo Kidney Transplant Recipients. Am J Transplant 2011; 11(01): 66-76. 

B. Kaplan. Belatacept: The Promises and Challenges of Belatacept and Costimulatory Blockade. Am J Transplant 2010; 10(03): 441-442. 

Clinical

F. Vincenti , B. Charpentier, Y. Vanrenterghem et al. A phase III study of belatacept-based immunosuppression regimens vs. cyclosporine I renal transplant recipients (BENEFIT study). Am J Transplant 2010; 10(03): 535-546. 

A. Durrbach, J. M. Pestana, T. Pearson et al. A phase III study of belatacept vs cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am J Transplant 2010; 10(03): 547-557. 

D. J. Lo, T. A. Weaver, L. Stempora et al. Selective Targeting of Human Alloresponsive CD8+ Effector Memory T Cells Based on CD2 Expression. Am j Transplant 2011; 11(01), 22-23.

N. Ashman, A. Chapagain, H. Dobbie et al. Belatacept as Maintenance Immunosuppression for Postrenal Transplant de novo Drug-Induced Thrombotic Microangiopathy. Am J Transplant 2009; 9(02): 424-427.

J. A. Bluestone, W. Liu, J. M. Yabu et al. The Effect of Costimulatory and Interleukin 2 Receptor Blockade on Regulatory T Cells in Renal Transplantation. Am J Transplant 2008; 8(10): 2086-2096. 

P. Trzonkowski, M. Zilvetti, S. Chapman et al. Homeostatic Repopulation by CD28−CD8+ T Cells in Alemtuzumab-Depleted Kidney Transplant Recipients Treated With Reduced Immunosuppression. Am J Transplant 2008; 8(02): 338-347. 

Translational

P. Thompson, K. Cardona, M. Russell et al. CD40-Specific Costimulation Blockade Enhances Neonatal Porcine Islet Survival in Nonhuman Primates. Am J Transplant 2011; 11(05): 947-957.

T. Aoyagi, K. Yamashita, T. Suzuki et al. A Human Anti-CD40 Monoclonal Antibody, 4D11, for Kidney Transplantation in Cynomolgus Monkeys: Induction and Maintenance Therapy. Am J Transplant 2009; 9(08): 1732-1741. 

K. Cardona, Z. Milas, E. Strobert, J. Cano et al. Engraftment of Adult Porcine Islet Xenografts in Diabetic Nonhuman Primates Through Targeting of Costimulation Pathways. Am J Transplant 2007; 7(10): 2260-2268. 

L. S. Kean, A. B. Adams, E. Strobert et al. Induction of Chimerism in Rhesus Macaques through Stem Cell Transplant and Costimulation Blockade-Based Immunosuppression. Am J Transplant 2007; 7(02): 320-335. 

C. P. Larsen, S. J. Knechtle, A. Adams, T. Pearson, A. D. Kirk. A New Look at Blockade of T-cell Costimulation: A Therapeutic Strategy for Long-term Maintenance Immunosuppression. Am J Transplant 2006; 6(05): 876-883. 

E. H. Preston, H. Xu, K. K. Dhanireddy et al. IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates. Am J Transplant 2005; 5(05): 1032-1041. 

C. P. Larsen, T. C. Pearson, A. B. Adams et al. Rational Development of LEA29Y (belatacept), a High-Affinity Variant of CTLA4-Ig with Potent Immunosuppressive Properties. Am J Transplant 2005; 5(03): 443-453. 

T. Kawai, H. Sogawa, S. Boskovic et al. CD154 Blockade for Induction of Mixed Chimerism and Prolonged Renal Allograft Survival in Nonhuman Primates. Am J Transplant 2004; 4(09): 1391-1398. 

H. Xu, E. A. Elster, P. J. Blair et al. Effects of Combined Treatment with CD25- and CD154-Specific Monoclonal Antibodies in Non-Human Primate Allotransplantation. Am J Transplant 2003; 3(11): 1350-1354.

Basic

 T. Zhang, S. Fresnay, E. Welty et al. Selective CD28 Blockade Attenuates Acute and Chronic Rejection of Murine Cardiac Allografts in a CTLA-4-Dependent Manner. Am J Transplant 2011; 11(08): 1599-1609. 

M. Morita, M. Fujino, G. Jiang et al. PD-1/B7-H1 Interaction Contribute to the Spontaneous Acceptance of Mouse Liver Allograft. Am J Transplant 2010; 10(01): 40-46. 

W. Truong, J. C. Plester, W. W. Hancock et al. Combined Coinhibitory and Costimulatory Modulation with Anti-BTLA and CTLA4Ig Facilitates Tolerance in Murine Islet Allografts. Am J Transplant 2007; 7(12): 2663-2674. 

M. L. Ford, M. E. Wagener, S. Gangappa et al. Antigenic Disparity Impacts Outcome of Agonism but Not Blockade of Costimulatory Pathways in Experimental Transplant Models. Am J Transplant 2007; 7(06): 1471-1481. 

Y. Wang, H. Dai, Z. Liu et al. Neutralizing IL-7 Promotes Long-Term Allograft Survival Induced by CD40/CD40L Costimulatory Blockade. Am J Transplant 2006; 6(12): 2851-2860. 

S. J. Huddleston, W. S. Hays, A. Filatenkov et al. CD154+ Graft Antigen-Specific CD4+ T Cells are Sufficient for Chronic Rejection of Minor Antigen Incompatible Heart Grafts. Am J Transplant 2006; 6(06): 1312-1319. 

F. Haspot, C. Séveno, A.-S. Dugast et al. Anti-CD28 Antibody-Induced Kidney Allograft Tolerance Related to Tryptophan Degradation and TCR− Class II− B7+ Regulatory Cells. Am J Transplant 2005; 5(10): 2339-2348. 

S. Bigenzahn, P. Blaha, Z. Koporc et al. The Role of Non-Deletional Tolerance Mechanisms in a Murine Model of Mixed Chimerism with Costimulation Blockade. Am J Transplant 2005; 5(06): 1237-1247. 

W. Li, X. X. Zheng, C. S. Kuhr, J. D. Perkins. CTLA4 Engagement is Required for Induction of Murine Liver Transplant Spontaneous Tolerance. Am J Transplant 2005; 5(05): 978-986. 

S. E. Sandner, M. R. Clarkson, A. D. Salama. Mechanisms of Tolerance Induced by Donor-Specific Transfusion and ICOS-B7h Blockade in a Model of CD4+ T-Cell-Mediated Allograft Rejection. Am J Transplat 2005; 5(01): 31-39. 

A. B. Adams, N. Shirasugi, T. R. Jones et al. Conventional Immunosuppression is Compatible with Costimulation Blockade-Based, Mixed Chimerism Tolerance Induction. Am J Transplant 2003; 3(07): 895-901. 

A. D. Salama, X. Yuan, A. Nayer et al. Interaction Between ICOS-B7RP1 and B7-CD28 Costimulatory Pathways in Alloimmune Responses In Vivo. Am J Transplant 2003; 3(04): 390-395. 

A. Valujskikh, B. Pantenburg, P. S. Heeger. Primed Allospecific T Cells Prevent the Effects of Costimulatory Blockade on Prolonged Cardiac Allograft Survival in Mice. Am J Transplant 2002; 2(06): 501-509. 

Virtual Issue compiled online 7 Oct 2011

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 Kidney Transplantation


Guest Editor: Dr. Bruce Kaplan

This virtual issue of American Journal of Transplantation is devoted to some of the most important topics and observations in kidney transplantation published in AJT over the last five years. In a field this broad, where numerous issues are addressed, there is no way to do justice to every topic nor important paper. It is hoped that this collection of papers will serve as a cohesive sampling of studies and reviews in certain specific topics. The papers chosen represent highly cited and downloaded articles. In doing this, we realize that many excellent papers could not be included.

While antibody-mediated rejection is covered in a separate virtual issue, the topic of anti HLA antibodies is one of great importance. New data seems to implicate anti HLA antibodies in over 50% of all kidney graft loss. The issue of transplantation of patients in the presence of preformed donor specific anti HLA antibodies has gained growing interest. Controversy regarding the best “desensitization” regimes is ongoing. In this issue, we look at several groups’ results utilizing plasmapheresis and IVIg. The issue of adjunctive agents such as Bortezomib is in its infancy. The papers chosen indicate both a need for better understanding of how to prevent long term antibody damage and also to better assess the efficacy and safety of new agents.
The topic of protocol biopsies is another controversial area. Many clinicians utilize protocol biopsies for clinical decisions while others argue that a kidney without clinical dysfunction may yield pathology findings that are associated but not causally related to permanent allograft injury. While the use of protocol biopsies as a research tool is indisputable, its clinical utility needs to be further delineated.

Belatacept is the first biologic agent to be utilized as a maintenance immunosuppressive agent. The BENEFIT study offers intriguing results that remind the readers that these agents are complex and even the best performed studies leave a number of questions unanswered regarding the long term safety and efficacy of any new agent in development. JAK inhibitors and other small molecules cited in this issue indicate the difficulties in defining reliable surrogate end points as well as the need for defining exact effect/safety relationship.

BK nephropathy and BK viremia have become an unfortunate everyday problem. Immunosuppressive reduction seems the key intervention outcome. These papers offer some associative contributions of this observation.

Finally, organ allocation issues remain one of the most controversial areas in the field. The ongoing discussions between a utilitarian approach and an egalitarian approach offer insights into the evaluation of limited resources of the broader field of medicine. While this is a small sampling of the last five years, it is hoped that it will spark future thought and study.

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P. Singh, B. W. Colombe, C. Doria, G. C. Francos, A. M. Frank. A Pitfall in the Current Kidney Allocation Process Using Calculated PRA(CPRA) in Patients Undergoing Desensitization. Am J Transplant 2010; 10(08):1947.

K. Setoguchi, H. Ishida, H. Shimmura, T. Shimizu, H. Shirakawa, K. Omoto et al. Analysis of Renal Transplant Protocol Biopsies in ABO-Incompatible Kidney Transplantation. Am J Transplant 2010; 8(01):86-94.

R. Sberro-Soussan, J. Zuber, C. Suberbielle-Boissel, S. Candon, F. Martinez, R. Snanoudj et al. Bortezomib as the Sole Post-Renal Transplantation Desensitization Agent Does Not Decrease Donor-Specific Anti-HLA Antibodies. Am J Transplant 2010: 10(03); 681-686. 

Bum Soon Choi, Mi Jung Shin, Suk Joon Shin, Young Soo Kim, Yeong Jin Choi, Yong-Soo Kim et al. Clinical Significance of an Early Protocol Biopsy in Living-Donor Renal Transplantation: Ten-Year Experience at a Single Center. Am J Transplant 2005; 5(06): 1354-1360. 

Denis Glotz, Corinne Antoine, Pierre Julia, Caroline Suberbielle-Boissel, Samir Boudjeltia, Rabah Fraoui et al. Desensitization and Subsequent Kidney Transplantation of Patients Using Intravenous Immunoglobulins (IVIg). Am J Transplant 2002; 2(08): 758-760. 

Wilfried Gwinner, Sylvia Suppa, Michael Mengel, Ludwig Hoy, Hans H. Kreipe, Hermann Haller, Anke Schwarz. Early Calcification of Renal Allografts Detected by Protocol Biopsies: Causes and Clinical Implications. Am J Transplant 2005; 5(08): 1934-1941.   

E. J. Ramos, H. S. Pollinger, M. D. Stegall, J. M. Gloor, A. Dogan, J. P. Grande. The Effect of Desensitization Protocols on Human Splenic B-Cell Populations In Vivo. Am J Transplant 2007; 7(02): 402-407.

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W. Gwinner, K. Hinzmann, U. Erdbruegger, I. Scheffner, V. Broecker, B. Vaske et al. Acute Tubular Injury in Protocol Biopsies of Renal Grafts: Prevalence, Associated Factors and Effect on Long-Term Function. Am J Transplant 2008; 8(08): 1684-1693. 

Ron Shapiro, Parmjeet Randhawa, Mark L. Jordan, Velma P. Scantlebury, Carlos Vivas, Ashok Jain et al. An Analysis of Early Renal Transplant Protocol Biopsies – the High Incidence of Subclinical Tubulitis. Am J Transplant 2001; 1(01): 47-50. 

M. Mengel, J. R. Chapman, F. G. Cosio, M. W. Cavaillé-Coll, H. Haller, P. F. Halloran et al. Protocol Biopsies in Renal Transplantation: Insights into Patient Management and Pathogenesis. Am J Transplant 2007; 7(03): 512-517.

B. J. Nankivell, J. R. Chapman. The Significance of Subclinical Rejection and the Value of Protocol Biopsies. Am J Transplant 2006; 6(09): 2006-2012.

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A. Durrbach, J. M. Pestana, T. Pearson, F. Vincenti, V. D. Garcia, J. Campistol et al. A Phase III Study of Belatacept Versus Cyclosporine in Kidney Transplants from Extended Criteria Donors (BENEFIT-EXT Study). Am J Transplant 2010; 10(03): 547-557.

F. Vincenti, B. Charpentier, Y. Vanrenterghem, L. Rostaing, B. Bresnahan, P. Darji et al. A Phase III Study of Belatacept-based Immunosuppression Regimens versus Cyclosporine in Renal Transplant Recipients (BENEFIT Study). Am J Transplant 2010; 10(03): 535-546.

G. Chen, P. P.W. Luke, H. Yang, L. Visser, H. Sun, B. Garcia et al. Anti-CD45RB Monoclonal Antibody Prolongs Renal Allograft Survival in Cynomolgus Monkeys. Am J Transplant 2007; 7(01): 27-37.

N. Ashman, A. Chapagain, H. Dobbie, M. J. Raftery, M. T. Sheaff, M. M. Yaqoob. Belatacept as Maintenance Immunosuppression for Postrenal Transplant de novo Drug-Induced Thrombotic Microangiopathy. Am J Transplant 2009; 9(02): 424-427.

S. Busque, J. Leventhal, D. C. Brennan, S. Steinberg, G. Klintmalm, T. Shah et al. Calcineurin-Inhibitor-Free Immunosuppression Based on the JAK Inhibitor CP-690,550: A Pilot Study in De Novo Kidney Allograft Recipients. Am J Transplant 2009; 9(08): 1936-1945.

K. L. Hardinger, M. J. Koch, D. J. Bohl, G. A. Storch, D. C. Brennan. BK-Virus and the Impact of Pre-Emptive Immunosuppression Reduction: 5-Year Results. Am J Transplant 2010; 10(02): 407-415. 

E. Bernhoff, T. J. Gutteberg, K. Sandvik, H. H. Hirsch, C. H. Rinaldo. Cidofovir Inhibits Polyomavirus BK Replication in Human Renal Tubular Cells Downstream of Viral Early Gene Expression. Am J Transplant 2008; 8(07): 1413-1422.

Cinthia B. Drachenberg, John C. Papadimitriou, Hans H. Hirsch, Ravinder Wali, Clinton Crowder, Joseph Nogueira et al. Histological Patterns of Polyomavirus Nephropathy: Correlation with Graft Outcome and Viral Load. Am J Transplant 2004; 4(12): 2082–2092.

Daniel C. Brennan, Irfan Agha, Daniel L. Bohl, Mark A. Schnitzler, Karen L. Hardinger, Mark Lockwood et al. Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction. Am J Transplant 2005; 5(03): 582–594.

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Barbara A. Bresnahan, Christopher P. Johnson, Matthew J. McIntosh, Donald Stablein, Sundaram Hariharan. A Comparison Between Recipients Receiving Matched Kidney and Those Receiving Mismatched Kidney from the Same Cadaver Donor. Am J Transplant 2002; 2(04): 366–372.

J. J. Curtis. Ageism and Kidney Transplantation. Am J Transplant 2006; 6(06): 1264–1266.

Eric P. Cohen, John D. Rosendale, Christine J. H. Bong, Sundaram Hariharan. Benefit of Child-to-Parent Kidney Donation. Am J Transplant 2003; 3(07): 865–872.

R. A. Wolfe, K. P. McCullough, D. E. Schaubel, J. D. Kalbfleisch, S. Murray, M. D. Stegall, A. B. Leichtman. Calculating Life Years from Transplant (LYFT): Methods for Kidney and Kidney-Pancreas Candidates. Am J Transplant 2008; 8(04): 997–1011.

Y. J. Lee, S. U. Lee, S. Y. Chung, B. H. Cho, J. Y. Kwak, C. M. Kang et al. Clinical Outcomes of Multicenter Domino Kidney Paired Donation. Am J Transplant 2009; 9(10): 2424–2428.

Bruce Kaplan, Herwig-Ulf Meier-Kriesche. Death After Graft Loss: An Important Late Study Endpoint in Kidney Transplantation. Am J Transplant 2002; 2(10): 970-974.

Scott L. Nyberg, Arthur J. Matas, Margaret Rogers, William S. Harmsen, Jorge A. Velosa, Timothy S. Larson et al. Donor Scoring System for Cadaveric Renal Transplantation. Am J Transplant 2001; 1(02): 162–170.

D. A. Gerber, C. J. Arrington, S. E. Taranto, T. Baker, R. S. Sung. DonorNet and the Potential Effects on Organ Utilization. Am J Transplant 2010; 10(04): 1081–1089.

Virtual Issue compiled online 10 Aug 2010
 

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Antibody-Mediated Rejection (ABMR)

 
Guest Editors: Drs. Philip F. Halloran and Michael Mengel

Antibody-mediated rejection (ABMR) is increasingly recognized as one of the biggest challenges in organ transplantation. This virtual issue presents a sample of articles addressing ABMR issues selected from many other articles of interest in AJT on the basis of citation rates and download rates, reflecting impact on the transplantation community. With the exception of liver, ABMR phenotypes probably contribute to late loss of many organ transplants and islet transplants. ABMR can be subtle or explosive, and presents in two main variants: early onset in presensitized persons, often with positive crossmatches; and late insidious onset, usually with de novo anti HLA, particularly anti class II.

The diagnostic criteria for ABMR are undergoing a dynamic re-examination in all organ transplants, recognizing that C4d staining may be the tip of the iceberg. The majority of late kidney graft loss after biopsy for clinical indications is due to ABMR, but much of it is missed because it is C4d negative1, explaining the high incidence of transplant glomerulopathy in failing kidneys2. It seems likely that C4d negative ABMR in kidney transplants is often misdiagnosed as CNI toxicity. The search for a new understanding of ABMR focuses on studies of animal models, HLA antibodies, histopathology and molecular changes in biopsies, and the response to therapy.

Animal models: While ABMR is difficult to evoke in most animal models, primate transplant models do develop features of ABMR3-5, and help to define the temporal history3. However, a caveat in interpreting these reports is that some of the pathology could reflect effects of concomitant T cell mediated rejection.

The HLA antibody phenotype. The association of post transplant HLA antibodies with late kidney graft failure has been important to the recognition of ABMR6;7. But many patients with DSA have no phenotype8, emphasizing that the need to predict which antibodies will produce harm. The quantity of antibody is associated with the probability of pathogenicity9. The ability of HLA antibodies to activate complement fixation has been explored10.

The histopathology phenotypes of kidney transplant biopsies.

While ABMR was described before C4d staining, the C4d test played a key role in understanding the disease. However, the significance of focal versus diffuse C4d remains problematic11. The incidence of C4d staining in protocol biopsies (2%) is lower than indication biopsies12 and its significance in the complete absence of other ABMR lesions is not clear. Loupy et al13 found that protocol biopsies in presensitized patients reveal ABMR lesions as well as C4d positivity, and that these patients are at risk of progression. Interestingly, although ABO blood group incompatible kidneys can do well despite C4d positivity, those with donor specific HLA antibodies can develop ABMR14.

A key element in the pathology of ABMR is capillaritis15, which is associated with glomerulitis and anti HLA. Over time it seems likely that capillaritis will induce peritubular capillary basement membrane multilayering as a time dependent feature of late ABMR16. The main pathway of progression of late ABMR in kidney is the development of transplant glomerulopathy (TG), recognized by double contours (the CG score) and manifest by proteinuria17. Most transplant glomerulopathy has features of ABMR, but a minority do not, raising the question of whether there are other mechanisms or simply different stages18. The spectrum of ABMR in the presensitizied population often includes early ABMR followed by progression to transplant glomerulopathy19.

ABMR phenotypes in biopsies of other organs. ABMR in pancreas and heart transplants shares some features with kidney20;21. Recognition of C4d positive ABMR in pancreas can sometimes lead to successful management21.

Molecular phenotype of ABMR. ABMR is distinct from TCMR but shares inflammation elements with TCMR, including strong IFNG effects, probably reflecting IFNG released from NK cells triggered via their Fc receptors22;23. Homs et al also found FNG effects in biopsies with transplant glomerulopathy24. Many endothelium-associated transcripts are increased in ABMR, including cases that lack C4d staining25. Kidneys with ABMR manifest increased expression of plasmalemmal vesicle-associated protein-1 and caveolin26, and ABMR can induce endothelial expression of phosphoprotein S6 in heart allografts27.

Treatment. Given the complexity of ABMR phenotypes, few true prospective studies of treatment have been reported, and the evidence for efficacy of treatment of ABMR is generally unsatisfactory. The elements usually considered are optimization of immunosuppressive drug management, plasmapheresis (PP), intravenous immunoglobulin (IVIg), rituximab, splenectomy, and experimental agents such as bortexomib and eculizumab. High dose IVIg alone is inferior to Plasmapheresis/IVIg/anti-CD20 as therapy for ABMR28. IVIg administered to presensitized patients29 offers reasonable one-year outcomes, with adequate GFR and a profound decrease in PRA level. PP leads to more reproducible desensitization and lower humoral rejection rates than IVIg30. Splenectomy followed by PP/IVIg may be an effective treatment for reversing severe ABMR31. The C5 inhibitor eculizumab32 has been shown to reduce C5b-C9 (MAC) complex deposition in the allograft of a desensitized patient with ABMR. The proteasome inhibitor bortezomib33 kills some plasma cells, but its efficacy and safety need to be established.


Reference List

1. Einecke G, Sis B, Reeve J, Mengel M, Campbell PM, Hidalgo LG et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant 2009; 9(11):2520-2531.

2. El Zoghby ZM, Stegall MD, Lager DJ, Kremers WK, Amer H, Gloor JM et al. Identifying specific causes of kidney allograft loss. Am J Transplant 2009; 9(3):527-535.

3. Wieczorek G, Bigaud M, Menninger K, Riesen S, Quesniaux V, Schuurman HJ et al. Acute and chronic vascular rejection in nonhuman primate kidney transplantation. Am J Transplant 2006; 6(6):1285-129

4. Smith RN, Kawai T, Boskovic S, Nadazdin O, Sachs DH, Cosimi AB et al. Four stages and lack of stable accommodation in chronic alloantibody-mediated renal allograft rejection in Cynomolgus monkeys. Am J Transplant 2008; 8(8):1662-1672.

5. Smith RN, Kawai T, Boskovic S, Nadazdin O, Sachs DH, Cosimi AB et al. Chronic antibody mediated rejection of renal allografts: pathological, serological and immunologic features in nonhuman primates. Am J Transplant 2006; 6(8):1790-1798.

6. Terasaki PI. Humoral theory of transplantation. Am J Transplant 2003; 3(6):665-673.

7. Terasaki PI, Ozawa M. Predicting kidney graft failure by HLA antibodies: a prospective trial. Am J Transplant 2004; 4(3):438-443.

8. Bartel G, Regele H, Wahrmann M, Huttary N, Exner M, Horl WH et al. Posttransplant HLA alloreactivity in stable kidney transplant recipients-incidences and impact on long-term allograft outcomes. Am J Transplant 2008; 8(12):2652-2660.

9. Issa N, Cosio FG, Gloor JM, Sethi S, Dean PG, Moore SB et al. Transplant glomerulopathy: risk and prognosis related to anti-human leukocyte antigen class II antibody levels. Transplant 2008; 86(5):681-685.

10. Bartel G, Wahrmann M, Exner M, Regele H, Huttary N, Schillinger M et al. In vitro detection of C4d-fixing HLA alloantibodies: associations with capillary C4d deposition in kidney allografts. Am J Transplant 2008; 8(1):41-49.

11. Kedainis RL, Koch MJ, Brennan DC, Liapis H. Focal C4d+ in renal allografts is associated with the presence of donor-specific antibodies and decreased allograft survival. Am J Transplant 2009; 9(4):812-819.

12. Mengel M, Bogers J, Bosmans JL, Seron D, Moreso F, Carrera M et al. Incidence of C4d stain in protocol biopsies from renal allografts: results from a multicenter trial. Am J Transplant 2005; 5(5):1050-1056.

13. Loupy A, Suberbielle-Boissel C, Hill GS, Lefaucheur C, Anglicheau D, Zuber J et al. Outcome of subclinical antibody-mediated rejection in kidney transplant recipients with preformed donor-specific antibodies. Am J Transplant 2009; 9(11):2561-2570.

14. Toki D, Ishida H, Setoguchi K, Shimizu T, Omoto K, Shirakawa H et al. Acute antibody-mediated rejection in living ABO-incompatible kidney transplantation: long-term impact and risk factors. Am J Transplant 2009; 9(3):567-577.

15. Gibson IW, Gwinner W, Brocker V, Sis B, Riopel J, Roberts IS et al. Peritubular capillaritis in renal allografts: prevalence, scoring system, reproducibility and clinicopathological correlates. Am J Transplant 2008; 8(4):819-825.

16. Aita K, Yamaguchi Y, Horita S, Ohno M, Tanabe K, Fuchinoue S et al. Thickening of the peritubular capillary basement membrane is a useful diagnostic marker of chronic rejection in renal allografts. Am J Transplant 2007; 7(4):923-929.

17. Cosio FG, Gloor JM, Sethi S, Stegall MD. Transplant glomerulopathy. Am J Transplant 2008; 8(3):492-496.

18. Sis B, Campbell PM, Mueller T, Hunter C, Cockfield SM, Cruz J et al. Transplant glomerulopathy, late antibody-mediated rejection and the ABCD tetrad in kidney allograft biopsies for cause. Am J Transplant 2007; 7(7):1743-1752.

19. Gloor J, Cosio F, Lager DJ, Stegall MD. The spectrum of antibody-mediated renal allograft injury: implications for treatment. Am J Transplant 2008; 8(7):1367-1373.

20. Rodriguez ER, Skojec DV, Tan CD, Zachary AA, Kasper EK, Conte JV et al. Antibody-mediated rejection in human cardiac allografts: evaluation of immunoglobulins and complement activation products c4d and c3d as markers. Am J Transplant 2005; 5(11):2778-2785.

21. Melcher ML, Olson JL, Baxter-Lowe LA, Stock PG, Posselt AM. Antibody-mediated rejection of a pancreas allograft. Am J Transplant 2006; 6(2):423-428.

22. Mueller TF, Einecke G, Reeve J, Sis B, Mengel M, Jhangri.G. et al. Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am J Transplant 2007; 7(12):2712-2722.

23. Reeve J, Einecke G, Mengel M, Sis B, Kayser N, Kaplan B et al. Diagnosing rejection in renal transplants: A a comparison of molecular- and histopathology-based approaches. Am J Transplant 2009; 9(8):1802-1810.

24. Homs S, Mansour H, Desvaux D, Diet C, Hazan M, Buchler M et al. Predominant Th1 and cytotoxic phenotype in biopsies from renal transplant recipients with transplant glomerulopathy. Am J Transplant 2009; 9(5):1230-1236.

25. Sis B, Jhangri G, Bunnag S, Allanach K, Kaplan B, Halloran PF. Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant 2009; 9(10):2312-2323.

26. Yamamoto I, Horita S, Takahashi T, Tanabe K, Fuchinoue S, Teraoka S et al. Glomerular expression of plasmalemmal vesicle-associated protein-1 in patients with transplant glomerulopathy. Am J Transplant 2007; 7(8):1954-1960.

27. Lepin EJ, Zhang Q, Zhang X, Jindra PT, Hong LS, Ayele P et al. Phosphorylated S6 ribosomal protein: a novel biomarker of antibody-mediated rejection in heart allografts. Am J Transplant 2006; 6(7):1560-1571.

28. Lefaucheur C, Nochy D, Andrade J, Verine J, Gautreau C, Charron D et al. Comparison of combination Plasmapheresis/IVIg/anti-CD20 versus high-dose IVIg in the treatment of antibody-mediated rejection. Am J Transplant 2009; 9(5):1099-1107.

29. Anglicheau D, Loupy A, Suberbielle C, Zuber J, Patey N, Noel LH et al. Posttransplant prophylactic intravenous immunoglobulin in kidney transplant patients at high immunological risk: a pilot study. Am J Transplant 2007; 7(5):1185-1192.

30. Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant 2006; 6(2):346-351.

31. Locke JE, Zachary AA, Haas M, Melancon JK, Warren DS, Simpkins CE et al. The utility of splenectomy as rescue treatment for severe acute antibody mediated rejection. Am J Transplant 2007; 7(4):842-846.

32. Locke JE, Magro CM, Singer AL, Segev DL, Haas M, Hillel AT et al. The Use of Antibody to Complement Protein C5 for Salvage Treatment of Severe Antibody-Mediated Rejection. Am J Transplant 2009; 9(1):231-235.

33. Perry DK, Burns JM, Pollinger HS, Amiot BP, Gloor JM, Gores GJ et al. Proteasome inhibition causes apoptosis of normal human plasma cells preventing alloantibody production. Am J Transplant 2009; 9(1):201-209.

Virtual Issue compiled online 17 Feb 2010

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 Living Liver and Kidney Donation

 

Guest Editor: Dr. Jonathan Bromberg

This virtual issue of the American Journal of Transplantation is focused on living donation. For practical purposes, the articles are restricted to only liver and kidney donation. It would not be an overstatement to say that donation has probably been the number one issue to dominate the field for the last decade, as organ quality and availability determine all activities in transplantation. The breadth of importance and ramifications of donation are reflected in the wide variety of articles and topics that cover this area of interest. Novel sources of donors, such as altruistic, anonymous, and non-directed donation among others are covered in the first section. While considered even unusual a few years ago, many of these sources are now firmly partly of the mainstream of living donation. Exchanges, swaps, chains, and dominos are included in the second section, reflecting the evolution of the field as ever more complex donor and recipient algorithms are implemented, and their attendant ramifications on quality, cost, and outcomes. The third section covers organ utilization and outcomes, with an emphasis on matching the optimal donor with the correct recipient, and comparing deceased to living donor organs. The fourth section covers regulatory issues at the national and local levels, and their influence on donation and outcomes. The fifth section comprises issues relating to the donor and donor safety. The work-up process, safeguards, operative techniques, short term outcomes, and very long term outcomes are major issues the have dominated recent trends. The sixth and last section covers educational issues as they related to donor and family knowledge and attitudes toward donation, and that affects donation rates. These reports should provide the reader with a comprehensive view of issues in living liver and kidney donation, and the diverse paths taken that have moved the field forward.

The articles in this virtual issue have been color coded as follows:

  • Black - renal donation only

  • Blue - both renal and hepatic donation

  • Green - liver donation only

Novel Donor Sources:
 

Twenty-Two Nondirected Kidney Donors: An Update on a Single Center's Experience
C. L. Jacobs, D. Roman, C. Garvey, J. Kahn, A. J. Matas

Altruistic Living Donors: Evaluation for Nondirected Kidney or Liver Donation
M.D. Jendrisak, B. Hong, S. Shenoy, J. Lowell, N. Desai, W. Chapman, A. Vijayan, R.D. Wetzel, M. Smith, J. Wagner, S. Brennan, D. Brockmeier, D. Kappel

Living Anonymous Liver Donation: Case Report and Ethical Justification
L. Wright, K. Ross, S. Abbey, G. Levy, D. Grant

Successful Expansion of the Living Donor Pool by Alternative Living Donation Programs
J. I. Roodnat, J. A. Kal-van Gestel, W. Zuidema, M. A. A. van Noord, J. van de Wetering, J. N. M. IJzermans, W. Weimar

Elective Surgical Patients as Living Organ Donors: A Clinical and Ethical Innovation
G. Testa, P. Angelos, M. Crowley-Matoka, M. Siegler

Kidney Donor Exchanges, Chains, and Dominos:
 

A Comparison of Populations Served by Kidney Paired Donation and List Paired Donation
S. E. Gentry, D. L. Segev, R. A. Montgomery

The Dutch National Living Donor Kidney Exchange Program
M. de Klerk, K. M. Keizer, F. H. J. Claas, M. Witvliet, B. J. J. M. Haase-Kromwijk, W. Weimar

Characterization of Waiting Times in a Simulation of Kidney Paired Donation
D. L. Segev, S. E. Gentry, J. K. Melancon, R. A. Montgomery

Attitudes of Minority Patients with End-Stage Renal Disease Regarding ABO-Incompatible List-Paired Exchanges
P. D. Ackerman, J. R. Thistlethwaite Jr, L. F. Ross

Incompatible Kidney Donor Candidates' Willingness to Participate in Donor-Exchange and Non-directed Donation
A. D. Waterman, E. A. Schenk, A. C. Barrett, B. M. Waterman, J. R. Rodrigue, E. S. Woodle, S. Shenoy, M. Jendrisak, M. Schnitzler

Utilizing List Exchange and Nondirected Donation through 'Chain' Paired Kidney Donations
A. E. Roth, T. Sönmez, M. U. Ünver, F. L. Delmonico, S. L. Saidman

Expanding Kidney Paired Donation Through Participation by Compatible Pairs
S. E. Gentry, D. L. Segev, M. Simmerling, R. A. Montgomery

Successful Three-Way Kidney Paired Donation with Cross-Country Live Donor Allograft Transport
R. A. Montgomery, S. Katznelson, W. I. Bry, A. A. Zachary, J. Houp, J. M. Hiller, S. Shridharani, D. John, A. L. Singer, D. L. Segev

The Roles of Dominos and Nonsimultaneous Chains in Kidney Paired Donation
S. E. Gentry, R. A. Montgomery, B. J. Swihart, D. L. Segev

Asynchronous, Out-of-Sequence, Transcontinental Chain Kidney Transplantation: A Novel Concept
F. K. Butt, H. A. Gritsch, P. Schulam, G. M. Danovitch, A. Wilkinson, J. Del Pizzo, S. Kapur, D. Serur, S. Katznelson, S. Busque, M. L. Melcher, S. McGuire, M. Charlton, G. Hil, J. L. Veale

Clinical Outcomes of Multicenter Domino Kidney Paired Donation
Y. J. Lee, S. U. Lee, S. Y. Chung, B. H. Cho, J. Y. Kwak, C. M. Kang, J. T. Park, D. J. Han, D. J. Kim

Organ Utilization and Outcomes:
 

Living-Donor Liver Transplantation for Hepatoblastoma
M. Kasahara, M. Ueda, H. Haga, H. Hiramatsu, M. Kobayashi, S. Adachi, S. Sakamoto, F. Oike, H. Egawa, Y. Takada, K. Tanaka

Living Donor Liver Transplantation for Biliary Atresia: A Single-Center Experience with First 100 Cases
C.-L. Chen, A. Concejero, C.-C. Wang, S.-H. Wang, C.-C. Lin, Y.-W. Liu, C.-C. Yong, C.-H. Yang, T.-S. Lin, Y.-C. Chiang, B. Jawan, T.-L. Huang, Y.-F. Cheng, H.-L. Eng

Association Between Waiting Times for Kidney Transplantation and Rates of Live Donation
D. L. Segev, S. E. Gentry, R. A. Montgomery

Regional and Racial Disparities in the Use of Live Non-Directed Kidney Donors
D. L. Segev, R. A. Montgomery

Recipient Morbidity After Living and Deceased Donor Liver Tranasplantation: Findings from the A2ALL Retrospective Cohort Study
C. E. Freise, B. W. Gillespie, A. J. Koffron, A. S. F. Lok, T. L. Pruett, J. C. Emond, J. H. Fair, R. A. Fisher, K. M. Olthoff, J. F. Trotter, R. M. Ghobrial, J. E. Everhart

Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation
A. Shaked, R. M. Ghobrial, R. M. Merion, T. H. Shearon, J. C. Emond, J. H. Fair, R. A. Fisher, L. M. Kulik, T. L. Pruett, N. A. Terrault

Resource Utilization of Living Donor Versus Deceased Donor Liver Transplantation Is Similar at an Experienced Transplant Center
J. C. Lai, E. M. Pichardo, J. C. Emond, R. S. Brown Jr.

Organ Donation and Utilization in the United States: 1998–2007
J. E. Tuttle-Newhall, S. M. Krishnan, M. F. Levy, V. McBride, J. P. Orlowski, R. S. Sung

Unique Early Gene Expression Patterns in Human Adult-to-Adult Living Donor Liver Grafts Compared to Deceased Donor Grafts
J. de Jonge, S. Kurian, A. Shaked, K. R. Reddy, W. Hancock, D. R. Salomon, K. M. Olthoff

Regulatory:
 

Incentive Models to Increase Living Kidney Donation: Encouraging Without Coercing
A. K. Israni, S. D. Halpern, S. Zink, S. A. Sidhwani, A. Caplan

Limiting Financial Disincentives in Live Organ Donation: A Rational Solution to the Kidney Shortage
R. S. Gaston, G. M. Danovitch, R. A. Epstein, J. P. Kahn, A. J. Matas, M. A. Schnitzler

Public Attitudes Toward Incentives for Organ Donation: A National Study of Different Racial/Ethnic and Income Groups
L. E. Boulware, M. U. Troll, N. Y. Wang, N. R. Powe

The Association of State and National Legislation with Living Kidney Donation Rates in the United States: A National Study
L. E. Boulware, M. U. Troll, L. C. Plantinga, N. R. Powe

The Evolution and Direction of OPTN Oversight of Live Organ Donation and Transplantation in the United States
R. S. Brown, Jr, R. Higgins, T. L Pruett

Stimulus for Organ Donation: A Survey of the American Society of Transplant Surgeons Membership
J. R. Rodrigue, K. Crist, J. P. Roberts, R. B. Freeman Jr., R. M. Merion, A. I. Reed

Donor Procedures, Outcomes and Safety:
 

Obesity in Living Kidney Donors: Clinical Characteristics and Outcomes in the Era of Laparoscopic Donor Nephrectomy
J. K. Heimbach, S. J. Taler, M. Prieto, F. G. Cosio, S. C. Textor, Y. C. Kudva, G. K. Chow, M. B. Ishitani, T. S. Larson, M. D. Stegall

Laparoscopic Procurement of Kidneys with Multiple Renal Arteries is Associated with Increased Ureteral Complications in the Recipient
J. T. Carter, C. E. Freise, R. A. McTaggart, H. D. Mahanty, S.M. Kang, S. H. Chan, S. Feng, J. P. Roberts, A. M. Posselt

Pre-donation Assessment of Kidneys by Magnetic Resonance Angiography and Venography: Accuracy and Impact on Outcomes
S. A. Ames, M. Krol, K. Nettar, J. P. Goldman, T. M. Quinn, D. M. Herron, A. Pomp, J. S. Bromberg

Long-Term Consequences of Live Kidney Donation Follow-Up in 93% of Living Kidney Donors in a Single Transplant Center
J. Gossmann, A. Wilhelm, H.G. Kachel, J. Jordan, U. Sann, H. Geiger, W. Kramer, E.H. Scheuermann

More on Parental Living Liver Donation for Children with Fulminant Hepatic Failure: Addressing Concerns About Competing Interests, Coercion, Consent and Balancing Acts
A. Spital

Predictive Capacity of Pre-Donation GFR and Renal Reserve Capacity for Donor Renal Function After Living Kidney Donation
M. Rook, H. S. Hofker, W. J. van Son, J. J. Homan van der Heide, R. J. Ploeg, G. J. Navis

Laparoscopic-Assisted Right Lobe Donor Hepatectomy
A.J. Koffron, R. Kung, T. Baker, J. Fryer, L. Clark, M. Abecassis

Cold Ischemia Time and Allograft Outcomes in Live Donor Renal Transplantation: Is Live Donor Organ Transport Feasible?
C. E. Simpkins, R. A. Montgomery, A. M. Hawxby, J. E. Locke, S. E. Gentry, D. S. Warren, D. L. Segev

Evaluating Living Kidney Donors: Relationship Types, Psychosocial Criteria, and Consent Processes at US Transplant Programs
J. R. Rodrigue, M. Pavlakis, G. M. Danovitch, S. R. Johnson, S. J. Karp, K. Khwaja, D. W. Hanto, D. A. Mandelbrot

The Medical Evaluation of Living Kidney Donors: A Survey of US Transplant Centers
D. A. Mandelbrot, M. Pavlakis, G. M. Danovitch, S. R. Johnson, S. J. Karp, K. Khwaja, D. W. Hanto, J. R. Rodrigue

Rescue of a Living Donor with Liver Transplantation
B. Ringe, G. Xiao, D. A. Sass, J. Karam, S. Shang, T. P. Maroney, A. E. Trebelev, S. Levison, A. C. Fuchs, R. Petrucci, A. Ko, M. Gonzalez, J. C. Reynolds, W. C. Meyers

Nephrectomy Elicits Impact of Age and BMI on Renal Hemodynamics: Lower Postdonation Reserve Capacity in Older or Overweight Kidney Donors
M. Rook, R. J. Bosma, W. J. van Son, H. S. Hofker, J. J. Homan van der Heide, P. M. ter Wee, R. J. Ploeg, G. J. Navis

Pregnancy and Birth After Kidney Donation: The Norwegian Experience
A. V. Reisæter, J. Røislien, T. Henriksen, L. M. Irgens, A. Hartmann

Pregnancy Outcomes After Kidney Donation
H. N. Ibrahim, S. K. Akkina, E. Leister, K. Gillingham, G. Cordner, H. Guo, R. Bailey, T. Rogers, A. J. Matas

Education:

Preferences, Knowledge, Communication and Patient-Physician Discussion of Living Kidney Transplantation in African American Families
L. E. Boulware, L. A. Meoni, N. E. Fink, R. S. Parekh, W. H. L. Kao, M. J. Klag, N. R. Powe

Organ Donation Decision: Comparison of Donor and Nondonor Families
J. R. Rodrigue, D. L. Cornell, R. J. Howard

Increasing Live Donor Kidney Transplantation: A Randomized Controlled Trial of a Home-Based Educational Intervention
J. R. Rodrigue, D. L. Cornell, J. K. Lin, B. Kaplan, R. J. Howard

Emigration from the British Isles to Southeastern Spain: A Study of Attitudes Toward Organ Donation
A. Ríos, P. Cascales, L. Martínez, J. Sánchez, N. Jarvis, P. Parrilla, P. Ramírez

Virtual Issue compiled online 2 Feb 2010

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Islet Transplantation Issues

 

Guest Editor: Dr. Jonathan Bromberg

This virtual issue of the AJT is focused on islet transplantation with the emphasis on clinical and translational science. The isolation, assessment, and preservation of viable islets continue to represent major hurdles to clinical success; this is the subject of the first grouping of papers which highlights diverse approaches to solving these problems. The second grouping of manuscripts analyzes various techniques for islet implantation, including different anatomic environments and methods to ameliorate the interaction of islets with blood and complement. Clinical outcomes, complications, and immunosuppression, the core of all clinical transplantation, occupy the next three sections, with an emphasis on novel immunosuppressants, including those that may have a role in xenotransplantation. Novel approaches to imaging islets, employing MRI and PET, are listed in the sixth grouping. The last section compiles a number of reports discussing financial and regulatory issues as important variables that influence the ability to perform these transplants. These reports should provide the reader with a comprehensive view of issues in islet transplantation, and the diverse scientific and intellectual paths that are being taken to move the field forward.

Islet Preparation and Assessment:

A Novel Method for the Assessment of Cellular Composition and Beta-Cell Viability in Human Islet Preparations
H. Ichii, L. Inverardi, A. Pileggi, R. D. Molano, O. Cabrera, A. Caicedo, S. Messinger, Y. Kuroda, P. Berggren, C.Ricordi

Islet Transplantation in Type 1 Diabetes Mellitus Using Cultured Islets and Steroid-Free Immunosuppression: Miami Experience
T. Froud, C. Ricordi, D. A. Baidal, M. M. Hafiz, G. Ponte, P. Cure, A. Pileggi, R. Poggioli, H. Ichii, A. Khan, J. V. Ferreira, A. Pugliese, V. V. Esquenazi, N. S. Kenyon, R. Alejandro

Shipment of Human Islets for Transplantation
H. Ichii, Y. Sakuma, A. Pileggi, C. Fraker, A. Alvarez, J. Montelongo, J. Szust, A. Khan, L. Inverardi, B. Naziruddin, M. F. Levy, G. B. Klintmalm, J. A. Goss, R. Alejandro, C. Ricordi

Improvement of Human Islet Cryopreservation by a p38 MAPK Inhibitor
K. Omori, L. Valiente, C. Orr, J. Rawson, K. Ferreri, I. Todorov, I. H. Al-Abdullah, S. Medicherla, A. A. Potter, G. F. Schreiner, F. Kandeel, Y. Mullen

Glucose-Stimulated Increment in Oxygen Consumption Rate as a Standardized Test of Human Islet Quality
I. R. Sweet, M. Gilbert, S. Scott, I. Todorov, R. Jensen, I. Nair, I. Al-Abdullah, J. Rawson, F. Kandeel, K. Ferreri

Acute Insulin Response to Arginine in Deceased Donors Predicts the Outcome of Human Islet Isolation
T. Hubert, G. Strecker, V. Gmyr, L. Arnalsteen, D. Garrigue, R. Ezzouaoui, R. Caiazzo, G. Dezfoulian, B. Averland, B. Vandewalle, M. C. Vantyghem, J. Kerr-Conte, F. Pattou

Islet Transplant Techniques:
 

Intramuscular Autotransplantation of Pancreatic Islets in a 7-Year-Old Child: A 2-Year Follow-Up
E. Rafael, A. Tibell, M. Rydén, T. Lundgren, L. Sävendahl, B. Borgström, U. Arnelo, B. Isaksson, B. Nilsson, O. Korsgren, J. Permert

Long-Term Survival of Nonhuman Primate Islets Implanted in an Omental Pouch on a Biodegradable Scaffold
D. M. Berman, J. J. O'Neil, L. C. K. Coffey, P. C. J. Chaffanjon, N. M. Kenyon, P. Ruiz Jr, A. Pileggi, C. Ricordi, Norma S. Kenyon

Endoscopic Gastric Submucosal Transplantation of Islets (ENDO-STI): Technique and Initial Results in Diabetic Pigs
G. J. Echeverri, K. McGrath, R. Bottino, H. Hara, E. M. Dons, D. J. van der Windt, B. Ekser, A. Casu, S. Houser, M. Ezzelarab, R. Wagner, M. Trucco, F. G. Lakkis, D. K. C. Cooper

Thrombomodulin Improves Early Outcomes After Intraportal Islet Transplantation
W. Cui, J. T. Wilson, J Wen, J Angsana, Z Qu, C. A. Haller, E. L. Chaikof

Tirofiban and Activated Protein C Synergistically Inhibit the Instant Blood Mediated Inflammatory Reaction (IBMIR) from Allogeneic Islet Cells Exposure to Human Blood
S. Akima, W. J. Hawthorne, E. Favaloro, A. Patel, K. Blyth, Y. Mudaliar, J. R. Chapman, P. J. O'Connell

Long-Term Controlled Normoglycemia in Diabetic Non-Human Primates After Transplantation with hCD46 Transgenic Porcine Islets
D. J. van der Windt, R. Bottino, A. Casu, N. Campanile, C. Smetanka, J. He, N. Murase, H. Hara, S. Ball, B. E Loveland, D. Ayares, F. G. Lakkis, D. K. C. Cooper, M. Trucco

Clinical Outcomes:
 

Quality of Life After Islet Transplantation
R. Poggioli, R. N. Faradji, G. Ponte, A. Betancourt, S. Messinger, D. A. Baidal, T. Froud, C. Ricordi, R. Alejandro

Has Time Come for New Goals in Human Islet Transplantation?
R. Lehmann, G. A. Spinas, W. Moritz, M. Weber

The Clinical Impact of Islet Transplantation
P. Fiorina, A. M. J. Shapiro, C. Ricordi, A. Secchi

Complications:
 

Prevention of Bleeding After Islet Transplantation: Lessons Learned from a Multivariate Analysis of 132 Cases at a Single Institution
P. Villiger, E. A. Ryan, R. Owen, K. O'Kelly, J. Oberholzer, F. Al Saif, T. Kin, H. Wang, I. Larsen, S. L. Blitz, V. Menon, P. Senior, D. L. Bigam, B. Paty, N. M. Kneteman, J. R. T. Lakey, A. M. James Shapiro

Changes in Renal Function after Clinical Islet Transplantation: Four-Year Observational Study
P. A. Senior, M. Zeman, B. W. Paty, E. A. Ryan, A. M. James Shapiro

High Risk of Sensitization After Failed Islet Transplantation
P. M. Campbell, P. A. Senior, A. Salam, K. LaBranche, D. L. Bigam, N. M. Kneteman, S. Imes, A. Halpin, E. A. Ryan, A. M. J. Shapiro

Immunosuppression:
 

Transplantation of Cultured Islets from Two-Layer Preserved Pancreases in Type 1 Diabetes with Anti-CD3 Antibody
B. J. Hering, R. Kandaswamy, J. V. Harmon, J. D. Ansite, S. M. Clemmings, T. Sakai, S. Paraskevas, P. M. Eckman, J. Sageshima, M. Nakano, T. Sawada, I. Matsumoto, H. J. Zhang, D. E. R. Sutherland, J. A. Bluestone

Prolonged Survival of Allogeneic Islets in Cynomolgus Monkeys After Short-Term Anti-CD154-Based Therapy: Nonimmunologic Graft Failure?
M. Koulmanda, R.N. Smith, A. Qipo, G. Weir, H. Auchincloss, T.B. Strom

Antiangiogenic and Immunomodulatory Effects of Rapamycin on Islet Endothelium: Relevance for Islet Transplantation
V. Cantaluppi, L. Biancone, G. Mauriello Romanazzi, F. Figliolini, S. Beltramo, M. S. Ninniri, F. Galimi, R. Romagnoli, A. Franchello, M. Salizzoni, P. Cavallo Perin, C. Ricordi, G. P. Segoloni, G. Camussi

Pretransplant HLA Antibodies Are Associated with Reduced Graft Survival After Clinical Islet Transplantation
P. M. Campbell, A. Salam, E. A. Ryan, P. Senior, B. W. Paty, D. Bigam, T. McCready, A. Halpin, S. Imes, F. Al Saif, J. R. T. Lakey, A. M. J. Shapiro

Engraftment of Adult Porcine Islet Xenografts in Diabetic Nonhuman Primates Through Targeting of Costimulation Pathways
K. Cardona, Z. Milas, E. Strobert, J. Cano, W. Jiang, S. A. Safley, S. Gangappa, B. J. Hering, C. J. Weber, T. C. Pearson, C. P. Larsen

An Anti-CD103 Immunotoxin Promotes Long-Term Survival of Pancreatic Islet Allografts
L. Zhang, S. D. Moffatt-Bruce, A. A. Gaughan, J-J. Wang, A. Rajab, G. A. Hadley

Imaging:
 

Clinical Magnetic Resonance Imaging of Pancreatic Islet Grafts After Iron Nanoparticle Labeling
C. Toso, J.-P. Vallee, P. Morel, F. Ris, S. Demuylder-Mischler, M. Lepetit-Coiffe, N. Marangon, F. Saudek, A. M. James Shapiro, D. Bosco, T. Berney

Improving the Procedure for Detection of Intrahepatic Transplanted Islets by Magnetic Resonance Imaging
M. L. Malosio, A. Esposito, A. Poletti, S. Chiaretti, L. Piemonti, R. Melzi, R. Nano, F. Tedoldi, T. Canu, P. Santambrogio, C. Brigatti, F. De Cobelli, P. Maffi, A. Secchi, A. Del Maschio

Positron Emission Tomography in Clinical Islet Transplantation
O. Eriksson, T. Eich, A. Sundin, A. Tibell, G. Tufveson, H. Andersson, M. Felldin, A. Foss, L. Kyllönen, B. Langstrom, B. Nilsson, O. Korsgren, T. Lundgren

Regulatory/Financial:
 

Are Criteria for Islet and Pancreas Donors Sufficiently Different to Minimize Competition?
Frédéric Ris, Christian Toso, Florence Unno Veith, Pietro Majno, Philippe Morel, José Oberholzer

Islet Xenotransplantation: Are We Really Ready for Clinical Trials?
P. P. M. Rood, D. K. C. Cooper

Financial Issues Constraining the Use of Pancreata Recovered for Islet Transplantation: A White Paper
J. F. Markmann, D. B. Kaufman, C. Ricordi, P. M. Schwab, P. G. Stock

Organ Procurement Organization Compliance with 21 CFR 1271: A Challenge for Allogeneic Pancreatic Islet Cell Transplantation Programs
J. L. Winters, S. A. Tran, D. A. Gastineau, D. J. Padley, P. G. Dean, Y. C. Kudva

Virtual Issue compiled online 20 Jan 2010

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Infectious Disease Issues in Organ Transplantation
 

Guest Editor: Dr. Atul Humar

This virtual issue brings together a collection of papers in the field of transplant infectious diseases. These include original manuscripts published in AJT as well as recent mini-reviews. Transplant ID has witnessed significant advances in the last decade. These have occurred in all areas and encompass basic, translational and clinical research. Morbidity and mortality from certain infections (e.g. CMV) have decreased significantly although new challenges continuously arise. The selected articles highlight some of the recent advances in Transplant ID. For example, molecular diagnostic techniques have revolutionized our approach to common pathogens in transplant recipients and are routinely employed in strategies for the diagnosis, prevention and treatment of common viral pathogens such as CMV and EBV. The modern immunosuppression era has also witnessed the emergence of new pathogens and disease entities such as BK virus associated nephropathy. Transplant programs have readily adapted to these new threats by adopting novel screening and prevention strategies. The changing global epidemiology of infections including the geographic spread of infections (e.g. West Nile virus), the emergence of novel respiratory viruses (novel H1N1 influenza), and others have highlighted the unique susceptibility of transplant recipients to emerging pathogens. It has also become clear that prevention and treatment strategies for common pathogens and disease entities must evolve to match changes in immunosuppression. Despite advances, there is always room for much more progress in a number of areas of transplant ID including donor derived infections, fungal disease, and in the search for new therapies for viruses such as BK virus, EBV, and others. The papers selected here highlight some of the more recent important developments, clinical trials, and reviews that have been published in AJT. We have focused primarily on clinical and translational findings that have direct relevance to the care of the transplant patient.

Update on Immunizations in Solid Organ Transplant Recipients: What Clinicians Need to Know
R. K. Avery, M. Michaels

BK Virus Infection in Transplant Recipients: An Overview and Update
P. Randhawa, D. C. Brennan

Pandemic Influenza and Its Implications for Transplantation
D. Kumar, A. Humar

A Practical Guide to the Management of HCV Infection Following Liver Transplantation
K. Watt, B. Veldt, M. Charlton

Prevention of Infection in Adult Travelers After Solid Organ Transplantation
Camille Nelson Kotton, Edward T. Ryan, Jay A. Fishman

Herpes Simplex and Varicella Zoster Viruses: Forgotten but Not Gone
G. G. Miller, J. S. Dummer

Epstein-Barr Virus: Evasive Maneuvers in the Development of PTLD
Andrew L. Snow, Olivia M. Martinez

Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients
A. Åsberg, A. Humar, H. Rollag, A. G. Jardine, H. Mouas, M. D. Pescovitz, D. Sgarabotto, M. Tuncer, I. L. Noronha, A. Hartmann

Cell-Mediated Immunity to Predict Cytomegalovirus Disease in High-Risk Solid Organ Transplant Recipients
D. Kumar, S. Chernenko, G. Moussa, I. Cobos, O. Manuel, J. Preiksaitis, S. Venkataraman, A. Humar

Polyfunctional Cytomegalovirus-Specific CD4+ and pp65 CD8+ T Cells Protect Against High-Level Replication After Liver Transplantation
G. Nebbia, F. M. Mattes, C. Smith, E. Hainsworth, J. Kopycinski, A. Burroughs, P. D. Griffiths, P. Klenerman, V. C. Emery

Prophylactic Versus Preemptive Oral Valganciclovir for the Management of Cytomegalovirus Infection in Adult Renal Transplant Recipients
J. A. Khoury, G. A. Storch, D. L. Bohl, R. M. Schuessler, S. M. Torrence, M. Lockwood, M. Gaudreault-Keener, M. J. Koch, B. W. Miller, K. L. Hardinger, M. A. Schnitzler, D. C. Brennan

Improvement in Long-Term Renal Graft Survival due to CMV Prophylaxis with Oral Ganciclovir: Results of a Randomized Clinical Trial
V. Kliem, L. Fricke, T. Wollbrink, M. Burg, J. Radermacher, F. Rohde

Interlaboratory Comparison of Cytomegalovirus Viral Load Assays
X. L. Pang, J. D. Fox, J. M. Fenton, G. G. Miller, A. M. Caliendo, J. K. Preiksaitis

Valganciclovir Dosing According to Body Surface Area and Renal Function in Pediatric Solid Organ Transplant Recipients
W. Vaudry, R. Ettenger, P. Jara, G. Varela-Fascinetto, M. R. Bouw, J. Ives, R. Walker

Long-Term Outcomes of CMV Disease Treatment with Valganciclovir Versus IV Ganciclovir in Solid Organ Transplant Recipients
A. Åsberg, A. Humar, A. G. Jardine, H. Rollag, M. D. Pescovitz, H. Mouas, A. Bignamini, H. Töz, I. Dittmer, M. Montejo, A. Hartmann

Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction
Daniel C. Brennan, Irfan Agha, Daniel L. Bohl, Mark A. Schnitzler, Karen L. Hardinger, Mark Lockwood, Stephanie Torrence, Rebecca Schuessler, Tiffany Roby, Monique Gaudreault-Keener, Gregory A. Storch

Kidney Transplant Function and Histological Clearance of Virus Following Diagnosis of Polyomavirus-Associated Nephropathy (PVAN)
H. M. Wadei, A. D. Rule, M. Lewin, A. S. Mahale, H. A. Khamash, T. R. Schwab, J. M. Gloor, S. C. Textor, M. E. Fidler, D. J. Lager, T. S. Larson, M. D. Stegall, F. G. Cosio, M. D. Griffin

Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney Recipients
F. Ginevri, A. Azzi, H. H. Hirsch, S. Basso, I. Fontana, M. Cioni, S. Bodaghi, V. Salotti, A. Rinieri, G. Botti, F. Perfumo, F. Locatelli, P. Comoli

Screening to Prevent Polyoma Virus Nephropathy in Kidney Transplantation: A Cost Analysis
F. Smith, R. Panek, B. A. Kiberd

Estimated Benefits of Transplantation of Kidneys from Donors at Increased Risk for HIV or Hepatitis C Infection
E. J. Schweitzer, E. N. Perencevich, B. Philosophe, S. T. Bartlett

Viral Nucleic Acid Testing (NAT) and OPO-Level Disposition of High-Risk Donor Organs
L. M. Kucirka, C. Alexander, R. Namuyinga, C. Hanrahan, R. A. Montgomery, D. L. Segev

Zygomycosis In Solid Organ Transplant Recipients in a Tertiary Transplant Center and Review of the Literature
N. G. Almyroudis, D. A. Sutton, P. Linden, M. G. Rinaldi, J. Fung, and S. Kusne

Voriconazole Prophylaxis in Lung Transplant Recipients
S. Husain, D. L. Paterson, S. Studer, J. Pilewski, M. Crespo, D. Zaldonis, K. Shutt, D. L. Pakstis, A. Zeevi, B. Johnson, E. J. Kwak, K. R. McCurry

Immunogenicity of Pneumococcal Vaccine in Renal Transplant Recipients—Three Year Follow-up of a Randomized Trial
D. Kumar, B. Welsh, D. Siegal, M. Hong Chen, A. Humar

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients
J. Scharpé, P. Evenepoel, B. Maes, B. Bammens, K. Claes, A. D. Osterhaus, Y. Vanrenterghem, W. E. Peetermans

Ganciclovir and Acyclovir Reduce the Risk of Post-Transplant Lymphoproliferative Disorder in Renal Transplant Recipients
Donnie P. Funch, Alexander M. Walker, Gary Schneider, Najat J. Ziyadeh, Mark D. Pescovitz

Interlaboratory Comparison of Epstein-Barr Virus Viral Load Assays
J. K. Preiksaitis, X. L. Pang, J. D. Fox, J. M. Fenton, A. M. Caliendo, G. G. Miller

HIV-Infected Liver and Kidney Transplant Recipients: 1- and 3-Year Outcomes
M. E. Roland, B. Barin, L. Carlson, L. A. Frassetto, N. A. Terrault, R. Hirose, C. E. Freise, L. Z. Benet, N. L. Ascher, J. P. Roberts, B. Murphy, M. J. Keller, K. M. Olthoff, E. A. Blumberg, K. L. Brayman, S. T. Bartlett, C. E. Davis, J. M. McCune, B. M. Bredt, D. M. Stablein, P. G. Stock

Thymoglobulin-Associated Cd4+ T-Cell Depletion and Infection Risk in HIV-Infected Renal Transplant Recipients
J.T. Carter, M.L. Melcher, L.L. Carlson, M.E. Roland, P.G. Stock

Virtual Issue compiled online 4 Jan 2010

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Presenting the United States Organ Transplantation data report 2010

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