Kidney Paired Donation: A single center approach to increase living donor transplantation

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 Bingaman A, Kapturczak M, Murphey C, Wright F.

http://www.ncbi.nlm.nih.gov/pubmed/21696052

(Excerpt) "The kidney paired donation KPD program at Methodist Specialty and Transplant Hospital (MSTH) in San Antonio has significantly increased access to transplantation for patients with incompatible living donors, especially for disadvantaged group such as the highly sensitized population of repeat transplant patients and multiparous women. The KPD program increased overall live donor activity allowing MSTH to become the largest living donor kidney transplant center in the nation in 2009. In 2010, MSTH performed 193 living donor kidney transplants with 68 (35%) transplants from the KPD program. This demonstrates that an effective KPD program can significantly benefit difficult patients and increase transplant access and activity in a single center setting."

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A Summary of Bortezomib Use in Transplantation Across 29 Centers.

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Despite the substantial effects and promise of bortezomib-based regimens, there is still much to be learned. Finding an effective approach to removing antibodies is an ultimate goal. At this time it seems that bortezomib is a key element in improving the treatment for rejection (both acute and chronic) and in desensitization. In regard to such clinical outcomes as achieving transplant and stabilizing allograft function, bortezomib-based regimens have shown in the cases presented here to have a high success rate, albeit lower with desensitization and chronic rejection than with acute rejection. Bortezomib, even in combination regimens, has also shown a good safety profile, although side effects such a thrombocytopenia, gastrointestinal disturbances, and even peripheral neuropathy have been reported in transplant patients following treatment. In addition, bortezomib's safety regarding viral reactivation of cytomegalovirus, Epstein Barr virus, and BK virus are not clearly known, therefore precautions must be taken (especially in combination regimens). Moving forward, continual data collection and trials will be needed to answer questions about bortezomib. Hopefully, this effort and future efforts to collectively gather data and collaborate with a common goal of treating antibodies will lead us to improved long term allograft survival.

 

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Impact of Donor-Specific HLA Antibodies (DSA) in Transplant, a Review of the Literature Published In the Last Three Years

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Author: Hugo Kaneku, MD

This chapter summarizes some of the recent findings published on the role in organ transplantation of HLA antibodies, and--more important--donor-specific HLA antibodies. The negative impact of both, preformed and de novo DSA is now better recognized in recipients of kidney, heart, lung, liver, pancreas, islet cells and bone marrow transplants. An appropriate design of a schedule to monitor HLA antibodies may identify patients at higher risk for immunological events earlier and allow interventions to avoid later graft loss. The value of strategies like preemptive treatment of antibodies and the use of new agents like bortezomib and eculizumab are of interest and need further investigation.

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Clinical Management of Renal Transplant Patients with Donor-Specific Alloantibody: The State of the Art

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http://www.ncbi.nlm.nih.gov/pubmed/21696048

Author: Mark Stegall, M.D.

(Excerpt) "Donor-specific alloantibody is increasingly recognized as a major problem in renal transplantation. Whether present prior to transplantation or developing de novo after transplantation, the presence of DSA is a significant risk factor for premature graft loss.  The past decade has seen the development of several novel therapeutic approaches to these patients.  Paired donor programs now provide the possibility of either avoiding DSA completely or providing a donor against whom the recipient has much less antibody.  Novel desensitization protocols have allowed successful transplantation of patients once considered untransplantable.  Newer, more sensitive alloantibody detection assays have demonstrated that donor specific alloantibody (DSA) is a much more common than previously realized both pre and post-transplant.  This review outlines our current understanding of alloantibody at various stages of transplantation and endeavors to assess the current treatment approaches to these difficult clinical problems.  At the request of the editors, I also will address the challenges involved in clinical trial design in this area."

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Using HLA antibody detection, monitoring, and treatment to improve long-term allograft survival

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Author: Matthew Everly, PharmD

http://www.ncbi.nlm.nih.gov/pubmed/21696049

The evidence supporting HLA antibodies as a biomarker in transplant is substantial. It is becoming more clear that these patients represent a new phenotype of patient that is at the highest risk to rapidly progress to chronic damage. Therefore early detection of these high risk patients through serial screening is necessary. Additionally, once patients develop DSA positivity, IgG subclass testing may indicate how eminent his/her graft failure ensue. Moving forward, we should focus monitoring and treating at first detection of persistent antibodies. This may be the only reasonable way to have significant impact on long-term allograft survival.

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An Update on Antibody Reduction and Rejection Reversal following Bortezomib Use: A report of 52 cases across 10 centers

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Based on the analysis of the 52 patient cases submitted for the Antibody Treatment Report of Clinical Transplants 2010, there is growing evidence that bortezomib is a viable option for antibody mediated rejection (AMR).

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A "New" Road to Tolerance: Clonal Deletion and Drug Added When Needed (DAWN)

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Terasaki PI, Everly ML, Kaneku H, Hoshino J, Vanikar AV, Patel HV, Shah PR, Trivedi HL.
 

We propose clonal deletion— immunization followed by deletion —as a "new" way to achieve tolerance. Immunization of a donor results in specific stimulation of a clone of cells, which can then be killed by various agents, leaving the patient otherwise immunologically normal. The theory of clonal deletion is supported by experimental evidence as well as earlier experiences with kidney transplants and donor - specific transfusions. To date, 22 patients who underwent clonal deletion have been surviving for 1.5 to 2.5 years with only low -dose prednisone. In addition, those patients who required conventional immunosuppressive drugs were treated with the new Drugs Added When Needed (DAWN) protocol. With DAWN as a tactic ready for intervention, and by using antibodies to monitor the completeness of clonal deletion, we assure that patients are subjected to the minimal amount of drugs on a personalized basis. We suggest that risks involved in testing this new procedure are small and the benefits immeasurable.

For access to complete text pdf:Terasaki_ClonalDeletion_CT2010

 

Clinical Transplants 2009: Bortezomib Case Reports in Solid Organ Transplant

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Center

Authors

Organ(s)

Cases No.

Page No.

Baylor College of Medicine

R Raghavan, A Jeroudi, K Achkar, W Suki, AO Gaber, R Knight, G Land, S Dilioglou, S Patel, A Abdellatif

Kidney

1

 

Beth Israel Deaconess Medical Center

M Pavlakis

Kidney

2

 

Cedars-Siani Heart Institute

JK Patel, MJ Everly, M Kittleson, JA Kobashigawa

Heart

1

 

Charité-Universitätsmedizin Berlin

N Lachmann, M Schutz, K Budde, C Schonemann, J Waiser

Kidney

3

 

Huazhong University of Science and Technology, Tongi Medical College

L Zhu, Z Lin, Y Xiang, S Liu, G Chen

Kidney

1

 

Institut de Transplantation et de Recherche en Transplantation

HL Mai, A Cesbron, S Brouard, G Blancho, D Cantarovich, J Dantal, M Hourmant, M Lino, A Meurette, M Gosselin, O Abadie, J Soulillou, M Giral

Kidney

3

 

Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán

S Leyva, LA Marino-Vazquez, J Reyes, O Vega, N Uribe-Uribe, J Alberu, LE Morales-Buenrostro

Kidney

6

 

Johns Hopkins University

BE Lonze, NN Dagher, CE Simpkins, AL Singer, DL Segev, AA Zachary, RA Montgomery

Kidney, Hematologic

4

 

King Faisal Specialist Hospital & Research Center

K Al Meshari

Kidney

1

 

Leiden University Medical Center

S Heidt, DL Roelen, M Vergunst, IIN Doxiadis, FHJ Claas, A Mulder

-

In vitro

 

LifeLink Health Care Institute

M Weston, M Rolfe, T Haddad, M Lopez-Cepero

Heart, Lung

4

 

Massachusetts General Hospital

W Wong, R Lee, SL Saidman, RN Smith, E Zorn

Kidney

3

 

Mayo Clinic- Arizona

K Hamawi, RL Heilman, MJ Mazur, HA Chakkera, DC Mulligan, AA Moss, KL Mekeel, KS Reddy

Kidney

7

 

Medical University of Vienna

M Wahrmann, M Haidinger, J Drach, R Geyeregger, Z Kikic,R Raab, MD Saemann, GA Bohmig

Kidney

2

 

Santa Casa Hospital

J Neumann, S Schio, H Tarrasconi, A Bortolotto, C Costa, T Machuca, S Camargo, L Sanchez, T Michelon, R Canabarro, H Sporleder, S Fernandes, J Camargo, F, Perin, J Felicetti

Lung

5

 

Temple University

I Lee, S Constantinescu, A Gillespie, A Swami, M Birkenbach, S Leech, P Silva, A Karachristos, JA DAller, NM Sifontis

Kidney

1

 

The Thomas E. Starzl Transplantation Institute

R Shapiro, A Basu, A Zeevi, J Lunz, M Mapara, P Randhawa, C Morgan, HP Tan, V Sharma

Kidney

1

 

Université Paris Descartes & Hôpital Necker

R Sberro-Soussan, J Zuber, C Suberbielle-Boissel, C Legendre

Kidney

4

 

University of Alabama

V Kumar, S Elkins, RS Gaston, MB Prendergast, V Reddy, WJ Cook, PW Sanders

Kidney

1

 

University of Cincinnati Medical Center

A Govil, C Walsh, A Tevar, R Alloway, P Roy-Chaudhury, G Mogilishetty, GE Wall, P Brailey, A Girnita, ES Woodle

Kidney, Pancreas

7

 

University of Colorado at Denver

JE Cooper, AC Wiseman, L Chan

Kidney, Pancreas

3

 

University of Maryland

W Manitpisitku, N Wilson, M Cooper, C Gurk-Turner, H Hurley, F Rasetto, D KuKuruga, R Barth, B Philosophe

Kidney

1

 

University of Miami

ER Island, IM Gonzalez-Pinto, H Tsai, P Ruiz, P Tryphonopoulos, ML Gonzalez, JP Solano, M Rossique, G Selvaggi, A Tekin, LJ Smith, AG Tzakis

Multivisceral

(Pediatric)

1

 

University of Michigan

LJ Stuckey, M Kamoun, A Wadhwa, M Samaniego, C Bartos, J Berry, R Mahidhara, AC Chang, KMChan

Lung

1

 

University of Minnesota

PM Eckman, M Thorsgard, D Maurer, Y Kim, RR Alloway, ES Woodle

Heart

1

 

University of Missouri-Kansas City

KL Hardinger, K Alford, D Murillo

Kidney

2

 

University of Wisconsin-Madison

A Djamali, BL Muth, J Torrealba, D Bloom, KM Miller, D Lorentzen, HW Sollinger, JD Pirsch

Kidney, Pancreas

2

 

Washington University in St. Louis

R Boothpur, S Torrence, DC Brennan

Hematologic

1

 

Weill Cornell Medical College

Report #1:MJ Aull, S Saal, D Dadhania, C Hartono, S Kapur

Report #2:C Hartono, M Lubetzky,MJ Aull, S Saal, J Figueiro, S Kapur, D Dadhania

Kidney

3

 

Total

 

-

72

-