BACKGROUND: Multiple drug immunosuppression has allowed the near elimination of rejection, but without commensurate improvements in longterm graft survival and at the cost of quality of life. We have suggested that transplantation outcomes can be improved by modifying the timing and dosage of immunosuppression to facilitate natural mechanisms of alloengraftment and acquired tolerance. STUDY DESIGN: Two therapeutic principles were applied for kidney transplantation: pretransplant recipient conditioning with antilymphoid antibody preparations (Thymoglobulin [Sangstat] or Campath [ILEX Pharmaceuticals]), and minimal posttransplant immunosuppression with tacrolimus monotherapy including "spaced weaning" of maintenance doses when possible. The results in Thymoglobulin- (n = 101) and Campath-pretreated renal transplantation recipients (n = 90) were compared with those in 152 conventionally immunosuppressed recipients in the immediately preceding era. RESULTS: Spaced weaning was attempted in more than 90% of the kidney transplant recipients after pretreatment with both lymphoid-depleting agents, and is currently in effect in two-thirds of the survivors. Although there was a much higher rate of acute rejection in the Thymoglobulin-pretreated recipients than in either the Campath-pretreated or historic control recipients, patient and graft survival in both lymphoid depletion groups is at least equivalent to that of historic control patients. In the Thymoglobulin-conditioned patients for whom followups are now 24 to 40 months, chronic allograft nephropathy (CAN) progressed at the same rate as in historic control patients. Selected patients on weaning developed donor-specific nonreactivity. CONCLUSIONS: After lymphoid depletion, kidney transplantation can be readily accomplished under minimal immunosuppression with less dependence on late maintenance immunosuppression and a better quality of life. Campath was the more effective agent for pretreatment. Guidelines for spaced weaning need additional refinement.
BACKGROUND: Multiple drug immunosuppression has allowed the near elimination of rejection, but without commensurate improvements in longterm graft survival and at the cost of quality of life. We have suggested that transplantation outcomes can be improved by modifying the timing and dosage of immunosuppression to facilitate natural mechanisms of alloengraftment and acquired tolerance. STUDY DESIGN: Two therapeutic principles were applied for kidney transplantation: pretransplant recipient conditioning with antilymphoid antibody preparations (Thymoglobulin [Sangstat] or Campath [ILEX Pharmaceuticals]), and minimal posttransplant immunosuppression with tacrolimus monotherapy including "spaced weaning" of maintenance doses when possible. The results in Thymoglobulin- (n = 101) and Campath-pretreated renal transplantation recipients (n = 90) were compared with those in 152 conventionally immunosuppressed recipients in the immediately preceding era. RESULTS: Spaced weaning was attempted in more than 90% of the kidney transplant recipients after pretreatment with both lymphoid-depleting agents, and is currently in effect in two-thirds of the survivors. Although there was a much higher rate of acute rejection in the Thymoglobulin-pretreated recipients than in either the Campath-pretreated or historic control recipients, patient and graft survival in both lymphoid depletion groups is at least equivalent to that of historic control patients. In the Thymoglobulin-conditioned patients for whom followups are now 24 to 40 months, chronic allograft nephropathy (CAN) progressed at the same rate as in historic control patients. Selected patients on weaning developed donor-specific nonreactivity. CONCLUSIONS: After lymphoid depletion, kidney transplantation can be readily accomplished under minimal immunosuppression with less dependence on late maintenance immunosuppression and a better quality of life. Campath was the more effective agent for pretreatment. Guidelines for spaced weaning need additional refinement.
Authors: Thomas E Starzl; Noriko Murase; Kareem Abu-Elmagd; Edward A Gray; Ron Shapiro; Bijan Eghtesad; Robert J Corry; Mark L Jordan; Paulo Fontes; Tim Gayowski; Geoffrey Bond; Velma P Scantlebury; Santosh Potdar; Parmjeet Randhawa; Tong Wu; Adriana Zeevi; Michael A Nalesnik; Jennifer Woodward; Amadeo Marcos; Massimo Trucco; Anthony J Demetris; John J Fung Journal: Lancet Date: 2003-05-03 Impact factor: 79.321
Authors: Diana Metes; Alison Logar; William A Rudert; Adriana Zeevi; Jennifer Woodward; Anthony J Demetris; Kareem Abu-Elmagd; Bijan Eghtesad; Ron Shapiro; John J Fung; Massimo Trucco; Thomas E Starzl; Noriko Murase Journal: Hum Immunol Date: 2003-08 Impact factor: 2.850
Authors: Thomas E Starzl; Noriko Murase; Anthony J Demetris; Massimo Trucco; Kareem Abu-Elmagd; Edward A Gray; Bijan Eghtesad; Ron Shapiro; Amadeo Marcos; John J Fung Journal: Transplantation Date: 2004-03-27 Impact factor: 4.939
Authors: Allan D Kirk; Douglas A Hale; Roslyn B Mannon; David E Kleiner; Steven C Hoffmann; Robert L Kampen; Linda K Cendales; Douglas K Tadaki; David M Harlan; S John Swanson Journal: Transplantation Date: 2003-07-15 Impact factor: 4.939
Authors: Brian J Nankivell; Richard J Borrows; Caroline L-S Fung; Philip J O'Connell; Richard D M Allen; Jeremy R Chapman Journal: N Engl J Med Date: 2003-12-11 Impact factor: 91.245
Authors: Stuart J Knechtle; John D Pirsch; John H Fechner; Bryan N Becker; Andreas Friedl; Robert B Colvin; Lauralynn K Lebeck; L Thomas Chin; Yolanda T Becker; Jon S Odorico; Anthony M D'Alessandro; Munci Kalayoglu; Majed M Hamawy; Huaizhong Hu; Debra D Bloom; Hans W Sollinger Journal: Am J Transplant Date: 2003-06 Impact factor: 8.086
Authors: Ron Shapiro; Mark L Jordan; Amit Basu; Velma Scantlebury; Santosh Potdar; Henkie P Tan; Edward A Gray; Parmjeet S Randhawa; Noriko Murase; Adriana Zeevi; Anthony J Demetris; Jennifer Woodward; Amadeo Marcos; John J Fung; Thomas E Starzl Journal: Ann Surg Date: 2003-10 Impact factor: 12.969
Authors: Ron Shapiro; Amit Basu; Henkie P Tan; Claire Morgan; Vivek Sharma; Deanna Blisard; Parmjeet S Randhawa; Igor Dvorchik; Jerry McCauley; Demetrius Ellis; J Wallis Marsh; Steven Webber; Geoffrey Kurland; Kenneth McCurry; Kareem Abu-Elmagd; George Mazariegos; Thomas E Starzl Journal: Transplantation Date: 2008-05 Impact factor: 4.939
Authors: Daniel R Getts; Sushma Shankar; Emily M L Chastain; Aaron Martin; Meghann Teague Getts; Kathryn Wood; Stephen D Miller Journal: Immunotherapy Date: 2011-07 Impact factor: 4.196
Authors: A Basu; J L Falcone; H P Tan; D Hassan; I Dvorchik; K Bahri; N Thai; P S Randhawa; A Marcos; T E Starzl; R Shapiro Journal: Transplant Proc Date: 2007 Jan-Feb Impact factor: 1.066
Authors: Bénédicte Sautenet; Allison Tong; Karine E Manera; Jeremy R Chapman; Anthony N Warrens; David Rosenbloom; Germaine Wong; John Gill; Klemens Budde; Lionel Rostaing; Lorna Marson; Michelle A Josephson; Peter P Reese; Timothy L Pruett; Camilla S Hanson; Donal O'Donoghue; Helen Tam-Tham; Jean-Michel Halimi; Jenny I Shen; John Kanellis; John D Scandling; Kirsten Howard; Martin Howell; Nick Cross; Nicole Evangelidis; Philip Masson; Rainer Oberbauer; Samuel Fung; Shilpa Jesudason; Simon Knight; Sreedhar Mandayam; Stephen P McDonald; Steve Chadban; Tasleem Rajan; Jonathan C Craig Journal: Transplantation Date: 2017-08 Impact factor: 4.939