Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath.
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.


METHODS
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.
Shapiro
Ron
R
Thomas E Starzl Transplantation Institute, the University of Pittsburgh Medical Center, PA 15213, USA.
Basu
Amit
A
Tan
Henkie
H
Gray
Edward
E
Kahn
Akhtar
A
Randhawa
Parmjeet
P
Murase
Noriko
N
Zeevi
Adriana
A
Girnita
Alin
A
Metes
Diana
D
Ness
Roberta
R
Bass
Debra C
DC
Demetris
Anthony J
AJ
Fung
John J
JJ
Marcos
Amadeo
A
Starzl
Thomas E
TE
D000704:Analysis of Variance; D015703:Antigens, CD / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000276:immunology*; D000074301:CD52 Antigen; D016009:Chi-Square Distribution; D016572:Cyclosporine / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology*; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care; D020123:Sirolimus / Q000008:administration & dosage; D016019:Survival Analysis; D016559:Tacrolimus / Q000008:administration & dosage; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000961:Antilymphocyte Serum; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus