Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.
BACKGROUND
The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction.


METHODS
Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months).


RESULTS
There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08).


CONCLUSIONS
This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.
Stevens
R Brian
RB
Department of Surgery, University of Nebraska Medical Center, Omaha, NE 68198-3285, USA. rbstevens@unmc.edu
Mercer
David F
DF
Grant
Wendy J
WJ
Freifeld
Alison G
AG
Lane
James T
JT
Groggel
Gerald C
GC
Rigley
Theodore H
TH
Nielsen
Kathleen J
KJ
Henning
Megan E
ME
Skorupa
Jill Y
JY
Skorupa
Anna J
AJ
Christensen
Kecia A
KA
Sandoz
John P
JP
Kellogg
Anna M
AM
Langnas
Alan N
AN
Wrenshall
Lucile E
LE
D000328:Adult; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011817:Rabbits; D020123:Sirolimus / Q000627:therapeutic use; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use; D014184:Transplantation, Homologous
D000961:Antilymphocyte Serum; D020123:Sirolimus; D016559:Tacrolimus