PMID- 9721802
OWN - NLM
STAT- MEDLINE
DCOM- 19980902
LR  - 20190713
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 66
IP  - 3
DP  - 1998 Aug 15
TI  - Monitored high-dose azathioprine treatment reduces acute rejection episodes after 
      renal transplantation.
PG  - 334-9
AB  - BACKGROUND: Azathioprine (AZA) is widely used in organ transplantation. Common 
      practice is to adjust dose according to body weight only, despite documented 
      pharmacokinetic variability. The purpose of this study was to investigate whether 
      high-dose AZA treatment monitored by 6-thioguanine nucleotides (6-TGN) levels 
      reduces the incidence of rejection episodes in renal transplantation without a 
      corresponding increase in myelotoxicity. METHODS: Patients receiving 
      cyclosporine, steroids, and AZA were randomized into either the low-dose AZA 
      group (3 mg/kg on day 0, then 2 mg/kg/day the first week and 1 mg/kg/day 
      thereafter) or the high-dose AZA group. In the latter, AZA was started at 5 
      mg/kg/day and then adjusted to keep 6-TGN concentrations (measured twice weekly) 
      between 100 and 200 pmol/8 x 10(8) RBCs. RESULTS: A total of 360 transplant 
      recipients were included in the final analysis. The cumulative incidence of first 
      rejection episodes was reduced by 21%, from 62.8% in the low-dose group to 49.4% 
      in the high-dose group (difference: 13.3%; 95% confidence interval: 3.2-23.5). 
      Similar results were found in subgroups according to HLA-DR match. The 6-TGN 
      concentration was significantly higher in the high-dose AZA group during the 
      first month, and the reduction in rejection episodes was achieved in the same 
      period. A larger proportion of patients in the high-dose group had nadir white 
      blood cell count below 2.0 x 10(9) leukocytes/L (13.3% vs. 4.4%; difference: 
      8.9%; confidence interval: 3.1-14.7). CONCLUSIONS: High-dose AZA therapy in a 
      triple-drug regimen, monitored by 6-TGN, will keep myelotoxicity within 
      acceptable limits with the benefit of a reduction in acute rejection episodes.
FAU - Bergan, S
AU  - Bergan S
AD  - Institute of Clinical Biochemistry, Department of Clinical Pharmacology, National 
      Hospital, University of Oslo, Norway.
FAU - Rugstad, H E
AU  - Rugstad HE
FAU - Bentdal, O
AU  - Bentdal O
FAU - Sodal, G
AU  - Sodal G
FAU - Hartmann, A
AU  - Hartmann A
FAU - Leivestad, T
AU  - Leivestad T
FAU - Stokke, O
AU  - Stokke O
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Guanine Nucleotides)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Thionucleotides)
RN  - 15867-02-4 (6-thioguanylic acid)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Azathioprine/*administration & dosage/adverse effects/pharmacokinetics
MH  - Bone Marrow/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - *Drug Monitoring
MH  - Drug Therapy, Combination
MH  - Female
MH  - Graft Rejection/*drug therapy/immunology
MH  - Guanine Nucleotides/blood
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage/adverse 
      effects/pharmacokinetics
MH  - *Kidney Transplantation/immunology
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - Neutrophils/drug effects/immunology
MH  - Thionucleotides/blood
EDAT- 1998/08/29 00:00
MHDA- 1998/08/29 00:01
CRDT- 1998/08/29 00:00
PHST- 1998/08/29 00:00 [pubmed]
PHST- 1998/08/29 00:01 [medline]
PHST- 1998/08/29 00:00 [entrez]
AID - 10.1097/00007890-199808150-00010 [doi]
PST - ppublish
SO  - Transplantation. 1998 Aug 15;66(3):334-9. doi: 10.1097/00007890-199808150-00010.