PMID- 35757730
OWN - NLM
STAT- MEDLINE
DCOM- 20220628
LR  - 20220716
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Case Report: Azathioprine: An Old and Wronged Immunosuppressant.
PG  - 903012
LID - 10.3389/fimmu.2022.903012 [doi]
LID - 903012
AB  - Mycophenolate rapidly substituted azathioprine (AZA) in transplant 
      immunosuppression regimens since the 1990s, when early clinical trials indicated 
      better outcomes, although opposite results were also observed. However, none of 
      these trials used the well-established optimization methods for AZA dosing, 
      namely, thiopurine methyltransferase pharmacogenetics combined with monitoring of 
      the thiopurine metabolites 6-thioguanine nucleotides (6-TGN) and 
      6-methylmercaptopurine (6-MMP). Resistance to optimize AZA therapy remains today 
      in transplant therapy, despite the fact that thiopurine metabolite testing is 
      being used by other medical disciplines with evident improvement in clinical 
      results. In a previous analysis, we found that active 6-TGN metabolites were not 
      detectable in about 30% of kidney transplant patients under continuous use of 
      apparently adequate azathioprine dosage, which demonstrates the need to monitor 
      these metabolites for therapeutic optimization. Two of four case studies 
      presented here exemplifies this fact. On the other hand, some patients have toxic 
      6-TGN levels with a theoretically appropriate dose, as seen in the other two case 
      studies in this presentation, constituting one more important reason to monitor 
      the AZA dose administered by its metabolites. This analysis is not intended to 
      prove the superiority of one immunosuppressant over another, but to draw 
      attention to a fact: there are thousands of patients around the world receiving 
      an inadequate dose of azathioprine and, therefore, with inappropriate 
      immunosuppression. This report is also intended to draw attention, to clinicians 
      using thiopurines, that allopurinol co-therapy with AZA is a useful therapeutic 
      pathway for those patients who do not adequately form active thioguanine 
      metabolites.
CI  - Copyright (c) 2022 Chocair, Neves, Mohrbacher, Neto, Sato, Oliveira, Barbosa, 
      Bales, Silva, Cuvello-Neto and Duley.
FAU - Chocair, Pedro R
AU  - Chocair PR
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Neves, Precil Diego Miranda de Menezes
AU  - Neves PDMM
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Mohrbacher, Sara
AU  - Mohrbacher S
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Neto, Maurilio Pacheco
AU  - Neto MP
AD  - School of Medicine, Sapucai Valley University, Pouso Alegre, Brazil.
FAU - Sato, Victor A H
AU  - Sato VAH
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Oliveira, Erico S
AU  - Oliveira ES
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Barbosa, Leonardo V
AU  - Barbosa LV
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Bales, Alessandra M
AU  - Bales AM
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - da Silva, Fagner Pereira
AU  - da Silva FP
AD  - Nursing Service, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil.
FAU - Cuvello-Neto, Americo L
AU  - Cuvello-Neto AL
AD  - Internal Medicine and Nephrology Service, Hospital Alemao Oswaldo Cruz, Sao 
      Paulo, Brazil.
FAU - Duley, John A
AU  - Duley JA
AD  - School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia.
LA  - eng
PT  - Case Reports
PT  - Research Support, Non-U.S. Gov't
DEP - 20220610
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Immunosuppressive Agents)
RN  - FTK8U1GZNX (Thioguanine)
RN  - MRK240IY2L (Azathioprine)
SB  - IM
MH  - *Azathioprine
MH  - Enzyme Inhibitors
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects
MH  - *Kidney Transplantation
MH  - Thioguanine/therapeutic use
PMC - PMC9226564
OTO - NOTNLM
OT  - 6-TGN
OT  - allopurinol
OT  - azathioprine
OT  - metabolites
OT  - mycophenolate
OT  - renal transplant
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/06/28 06:00
MHDA- 2022/06/29 06:00
PMCR- 2022/01/01
CRDT- 2022/06/27 04:31
PHST- 2022/03/23 00:00 [received]
PHST- 2022/05/12 00:00 [accepted]
PHST- 2022/06/27 04:31 [entrez]
PHST- 2022/06/28 06:00 [pubmed]
PHST- 2022/06/29 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.903012 [doi]
PST - epublish
SO  - Front Immunol. 2022 Jun 10;13:903012. doi: 10.3389/fimmu.2022.903012. eCollection 
      2022.