Pediatric Nephrology

, Volume 25, Issue 5, pp 965–969

Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics

  • Sandrine Leroy
  • Arnaud Isapof
  • Sonia Fargue
  • May Fakhoury
  • Albert Bensman
  • Georges Deschênes
  • Evelyne Jacqz-Aigrain
  • Tim Ulinski
Brief Report

DOI: 10.1007/s00467-009-1402-8

Cite this article as:
Leroy, S., Isapof, A., Fargue, S. et al. Pediatr Nephrol (2010) 25: 965. doi:10.1007/s00467-009-1402-8

Abstract

Tacrolimus is known to potentially lead to adverse events in recipients with diarrhoea and/or calcium channel blocker (CCB) co-administration. We report a renal transplant recipient who suffered from severe nephrotoxicity related to a toxic tacrolimus trough concentration in both conditions, diarrhoea and CCB co-administration, and with genotyped CYP3A system and P-glycoprotein (P-gp) polymorphisms. To our knowledge, this is the first case to be investigated for such polymorphisms. Clinicians should be reminded of the possibility of highly increased levels of tacrolimus in situations of diarrhoea and/or co-administration of CCBs. It also highlights the key role in tacrolimus pharmacokinetics of the CYP3A system and P-gp polymorphisms, and their influence in high-risk situations when enzyme activity is already affected by enterocyte damage due to diarrhoea and CCB competition.

Keywords

Calcium channel blockerCytochrome P450DiarrhoeaP-glycoproteinPolymorphismsRenal transplantTacrolimus

Abbreviations

CCB

Calcium channel blocker

CYP

Cytochrome P450

MDR1

Multi-drug resistance 1

P-gp

P-glycoprotein

SNP

Single nucleotide polymorphism

Copyright information

© IPNA 2010

Authors and Affiliations

  • Sandrine Leroy
    • 1
  • Arnaud Isapof
    • 1
  • Sonia Fargue
    • 2
    • 3
  • May Fakhoury
    • 4
  • Albert Bensman
    • 1
  • Georges Deschênes
    • 5
  • Evelyne Jacqz-Aigrain
    • 4
  • Tim Ulinski
    • 1
    • 6
  1. 1.Department of Pediatric NephrologyArmand-Trousseau Hospital, AP-HP and University Paris VIParisFrance
  2. 2.Department of BiologyUniversity College LondonLondonUK
  3. 3.Department of Pediatric Nephrology—Reference Centre for Rare Renal DiseasesFemme Mère Enfant Hospital, University of LyonLyonFrance
  4. 4.Department of Pediatric Pharmacology—Pharmacogenetics and Clinical Investigation Center—CIC9202Robert-Debré Hospital, AP-HPParisFrance
  5. 5.Department of Pediatric NephrologyRobert-Debré Hospital, AP-HPParisFrance
  6. 6.Inserm UMR S938Université Pierre et Marie CurieParisFrance