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

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, diarrho...

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Bibliographic Details
Published in:Pediatric nephrology (Berlin, West) West), 2010-05, Vol.25 (5), p.965-969
Main Authors: Leroy, Sandrine, Isapof, Arnaud, Fargue, Sonia, Fakhoury, May, Bensman, Albert, Deschênes, Georges, Jacqz-Aigrain, Evelyne, Ulinski, Tim
Format: Article
Language:English
Subjects:
Acute Kidney Injury - chemically induced
Acute Kidney Injury - enzymology
Acute Kidney Injury - genetics
Adolescent
ATP Binding Cassette Transporter, Sub-Family B
ATP-Binding Cassette, Sub-Family B, Member 1 - genetics
ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism
Brief Report
Calcium Channel Blockers - adverse effects
Calcium channels
Competition
Complications and side effects
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Diarrhea
Diarrhea - complications
Drug interaction
Drug Interactions
Drug Monitoring
Drug therapy
Enterocytes
Enzymes
Gene polymorphism
Genetic Predisposition to Disease
Humans
Immunosuppressive Agents - adverse effects
Immunosuppressive Agents - pharmacokinetics
Kidney Transplantation
Kidneys
Male
Medicine
Medicine & Public Health
Nephrology
Organ transplant recipients
P-Glycoprotein
Pediatrics
Pharmacogenetics
Pharmacokinetics
Phenotype
Polymorphism, Single Nucleotide
Risk Factors
Risk groups
Tacrolimus
Tacrolimus - adverse effects
Tacrolimus - pharmacokinetics
Transplantation
Transplants & implants
Urology
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Summary: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.
ISSN:0931-041X
1432-198X
DOI:10.1007/s00467-009-1402-8