Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

31 July 2009

Evaluation of the genetic background of standard-immunosuppressant-related toxicity in a cohort of 200 paediatric renal allograft recipients – a retrospective study

Ryszard Grenda, Sylwester Prokurat, Andrzej Ciechanowicz, Barbara Piątosa, Piotr Kaliciński

Ann Transplant 2009; 14(3): 18-24 :: ID: 880536

Abstract

Background: Immunosuppressant toxicity is a limiting factor for the efficacy and safety of long-term therapy. Whether it stems solely from drug exposure, remains unclear.
Material/Methods: Overall, 207 children and adolescents at the mean age of 11±4.4, with primary renal allograft were analyzed. Immunosuppression regimens included CsA or TAC, combined with AZA or MMF and steroids. Drug-specific toxicities were diagnosed by renal biopsy and/or clinical criteria. Genotyping for MDR1, CYP3A5, IL1B, IL1RN, IL-6, IL-10, MCP-1, TGFB1, CCR5, VEGF and TNF-alpha gene polymorphisms was performed with the use of PCR and PCR-RFLP techniques.
Results: Nephrotoxicity was seen in 38.5% of patients treated with CsA and 29.5% - with TAC, while gingival hypertrophy was observed in 28% of CsA patients. Myelotoxicity was found in 3% of AZA-treated and 6.4% of MMF-treated patients. No significant correlation was seen between the patient's age, gender, type of pre-transplantation dialysis, donor age, graft origin or cold ischemia time, and the occurrence of drug-related toxicity. For CNIs, the drug exposure and the duration of treatment did not prove of significance either. TAC associated nephrotoxicity correlated with the CCR5 gene polymorphism, as the wt/∆32 genotype was found in 21% of patients with no detected toxicity (p<0.041) and in none of the nephrotoxicity cases. The presence of this genotype was also associated with significantly better graft function at 1 year post-transplant (GFR 115.104±28.40 vs 86.434±29.96; p=0.022). An association was seen between the MMF-induced myelotoxicity and the TNF-alpha G(-308)A polymorphism (p<0.005), but the MMF exposure was higher in patients who developed toxicity.
Conclusions: Genetic background should be regarded one of the risk factors for immunosuppressant related toxicity in renal transplantation.

Keywords: genetic background, renal transplantation

Add Comment 0 Comments

In Press

Original article  

Steroid Use in ABO-Incompatible Kidney Transplants: Withdrawal vs Maintenance

Ann Transplant In Press; DOI: 10.12659/AOT.947747  

Original article  

Intra-Arterial Contrast-Enhanced Ultrasound for Transcatheter Thrombolysis in Post-Transplant Hepatic Arter...

Ann Transplant In Press; DOI: 10.12659/AOT.947500  

Original article  

Early Atropine Protocol Enhances Dobutamine Stress Echocardiography in End-Stage Liver Disease: A Practical...

Ann Transplant In Press; DOI: 10.12659/AOT.950166  

Most Viewed Current Articles

15 Aug 2023 : Review article   7,349

Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

DOI :10.12659/AOT.939750

Ann Transplant 2023; 28:e939750

03 Jan 2023 : Original article   7,205

Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...

DOI :10.12659/AOT.938467

Ann Transplant 2023; 28:e938467

16 May 2023 : Original article   7,029

Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...

DOI :10.12659/AOT.939258

Ann Transplant 2023; 28:e939258

28 May 2024 : Original article   6,629

Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflura...

DOI :10.12659/AOT.943281

Ann Transplant 2024; 29:e943281

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358