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 KalicińskiAnn 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
In Press
08 Mar 2024 : Original article
Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persisten...Ann Transplant In Press; DOI: 10.12659/AOT.943532
14 Mar 2024 : Original article
Impact of Blood Products Transfusion on Patients in the Immediate Post-Lung Transplant Period: A Cohort StudyAnn Transplant In Press; DOI: 10.12659/AOT.943652
14 Mar 2024 : Case report
Treatment of Cavernous Transformation of Portal Vein Caused by Hepatic Cystic Echinococcosis Using Ex Vivo ...Ann Transplant In Press; DOI: 10.12659/AOT.942358
15 Mar 2024 : Review article
Approaches and Challenges in the Current Management of Cytomegalovirus in Transplant Recipients: Highlighti...Ann Transplant In Press; DOI: 10.12659/AOT.941185
Most Viewed Current Articles
05 Apr 2022 : Original article
Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver TransplantationDOI :10.12659/AOT.935604
Ann Transplant 2022; 27:e935604
12 Jan 2022 : Original article
Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...DOI :10.12659/AOT.934738
Ann Transplant 2022; 27:e934738
22 Nov 2022 : Original article
Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...DOI :10.12659/AOT.937988
Ann Transplant 2022; 27:e937988
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860