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A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection
Published on: February 2, 2022
Mutagenicity of immunosuppressive medications among renal transplant recipients
Thomas Rath1, Vilma Oliveira-Frick
1Department of Nephrology and Transplantation Medicine, Medical Clinics III, Westpfalz-Klinikum, Kaiserslautern, Germany. trath@westpfalz-klinikum.de
Background:
Immunosuppressive therapy is essential for patients after renal transplantation, but it may have mutagenic side effects. The frequency of micronuclei (MN) assessed by the cytokinesis block assay is well established in the diagnosis of DNA damage.
Methods:
We examined 79 patients before and after renal transplantation with the cytokinesis block assay. For MN evaluation, the criteria of the Human Micron Nucleus (HUMN) project were used.
Results:
Age and sex had no influence on the number of MN before transplantation. Patients with a shorter time on dialysis had fewer MN than patients with a longer time on dialysis. After 3 weeks of immunosuppressive therapy, the ability of cells to proliferate was reduced; therefore, only 36 patients could be analyzed. In these patients, MN frequency rose significantly. There was no linear relationship between MN after transplantation and age, sex, time on dialysis or graft function. The majority of patients (79%) were treated with cyclosporine A, mycophenolate mofetil and methylprednisolone when leaving the hospital. There was no difference between the different therapeutic schemes with regard to MN frequency after transplantation, but patients with mycophenolate mofetil showed less cellular proliferation. The function of the transplanted organ or the occurrence of rejection had no effect on MN frequency after transplantation.
Conclusion:
In patients with renal transplantation, immunosuppressive therapy intensifies the genotoxic damage of the preceding chronic renal failure.
Insights
Immunosuppressive therapy after kidney transplant increases DNA damage, indicated by higher micronuclei (MN) frequency. This genotoxic effect worsens damage from prior chronic kidney disease.
Area of Science:
- Nephrology
- Genetics
- Immunology
Background:
- Immunosuppressive therapy is crucial post-renal transplant but carries mutagenic risks.
- Micronuclei (MN) frequency, assessed via cytokinesis-block assay, is a validated biomarker for DNA damage.
Purpose of the Study:
- To evaluate DNA damage, measured by MN frequency, in renal transplant recipients before and after immunosuppressive therapy.
- To correlate MN frequency with clinical factors like time on dialysis, graft function, and immunosuppressive drug regimens.
Main Methods:
- A cytokinesis-block assay was used to analyze MN frequency in 79 patients pre- and post-renal transplantation.
- Human Micron Nucleus (HUMN) project criteria were applied for MN evaluation.
Main Results:
- Pre-transplant MN frequency was not influenced by age or sex but was lower in patients with shorter dialysis times.
- Post-transplant, MN frequency significantly increased after 3 weeks of immunosuppressive therapy, with reduced cellular proliferation.
- No linear correlation was found between post-transplant MN and age, sex, dialysis duration, or graft function. Different immunosuppressive regimens did not significantly alter MN frequency, though mycophenolate mofetil was associated with less proliferation.
Conclusions:
- Immunosuppressive therapy exacerbates genotoxic damage in renal transplant patients.
- The DNA damage is intensified by immunosuppression on top of existing damage from chronic renal failure.
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