Mutagenicity of immunosuppressive medications among renal transplant recipients.
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.


CONCLUSIONS
In patients with renal transplantation, immunosuppressive therapy intensifies the genotoxic damage of the preceding chronic renal failure.
Rath
Thomas
T
Department of Nephrology and Transplantation Medicine, Medical Clinics III, Westpfalz-Klinikum, Kaiserslautern, Germany. trath@westpfalz-klinikum.de
Oliveira-Frick
Vilma
V
D000328:Adult; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007676:Kidney Failure, Chronic / Q000235:genetics / Q000276:immunology / Q000601:surgery; D016030:Kidney Transplantation; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D008875:Middle Aged; D009153:Mutagens / Q000008:administration & dosage / Q000009:adverse effects*; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects
D007166:Immunosuppressive Agents; D009153:Mutagens; D013256:Steroids; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D008775:Methylprednisolone