The effect of immunosuppressive therapy on renal cell apoptosis in native rat kidneys
Karolina Kędzierska1, Katarzyna Sporniak-Tutak2, Agnieszka Kolasa3, Leszek Domański1, Maciej Domański1, Krzysztof Sindrewicz2, Tomasz Smektała2, Joanna Bober4, Krzysztof Safranow5, Bogumiła Osękowska1, Joanna Kabat-Koperska1, Irena
Baranowska-Bosiacka5, Mirosław Parafiniuk6, Elżbieta Urasińska7 and Kazimierz Ciechanowski1
1Department of Nephrology, Transplantology and Internal Medicine, 2Department of Dental Surgery, 3Department of Histology and Embryology, 4Department of Medical Chemistry, 5Department of Biochemistry, 6Department of Forensic Medicine and 7Department of Pathomorphology Pomeranian Medical University, Szczecin, Poland
Offprint requests to: Karolina Kędzierska, Department of Nephrology, Transplantology and Internal Medicine, Powstańców Wlkp. 72, 70-111 Szczecin, Pomeranian Medical University, Szczecin, Poland. e-mail: karolina.kedzierska@interia.pl
Summary. Aim: To analyse the impact of the most commonly used immunosuppressive drugs on the occurrence of apoptosis in the native kidneys of Wistar rats. Method: The study involved 36 rats. The animals grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporine A, rapamycin and prednisone). The rats in all study groups were treated with a 3-drug protocol for 6 months. The medication dose was adjusted based on available literature data. No drugs were administered to the control group. The rats were then killed. Autopsies of all animals were performed and the kidneys were isolated for histopathology (HE + PAS). To assess cell apoptosis the TUNEL reaction was performed. Blood trough levels of immunosuppressive drugs as well as the parameters of peripheral blood were determined. Results: 1. In rats treated with cyclosporine A distal nephron tubules were characterised by more pronounced apoptosis. 2. In tacrolimus-treated rats a lower intensity of apoptosis was found in the distal tubules. 3. In rapamycin-treated rats the apoptosis was inhibited both in the distal and proximal nephron tubules. 4. In MMF treated rats intense apoptosis was observed in the proximal nephron tubules. 5. There were no significant changes in renal histopathology (HE + PAS). Conclusions: The apoptosis in nephron tubules caused by immunosuppressive therapy is not accompanied by any histopathological changes (eg fibrosis, inflammation, tubular atrophy, vacuolation of the tubular cells) in light microscopy. Histol Histopathol 30, 105-116 (2015)
Key words: Apoptosis, Immunosuppression, Drug effects, Transplantation, Kidney
DOI: 10.14670/HH-30.105