title: The influence of exposure to immunosuppressive treatment during pregnancy on renal function and rate of apoptosis in native kidneys of female Wistar rats.
abstract: Pregnancy puts a significant additional strain on kidneys. The aim of our study was to investigate the impact of immunosuppressive drugs on changes in native kidneys in female Wistar rats after exposure during pregnancy. The study was conducted on 32 dams, subjected to immunosuppressive regimens commonly used in the therapy of human kidney transplant recipients (cyclosporine A, mycophenolate mofetil and prednisone; tacrolimus, mycophenolate mofetil and prednisone; cyclosporine A, everolimus and prednisone). The animals received drugs for 2 weeks before pregnancy and during 3 weeks of pregnancy. In all treated dams lower body weight (but not kidney mass) and alterations in serum sodium and chloride ions were found; serum creatinine concentration was increased in dams treated with cyclosporine A, everolimus and prednisone. All treatment groups of dams showed increased apoptosis in the distal tubules. In histological examination the changed intensity of acidophilic or basophilic cytoplasm of epithelial cells was found in kidneys of rats treated with calcineurin inhibitors, mycophenolate mofetil and prednisone. All immunosuppressive regimens caused abnormalities affecting nephron tubules. Regimens containing calcineurin inhibitors and mycophenolate mofetil caused higher rate of apoptosis and more pronounced histopathological changes. Regimen based on everolimus despite the lower rate of apoptosis in the proximal tubules and lower accumulation of kidney injury markers revealed higher serum creatinine concentration. Thus, interpretation which combination of drugs is better or worse for long-lasting functioning of kidneys in pregnant females requires further studies.
authors: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland. askodom@poczta.onet.pl.
authors: Joanna
authors: J
authors: Kabat-Koperska
authors: Department of Histology and Embryology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Agnieszka
authors: A
authors: Kolasa-Wołosiuk
authors: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Irena
authors: I
authors: Baranowska-Bosiacka
authors: Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Krzysztof
authors: K
authors: Safranow
authors: Department of Biology and Medical Parasitology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Danuta
authors: D
authors: Kosik-Bogacka
authors: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Broniewskiego 24, 71-460, Szczecin, Poland.
authors: Izabela
authors: I
authors: Gutowska
authors: Department of Histology and Embryology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Anna
authors: A
authors: Pilutin
authors: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Edyta
authors: E
authors: Gołembiewska
authors: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Karolina
authors: K
authors: Kędzierska
authors: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
authors: Kazimierz
authors: K
authors: Ciechanowski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects; D000068338:Everolimus / Q000009:adverse effects; D005260:Female; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology*; D007677:Kidney Function Tests; D009173:Mycophenolic Acid / Q000009:adverse effects; D011241:Prednisone / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D016559:Tacrolimus / Q000009:adverse effects
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000068338:Everolimus; D003404:Creatinine; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus
keywords: Immunosuppressive drugs; Kidney; Pregnancy; Transplantation; Wistar rats