Kabat-Koperska Joanna, Kolasa-Wołosiuk Agnieszka, Baranowska-Bosiacka Irena, Safranow Krzysztof, Kosik-Bogacka Danuta, Gutowska Izabela, Pilutin Anna, Gołembiewska Edyta, Kędzierska Karolina, Ciechanowski Kazimierz
Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
Department of Histology and Embryology, Pomeranian Medical University, Powstancow Wielkopolskich 72, 70-111, Szczecin, Poland.
Apoptosis. 2016 Nov;21(11):1240-1248. doi: 10.1007/s10495-016-1281-y.
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.
怀孕会给肾脏带来显著的额外负担。我们研究的目的是调查免疫抑制药物对怀孕期接触过这些药物的雌性Wistar大鼠天然肾脏变化的影响。该研究对32只母鼠进行，它们接受了常用于人类肾移植受者治疗的免疫抑制方案（环孢素A、霉酚酸酯和泼尼松；他克莫司、霉酚酸酯和泼尼松；环孢素A、依维莫司和泼尼松）。这些动物在怀孕前2周和怀孕3周期间接受药物治疗。在所有接受治疗的母鼠中，发现体重下降（但肾脏质量未下降）以及血清钠和氯离子发生变化；用环孢素A、依维莫司和泼尼松治疗的母鼠血清肌酐浓度升高。所有治疗组的母鼠远端小管凋亡均增加。组织学检查发现，用钙调神经磷酸酶抑制剂、霉酚酸酯和泼尼松治疗的大鼠肾脏中，上皮细胞嗜酸性或嗜碱性细胞质的强度发生了变化。所有免疫抑制方案均导致影响肾单位小管的异常。含有钙调神经磷酸酶抑制剂和霉酚酸酯的方案导致更高的凋亡率和更明显的组织病理学变化。基于依维莫司的方案尽管近端小管凋亡率较低且肾脏损伤标志物积累较少，但血清肌酐浓度较高。因此，对于怀孕雌性大鼠肾脏长期功能而言，哪种药物组合更好或更差，还需要进一步研究。
