Journal of Clinical & Experimental Pharmacology

Abstract

Influence of Intrauterine Exposure to Safe and Contraindicated Immunosuppressive Drugs In Combinations during Pregnancy on Morphology and Function of Kidneys in Juvenile Wistar Rats

Joanna Kabat-Koperska*,Agnieszka Kolasa-Wolosiuk,Irena Baranowska-Bosiacka,Krzysztof Safranow,Danuta Kosik-Bogacka,Izabela Gutowska,Anna Pilutin,Edyta Golembiewska,Karolina Kedzierska,Leszek Domanski,Kazimierz Ciechanowski

Abstract Objective: In the study we focused on the impact of ?safe? and ?contraindicated? immunosuppressive drugs in combinations during pregnancy on changes in native kidneys in juvenile Wistar rats after exposure of pregnant female rats to these drugs. Method: The study was conducted on 32 female (full dose of drugs) and 8 female Wistar rats (half dose of drugs), subjected to immunosuppressive regimens commonly used in therapy of human kidney transplant recipients. The animals received drugs by oral gavage 2 weeks before pregnancy and during 3 weeks of pregnancy. Results: Basing on serum creatinine concentrations, combination of tacrolimus, mycophenolate mofetil and prednisone turned out to be less harmful to the kidney than combination of cyclosporine A, mycophenolate mofetil and prednisone or cyclosporine A, everolimus and prednisone. Neutrophil-gelatinase associated lipocalin (NGAL) concentration in kidney seemed to be dose-dependent in rats treated with cyclosporine A, mycophenolate mofetil and prednisone. Morphological changes in kidneys in juvenile rats exposed to immunosuppressive treatment in utero were more pronounced in the first 3 weeks of life and diminished with age. In rats exposed to cyclosporine A, everolimus and prednisone we have observed a decrease in thickness of renal cortex and reduced diameter of glomeruli. These changes were still evident in 8-week-old animals. Conclusion: Combination of tacrolimus, mycophenolate mofetil and prednisone turned out to be the least harmful to the kidney (the lowest creatinine concentrations); combination of cyclosporine A, everolimus and prednisone appeared to be the most harmful one ? we observed not only an increase in serum creatinine concentrations but a decrease in thickness of renal cortex and reduced diameter of glomeruli as well.