Combination therapy of cyclosporine A and mycophenolate mofetil in rats with adriamycin-induced nephrotic syndrome

Aim: The lack of effective treatment for steroid-resistant nephrotic syndrome has led to the search for new treatments and the emergence of combined thera-pies. In our study, we aimed to reduce side effects and increase effectiveness by combination with low-dose cyclosporine and MMF. Material and Methods: Fifty Wistar albino rats were included in our study. Five groups were formed as follows: untreated nephrotic syndrome, cyclosporine, MMF, low-dose cyclosporine, and a combined therapy group. Nephrotic syndrome parameters were studied. Rats were sacrificed at the end of the study. Glo-merulosclerotic index, interstitial fibrosis score, and total damage score were calculated with histopathological examination. Results: Urine protein/creatinine significantly decreased in the MMF and low-dose CsA groups after treatment. Serum total protein and albumin levels were preserved better in the combined therapy group. The control of hyperlipidemia was better in the combined therapy group than the others. The best results for oxidative damage were detected in the low-dose CsA and combined therapy groups. Serum creatine was detected to be higher in the CsA group than in other groups. The glomerulosclerotic index and total damage score were found to be significantly higher in the CsA group compared to other groups. The interstitial fibrosis score was found to be significantly higher in the MMF group compared to the combined therapy group. TGF-beta was significantly higher in the MMF group compared to the CsA group. Osteopontin was significantly lower in the CsA group than the other groups. Discussion: This study showed that while MMF and low dose CsA have similar successful effects in protecting serum protein and creatinine, oxidative stress can be kept lower by using low-dose CsA, and hyperlipidemia can be suppressed more successfully with combined therapy.