The long-term effects of rapamycin-based immunosuppressive protocols on the expression of renal aquaporins 1, 2, 3 and 4 water channels in rats

Abstract

Background. To this day, the effect of multidrug immunosuppressive protocols on renal expression of AQPs is unknown. This study aimed to determine the influence of rapamycin-based multi-drug immunosuppressive regimens on the expression of aquaporins (AQPs) 1, 2, 3, and 4 in the rat kidney. Methods. For 6 months, 24 male Wistar rats were administered immunosuppressants, according to the three-drug protocols used in patients after organ transplantation. The rats were divided into four groups: the control group, the TRP group (tacrolimus, rapamycin, prednisone), the CRP group (cyclosporine A, rapamycin, prednisone), and the MRP group (mycophenolate mofetil, rapamycin, prednisone). Selected red cell indices and total calcium were measured in the blood of rats and quantitative analysis of AQP1, AQP2, AQP3 and AQP4 immunoexpression in the kidneys were performed. Results. In the TRP and CRP groups, a mild increase of mean corpuscular hemoglobin concentration, hematocrit and total calcium were observed. Moreover, decreased expression of AQP1-4 was found in all experimental groups, with the highest decrease in the CRP group. Conclusions. The long-term immunosuppressive treatment using multi-drug protocols decreased AQP1-4 expressions in renal tubules, possibly leading to impaired urine-concentrating ability in rat