Comparing nephrotoxicity of the calcineurin inhibitors, cyclosporine A and tacrolimus, identifies their differential effects within the renal compartments, rat model

Chronic calcineurin inhibitor (CNI) nephrotoxicity is a major drawback in current immunosuppressive regimens. In the chronic setting, arteriolar hyalinosis, decreased glomerular filtration rate, interstitial fibrosis and tubular dedifferentiation are the major adverse side effects. Regimens with cyclosporine A (CsA) and tacrolimus (Tac) have been compared before the background of potentially more harmful effects of CsA. Conversely, CsA is still widely used in transplant recipients and has been considered for replacement of Tac in posttransplant diabetes.To identify regulatory mechanisms in CsA and Tac nephrotoxicity in rat, we used quantitative transcriptomics慢性钙调磷酸酶抑制剂（calcineurin inhibitor, CNI）肾毒性是当前免疫抑制治疗方案的主要弊端。在慢性病程中，小动脉玻璃样变、肾小球滤过率下降、间质纤维化与肾小管去分化是其主要不良副作用。此前已有研究以环孢素A潜在危害更强为背景，对比了环孢素A（cyclosporine A, CsA）与他克莫司（tacrolimus, Tac）的治疗方案。与之相反，环孢素A目前仍广泛应用于移植受者中，且曾被考虑用于替代他克莫司以治疗移植后糖尿病。为明确大鼠体内环孢素A与他克莫司肾毒性的调控机制，我们采用了定量转录组学技术。