钙调磷酸酶抑制剂致肾损伤的研究进展

Research progress on renal injury induced by calcineurin inhibitor

钙调磷酸酶抑制剂(CNI)是一类应用广泛的免疫抑制剂,临床常用的有环孢素A和他克莫司。CNI通过抑制T细胞的活化、诱导T细胞凋亡及抑制多种免疫因子的表达等方式发挥免疫抑制作用,对系统性红斑狼疮、膜性肾病等自身免疫疾病有着显著的治疗效果。同时,CNI也存在致肾损伤的毒副作用。CNI可通过激活肾素-血管紧张素-醛固酮系统、破坏肾脏局部血管活性物质的平衡、促进氧化应激等多种方式对肾小球、肾小血管和肾小管及肾间质产生不同程度的损伤。尿视黄醇结合蛋白等生物标志物可能对早期检测CNI所致的肾损伤具有一定价值。钙离子通道拮抗剂则被认为是减轻CNI所致肾损伤的有效手段。本文旨在为应对CNI所致肾损伤提供理论依据和防治思路,促进临床中合理、安全地使用CNI。

Calcineurin inhibitor(CNI)is a kind of widely used immunosuppressive drug.Ciclosporin A and Tacrolimus are commonly used in clinic.CNI exerts immunosuppressive effects by inhibiting T cell activation,inducing T cell apoptosis,and inhibiting the expression of various immune factors,and has significant therapeutic effects on autoimmune diseases such as systemic lupus erythematosus and membranous nephropathy.Meanwhile,CNI also has toxic side effects that can cause kidney damage.CNI can damage the glomerulus,renal microvasculature,renal tubules,and renal interstitium to varying degrees by activating the renin-angiotension-aldosterone system,destroying the balance of local vasoactive substances in the kidney,promoting oxidative stress,and other ways.Urinary retinol binding protein and other biomarkers may have some value in early detection of renal injury caused by CNI.Calcium channel blocker is considered as an effective means to alleviate CNI induced renal injury.This article aims to provide theoretical basis and prevention and treatment ideas for renal injury caused by CNI,and promote the rational and safe use of CNI in clinical practice.