Cyclosporine A (CsA) is a widely used immunosuppressive agent that greatly reduces the rates of kidney-, heart-, and liver-transplant rejection. However, CsA nephrotoxicity is a serious side effect that limits the clinical use of CsA. While the mechanisms underlying CsA nephrotoxicity are still not fully understood, increasing lines of evidence suggest that oxidative stress plays an important role in this phenomenon. Specifically, CsA induces endoplasmic reticulum stress and increases mitochondrial reactive oxygen species production: this modifies the redox balance, which causes lipid peroxidation and thereby induces nephrotoxicity. Recent studies on the pathogenesis of CsA nephrotoxicity suggest that CsA-induced autophagy can alleviate the deleterious effects of CsA-induced endoplasmic reticulum stress, thereby preventing nephrotoxicant-induced renal injury. A variety of signaling pathways participate in the pathogenesis of CsA nephrotoxicity. Specifically, the p38, ERK, and JNK MAPK subfamilies are all involved in CsA nephrotoxicity, while NF-κB is a target molecule of CsA. Moreover, the fibrogenic cytokine TGF-β1 contributes to CsA-induced renal fibrosis, while Nrf2 modulates CsA-induced cellular oxidative stress. In addition, CsA generally inhibits nitric oxide synthesis and impairs endothelium-dependent relaxation in the renal artery. However, some reports also suggest that nitric oxide synthesis is enhanced in the kidney cortex during CsA nephrotoxicity. Notably, the biomarkers of CsA nephrotoxicity associated with CsA have not been reviewed previously. Therefore, in this review, we will first provide an update on CsA nephrotoxicity in humans and describe the potential biomarkers of CsA nephrotoxicity. The molecular and cellular mechanisms that underlie CsA nephrotoxicity and the roles played by oxidative stress, autophagy, and signaling pathways will then be comprehensively summarized and discussed. Finally, the current therapeutical strategies for CsA nephrotoxcixity are summarized. We hope this review will provide a better understanding of CsA nephrotoxicity, thereby improving the management of patients who are treated with CsA.

环孢霉素A（CsA）是一种广泛使用的免疫抑制剂，可大大降低肾脏，心脏和肝脏移植排斥的发生率。但是，CsA的肾毒性是严重的副作用，限制了CsA的临床使用。虽然尚不完全了解CsA肾毒性的潜在机制，但越来越多的证据表明氧化应激在该现象中起重要作用。具体而言，CsA诱导内质网应激并增加线粒体活性氧的产生：这会改变氧化还原平衡，从而引起脂质过氧化，从而引起肾毒性。CsA肾毒性发病机理的最新研究表明，CsA诱导的自噬可以减轻CsA诱导的内质网应激的有害影响，从而预防肾毒性药物引起的肾损伤。多种信号通路参与CsA肾毒性的发病机制。具体而言，p38，ERK和JNK MAPK亚家族均参与CsA的肾毒性，而NF-κB是CsA的靶分子。此外，成纤维细胞因子TGF-β1促进了CsA诱导的肾纤维化，而Nrf2调节了CsA诱导的细胞氧化应激。此外，CsA通常会抑制一氧化氮的合成，并损害肾动脉的内皮依赖性舒张功能。但是，一些报告还表明，在CsA肾毒性期间，肾脏皮质中一氧化氮的合成会增强。值得注意的是，与CsA相关的CsA肾毒性的生物标志物以前没有被审查过。因此，在这篇评论中，我们将首先提供有关人类CsA肾毒性的最新信息，并描述CsA肾毒性的潜在生物标志物。然后将对CsA肾毒性的分子和细胞机制以及氧化应激，自噬和信号传导途径所起的作用进行全面总结和讨论。最后，总结了目前CsA肾毒性的治疗策略。我们希望这篇综述可以更好地了解CsA的肾毒性，从而改善用CsA治疗的患者的管理。总结了目前CsA肾毒性的治疗策略。我们希望这篇综述可以更好地了解CsA的肾毒性，从而改善用CsA治疗的患者的管理。总结了目前CsA肾毒性的治疗策略。我们希望这篇综述可以更好地了解CsA的肾毒性，从而改善用CsA治疗的患者的管理。