Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY; Recanati-Miller Transplant Institute, Mount Sinai Hospital, New York, NY.
Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
Adv Chronic Kidney Dis. 2020 Jan;27(1):56-66. doi: 10.1053/j.ackd.2019.08.006.
Calcineurin inhibitors (CNIs) are both the savior and Achilles' heel of kidney transplantation. Although CNIs have significantly reduced rates of acute rejection, their numerous toxicities can plague kidney transplant recipients. By 10 years, virtually all allografts will have evidence of CNI nephrotoxicity. CNIs have been strongly associated with hypertension, dyslipidemia, and new onset of diabetes after transplantation-significantly contributing to cardiovascular risk in the kidney transplant recipient. Multiple electrolyte derangements including hyperkalemia, hypomagnesemia, hypercalciuria, metabolic acidosis, and hyperuricemia may be challenging to manage for the clinician. Finally, CNI-associated tremor, gingival hyperplasia, and defects in hair growth can have a significant impact on the transplant recipient's quality of life. In this review, the authors briefly discuss the pharmacokinetics of CNI and discuss the numerous clinically relevant toxicities of commonly used CNIs, cyclosporine and tacrolimus.
钙调磷酸酶抑制剂（CNI）是肾移植的救星和阿喀琉斯之踵。尽管 CNI 显著降低了急性排斥反应的发生率，但它们的许多毒性也会困扰肾移植受者。10 年后，几乎所有的同种异体移植物都会出现 CNI 肾毒性的证据。CNI 与高血压、血脂异常和移植后新发糖尿病密切相关，这显著增加了肾移植受者的心血管风险。多种电解质紊乱，包括高钾血症、低镁血症、高钙尿症、代谢性酸中毒和高尿酸血症，可能对临床医生的管理构成挑战。最后，CNI 相关的震颤、牙龈增生和毛发生长缺陷会对移植受者的生活质量产生重大影响。在这篇综述中，作者简要讨论了 CNI 的药代动力学，并讨论了常用 CNI（环孢素和他克莫司）的许多临床相关毒性。
