肾移植受者中钙调神经磷酸酶抑制剂致疼痛综合征的临床特征及治疗

Clinical features and treatment of calcineurin inhibitor-induced pain syndrome in renal transplant recipients

目的了解肾移植受者中钙调神经磷酸酶抑制剂致疼痛综合征(calcineurin inhibitor induced pain syndrome,CIPS)的临床特征及其治疗方法。方法通过检索1991年1月至2020年12月PubMed、Google学术、中国知网、万方、维普等获得可能相关的全文或摘要,剔除综述、非肾移植受者以及重复的文献。最终纳入11篇文章,共包括15例病例报告。结果诊断CIPS时患者的平均年龄为(44.6±8.31)岁,男性患者比例为53.3%。CIPS出现的平均时间为肾移植后(2.42±3.07)个月。受累的部位主要包括双侧手、肘、腕、膝盖、脚踝、双足以及后背。实验室检查提示:发生CIPS时钙调神经磷酸酶抑制剂(calcineurin inhibitors,CNIs)的谷浓度升高或正常,部分患者的碱性磷酸酶、甲状旁腺激素、血钙、C反应蛋白水平升高,血磷水平异常,而类风湿因子、尿酸水平正常。通过减少CNIs剂量或更换CNIs种类,静脉注射帕米膦酸,加用普瑞巴林、钙通道拮抗剂等,多数患者CIPS症状消失,症状好转时间为(4.43±3.31)个月。结论 CIPS的最有效治疗方法是减少CNIs的剂量和更换免疫抑制剂,其他治疗方式包括给予GABA类似物、帕米膦酸钠、钙通道阻滞剂和保守疗法。

Objective To understand the clinical features and therapeutic methods for calcineurin inhibitor-induced pain syndrome(CIPS) in kidney transplant recipients. Methods The related articles or abstracts from January 1991 to December 2020 were obtained by searching PubMed, Google Scholar, CNKI, Wanfang and VIP databases. The reviews, duplicate literatures and the articles involved in non-kidney transplant recipients were excluded. 11 full papers were included with 15 case reports. Results The average age of patients at the time of diagnosis of CIPS was(44.6±8.31) years, and the 53.3% of the patients was male. The average appearance time of CIPS was(2.42±3.07) months after kidney transplantation. CIPS mainly affected bilateral hands, elbows, wrists,knees, ankles, feet and back. The patients had normal or elevated trough concentrations of calcineurin inhibitors(CNIs) when CIPS occurred. Some patients had elevated alkaline phosphatase, parathyroid hormone, blood calcium, C-reactive protein levels, and abnormal phosphorus levels, while rheumatoid factor and uric acid levels were normal. CIPS symptoms in most patients disappeared with dose reduction of CNIs, change to different class of CNIs, pamidronate IV injection, pregabalin, calcium channel antagonists,etc. The average recovery time was(4.43±3.31) months. Conclusion The most effective treatment for CIPS is to reduce the dose of CNIs and replace immunosuppressants. Other treatments include GABA analogs, intravenous pamidronate, calcium channel blockers and conservative therapy.