Department of Nephrology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India, 576104.
J Nephrol. 2023 Nov;36(8):2191-2208. doi: 10.1007/s40620-023-01733-6. Epub 2023 Aug 2.
Hydroxychloroquine is one of the oldest disease-modifying anti-rheumatic drugs in clinical use. The drug interferes with lysosomal activity and antigen presentation, inhibits autophagy, and decreases transcription of pro-inflammatory cytokines. Owing to its immunomodulatory, anti-inflammatory, anti-thrombotic effect, hydroxychloroquine has been an integral part of therapy for systemic lupus erythematosus and lupus nephritis for several decades. The therapeutic versatility of hydroxychloroquine has led to repurposing it for other clinical conditions, with recent studies showing reduction in proteinuria in IgA nephropathy. Research is also underway to investigate the efficacy of hydroxychloroquine in primary membranous nephropathy, Alport's syndrome, systemic vasculitis, anti-GBM disease, acute kidney injury and for cardiovascular risk reduction in chronic kidney disease. Hydroxychloroquine is well-tolerated, inexpensive, and widely available and therefore, should its indications expand in the future, it would certainly be welcomed. However, clinicians should be aware of the risk of irreversible and progressive retinal toxicity and rarely, cardiomyopathy. Monitoring hydroxychloroquine levels in blood appears to be a promising tool to evaluate compliance, individualize the dose and reduce the risk of retinal toxicity, although this is not yet standard clinical practice. In this review, we discuss the existing knowledge regarding the mechanism of action of hydroxychloroquine, its utility in lupus nephritis and other kidney diseases, the main adverse effects and the evidence gaps that need to be addressed in future research. Created with Biorender.com. HCQ, hydroxychloroquine; GBM, glomerular basement membrane; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; TLR, toll-like receptor.
羟氯喹是临床应用中最古老的疾病修饰抗风湿药物之一。该药物干扰溶酶体活性和抗原呈递，抑制自噬，并降低促炎细胞因子的转录。由于其免疫调节、抗炎、抗血栓作用，羟氯喹几十年来一直是系统性红斑狼疮和狼疮性肾炎治疗的重要组成部分。羟氯喹的治疗多功能性导致其被重新用于其他临床情况，最近的研究表明其可减少 IgA 肾病的蛋白尿。目前还在研究羟氯喹在原发性膜性肾病、Alport 综合征、系统性血管炎、抗肾小球基底膜疾病、急性肾损伤和慢性肾脏病心血管风险降低中的疗效。羟氯喹耐受性好、价格低廉且广泛可用，因此，如果其适应证在未来扩大，肯定会受到欢迎。然而，临床医生应该意识到不可逆和进行性视网膜毒性以及罕见的心肌病的风险。监测血液中的羟氯喹水平似乎是一种评估依从性、个体化剂量和降低视网膜毒性风险的有前途的工具，尽管这尚未成为临床常规实践。在这篇综述中，我们讨论了关于羟氯喹作用机制、在狼疮性肾炎和其他肾脏疾病中的应用、主要不良反应以及未来研究中需要解决的证据空白的现有知识。
