IgA 肾病的新视野:聚焦当前治疗和新兴解决方案

Eleanor Roberts
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摘要

IgA 肾病(IgAN)是一种常见的肾小球疾病,其症状发生和发展具有广泛的异质性。诊断依据是肾活检结果。IgAN 起病于粘膜,会产生半乳糖缺乏性 IgA1(Gd-IgA1)和抗 Gd-IgA1 自身抗体,导致这些复合物沉积在肾小球系膜中,造成纤维化、炎症、肾小管间质瘢痕和肾小球损伤。这可能导致慢性肾病(CKD)、肾衰竭和死亡。IgAN 的治疗包括优化支持性护理,包括针对症状的个体化策略,如控制高血压和心血管风险。药物治疗包括肾素-血管紧张素-醛固酮系统(RAAS)抑制剂和免疫抑制剂疗法。虽然后者可以成功降低蛋白尿,并对估计肾小球滤过率(eGFR)产生积极影响,但不良反应会限制治疗持续时间,而且在停止治疗后,蛋白尿增加和 eGFR 下降的情况可能会再次出现。免疫抑制剂疗法的新配方包括在产生 Gd-IgA1 的小肠下部定向释放的缓释布地奈德。虽然与其他免疫抑制剂疗法类似,使用这种药物治疗可以减少蛋白尿并维持 eGFR 水平,但效果似乎主要局限于积极治疗期间。针对不同的机制,sparsentan 是一种双重内皮素 A 受体(ETA)和血管紧张素 II 受体 1 型(AT1)阻断剂,其作用靶点是内皮素-1(ET-1)和血管紧张素 II,两者都参与了 IgAN 的进展。初步的 III 期试验结果显示,与 AT1 受体阻滞剂厄贝沙坦相比,斯帕生坦在蛋白尿方面有显著差异,但不良反应情况相似。这些药物和其他几种在研药物将拓宽IgAN患者的治疗手段,联合使用时可针对IgAN发病机制的不同方面,采取更加个体化的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
New Horizons in IgA Nephropathy: A Focus on Current Treatment and Emerging Solutions
IgA nephropathy (IgAN) is a common form of glomerular disease, with wide heterogeneity of symptom occurrence and progression. Diagnosis is based on kidney biopsy findings. IgAN initiates in the mucosa with development of galactose-deficient IgA1 (Gd-IgA1) and anti-Gd-IgA1 autoantibodies, leading to deposition of these complexes in glomerular mesangium with resulting fibrosis, inflammation, tubulointerstitial scarring, and glomerular injury. This can lead to chronic kidney disease (CKD), kidney failure, and death. IgAN treatment involves optimised supportive care, including individualised strategies to address symptoms, such as high blood pressure control and cardiovascular risks. Drug treatment includes renin-angiotensin-aldosterone system (RAAS) inhibitors and immunosuppressant therapies. While the latter can successfully lower proteinuria, and have a positive effect on estimated glomerular filtration rate (eGFR), adverse effects can limit treatment duration, and increasing proteinuria and decreasing eGFR can return following treatment discontinuation. New formulations of immunosuppressant therapies include delayed-release budesonide with targeted release in the lower part of the small intestine where Gd-IgA1 production occurs. Although treatment with this drug can reduce proteinuria and sustain eGFR levels, similar to other immunosuppressant therapies, effects seem to be predominantly limited to the active treatment period. Targeting a different mechanism, sparsentan is a dual endothelin A receptor (ETA) and angiotensin II receptor type 1 (AT1) blocker that targets endothelin-1 (ET-1) and angiotensin II, both involved in IgAN progression. Initial Phase III trial results show significant differences, favouring sparsentan, compared with the AT1 blocker irbesartan, on proteinuria, with similar adverse event profiles. These agents, and several other drugs in development, will widen the armamentarium of therapies for people with IgAN, which, when used in combination, can target different aspects of IgAN pathogenesis for a more individualised treatment approach.
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