PDF(Pubmed)
Abstract：
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. It is characterized by the mesangial deposition of IgA-containing immune complexes, triggering damage to the glomerular filtration barrier that is amplified by the tandem action of endothelin-1 and angiotensin II at their receptors. Proteinuria and progressive glomerular damage cause loss of kidney function in up to 50% of patients within 10-20 years. The risk of progression is strongly associated with persistent proteinuria (>0.75-1 g/day). Current standard of care involves interventions to decrease proteinuria and control blood pressure. Immunosuppressive agents, used in selected patients at high risk for progression, can be associated with significant side effects. Sparsentan, a novel non-immunosuppressive single-molecule Dual Endothelin Angiotensin Receptor Antagonist (DEARA), received FDA accelerated approval based on interim results from the PROTECT trial, which demonstrated that sparsentan-treated patients achieved a significantly greater reduction in proteinuria from baseline versus the active control irbesartan and that sparsentan was generally safe and well tolerated. Sparsentan is the first non-immunosuppressive treatment to be FDA-approved for the reduction of proteinuria in adults with IgAN at high risk of disease progression. We provide practical guidance for the clinical use of sparsentan in adults with IgAN.
摘要：
免疫球蛋白A肾病(IgAN)是全球最常见的原发性肾小球肾炎。它的特征是含有IgA的免疫复合物的系膜沉积，通过内皮素-1和血管紧张素II在其受体上的串联作用，可触发对肾小球滤过屏障的损害。蛋白尿和进行性肾小球损伤导致高达50％的患者在10-20年内失去肾功能。进展风险与持续性蛋白尿（>0.75-1g/天）密切相关。目前的护理标准包括减少蛋白尿和控制血压的干预措施。免疫抑制剂，用于某些进展风险高的患者，可能与显著的副作用有关。Sparsentan,一种新型非免疫抑制性单分子双内皮素血管紧张素受体拮抗剂(DEARA),根据PROTECT试验的中期结果获得了FDA的加速批准，这表明,与主动对照厄贝沙坦相比,接受斯帕生坦治疗的患者的蛋白尿比基线显著减少,并且斯帕生坦总体上是安全且耐受性良好的.Sparsentan是FDA批准的第一种非免疫抑制治疗方法，用于减少患有疾病进展高风险的IgAN成人的蛋白尿。我们为Sparsentan在成人IgAN中的临床使用提供了实用指导。
