Lundberg Sigrid, Westergren Emelie, Smolander Jessica, Bruchfeld Annette
Department of Nephrology, Karolinska University Hospital and Division of Renal Medicine, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-17176 Stockholm, Sweden.
Clin Kidney J. 2017 Feb;10(1):20-26. doi: 10.1093/ckj/sfw106. Epub 2016 Dec 13.
Approximately 30% of adult patients with immunoglobulin A (IgA) nephropathy (IgAN) or IgA vasculitis with nephritis (IgAVN) develop end-stage renal disease during long-term follow-up. In particular, patients with nephritic-nephrotic syndrome have an increased risk of rapid progression. Conventional immunosuppressive therapy with corticosteroids (CSs) may be insufficient for disease control and is associated with a number of side effects. Rituximab (RTX) has been shown to be well tolerated and effective in a range of glomerular diseases, but there is little information on its therapeutic potential in IgAN. The humanized anti-CD20 monoclonal antibody ofatumumab (OFAB) may be an alternative drug for patients intolerant or unresponsive to RTX, but so far there is no report on its use in IgAVN or IgAN.
We describe clinical outcomes after 17-22 months in four adult patients with biopsy-confirmed IgAVN or IgAN treated with RTX or OFAB as well as CS soon after diagnosis. All presented with nephritic-nephrotic syndrome and one had crescentic IgAN. Rebiopsy was performed in two cases.
RTX and OFAB were well tolerated. Albuminuria was <250 mg/day in three patients at last evaluation and two regained normal renal function. In all cases, renal function improved after therapy. In one patient with severe IgA vasculitis, rebiopsy showed disappearance of subendothelial but not mesangial immune complexes. In the case with crescentic IgAN, rebiopsy after 9 months showed no active necrotic lesions.
B cell-depleting therapy may be an alternative treatment for patients with IgAN or IgAVN and nephritic-nephrotic syndrome. A possible CS-sparing effect should be further evaluated in randomized controlled clinical trials.
在长期随访中，约30%的免疫球蛋白A（IgA）肾病（IgAN）或IgA血管炎伴肾炎（IgAVN）成年患者会发展为终末期肾病。特别是，患有肾炎-肾病综合征的患者快速进展的风险增加。传统的糖皮质激素（CSs）免疫抑制治疗可能不足以控制疾病，且会带来一系列副作用。利妥昔单抗（RTX）已被证明在一系列肾小球疾病中耐受性良好且有效，但关于其在IgAN中的治疗潜力的信息很少。奥法妥木单抗（OFAB）这种人源化抗CD20单克隆抗体可能是对RTX不耐受或无反应患者的替代药物，但迄今为止尚无关于其在IgAVN或IgAN中应用的报道。
我们描述了4例经活检确诊为IgAVN或IgAN的成年患者在诊断后不久接受RTX或OFAB以及CS治疗17 - 22个月后的临床结果。所有患者均表现为肾炎-肾病综合征，其中1例为新月体性IgAN。2例患者进行了重复肾活检。
RTX和OFAB耐受性良好。在最后一次评估时，3例患者的蛋白尿<250 mg/天，2例恢复了正常肾功能。在所有病例中，治疗后肾功能均有改善。1例重症IgA血管炎患者，重复肾活检显示内皮下免疫复合物消失，但系膜免疫复合物未消失。在新月体性IgAN病例中，9个月后的重复肾活检显示无活动性坏死病变。
B细胞清除疗法可能是IgAN或IgAVN及肾炎-肾病综合征患者的一种替代治疗方法。其可能的糖皮质激素节省效应应在随机对照临床试验中进一步评估。
