Dantal J, Bigot E, Bogers W, Testa A, Kriaa F, Jacques Y, Hurault de Ligny B, Niaudet P, Charpentier B, Soulillou J P
Service de Néphrologie-Immunologie Clinique, Centre hospitalier régional et universitaire, Nantes, France.
N Engl J Med. 1994 Jan 6;330(1):7-14. doi: 10.1056/NEJM199401063300102.
Among patients with the idiopathic nephrotic syndrome who have focal and segmental glomerulosclerosis and undergo renal transplantation, 15 to 55 percent have recurrent nephrotic syndrome. The recurrence may be caused by a plasma factor or factors that increase glomerular permeability, because plasma exchange transiently decreases or abolishes proteinuria in some patients. We studied the effect on proteinuria of the removal of protein (mostly immunoglobulins) by adsorption onto protein A from the plasma of patients with recurrent nephrotic syndrome.
Eight patients were treated with one to three cycles of two to seven 1-day sessions of protein adsorption, and the patients' urinary protein excretion was measured repeatedly. Their immunosuppressive regimens were not changed during the treatment. The adsorbed proteins were eluted from the protein A and injected into rats, and the urinary albumin excretion of the rats was measured.
The protein-adsorption treatment consistently decreased urinary protein excretion by an average of 82 percent at the end of a cycle (P < 0.001). In one patient proteinuria disappeared, and in another urinary protein excretion remained below 2.5 g per day with repeated cycles of protein adsorption. In all but one patient the effect of adsorption was limited in time, with a return to the preadsorption level of protein excretion within a maximum of two months. The administration to rats of material eluted from the protein A increased urinary albumin excretion 2.9- to 4.6-fold (P < 0.001 and P = 0.005, respectively). Although protein A primarily binds immunoglobulins, the active fraction of the eluted proteins had a molecular weight below 100,000, indicating that immunoglobulin was not directly involved.
Adsorption of plasma protein decreases urinary protein excretion in patients with recurrence of the nephrotic syndrome after renal transplantation. Studies of the adsorbed proteins should provide information about the mechanism of this disease.
在患有局灶节段性肾小球硬化并接受肾移植的特发性肾病综合征患者中,15%至55%会出现肾病综合征复发。复发可能由一种或多种增加肾小球通透性的血浆因子引起,因为血浆置换可使部分患者的蛋白尿暂时减少或消失。我们研究了通过蛋白A吸附去除复发肾病综合征患者血浆中的蛋白质(主要是免疫球蛋白)对蛋白尿的影响。
8例患者接受了1至3个疗程、每次2至7个为期1天的蛋白吸附治疗,并反复测量患者的尿蛋白排泄量。治疗期间其免疫抑制方案不变。将吸附的蛋白质从蛋白A上洗脱下来并注射到大鼠体内,测量大鼠的尿白蛋白排泄量。
蛋白吸附治疗在一个疗程结束时持续使尿蛋白排泄量平均降低82%(P<0.001)。1例患者蛋白尿消失,另一例患者经反复的蛋白吸附疗程后尿蛋白排泄量维持在每天2.5 g以下。除1例患者外,其他所有患者的吸附效果在时间上都有限,最多在两个月内尿蛋白排泄量就恢复到吸附前水平。给大鼠注射从蛋白A上洗脱下来的物质后,尿白蛋白排泄量增加了2.9至4.6倍(分别为P<0.001和P = 0.005)。虽然蛋白A主要结合免疫球蛋白,但洗脱蛋白的活性部分分子量低于100,000,表明免疫球蛋白并非直接参与其中。
肾移植后肾病综合征复发患者的血浆蛋白吸附可降低尿蛋白排泄量。对吸附蛋白的研究应能提供有关该疾病机制的信息。