Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats

Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats
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DOI:
10.1172/jci200212858
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发表时间:
2002-02-01
影响因子:
15.9
通讯作者:
Dantal, J
Dantal, J
中科院分区:
医学1区
文献类型:
--
作者:
Le Berre, L;Godfrin, Y;Dantal, J

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布法罗/Mna大鼠自发发展局灶节段性肾小球硬化症,其组织学模式与人类疾病相似。在这项研究中,我们通过将正常肾脏移植到布法罗/MNA受体中来研究疾病复发的可能性。将来自健康LEW. 1 W大鼠的肾脏移植到蛋白尿的6个月大的布法罗/Mna大鼠中,在供体特异性输血(DST)后不进行或进行特异性耐受诱导,目的是控制宿主抗供体免疫应答。进行反向组合以确定蛋白尿布法罗/Mna肾是否可以在正常环境中恢复其选择透过性。作为对照,将LEW. 1 W肾移植到Wistar Furth受体中。在没有DST的移植后,LEW.1W肾的蛋白尿复发出现在大约10天,可能与移植物的排斥反应有关。在与DST相同的组合中,20天后出现蛋白尿,伴随的肾小球损伤表明最初的肾脏疾病复发。移植的对照动物保持无蛋白尿。在相反的组合,蛋白尿和病变的布法罗/MNA肾移植到健康的LEW. 1 W大鼠后消退。布法罗/Mna肾移植后蛋白尿复发和布法罗/Mna肾移植到正常宿主后病变缓解表明,布法罗/Mna大鼠表达循环蛋白尿因子,这可能与人类特发性肾病综合征的复发有关。
Buffalo/Mna rats spontaneously develop a focal segmental glomerulosclerosis with a histological pattern similar to the human disease. in this study, we investigated the potential of recurrence of the disease by transplantation of normal kidneys into Buffalo/Mna recipients. Kidneys from healthy LEW.1W rats were grafted into proteinuric 6-month-old Buffalo/Mna rats without or with specific tolerance induction following donor-specific transfusion (DST) aimed at controlling host anti-donor immune responses. The inverse combination was carried out to determine whether a proteinuric Buffalo/Mna kidney can recover its permselectivity in a normal environment. As a control, LEW.1W kidneys were grafted into Wistar Furth recipients. After transplantation without DST, recurrence of proteinuria in LEW.1W kidneys appeared at approximately 10 days, possibly associated with rejection of the graft. In the same combination with DST, proteinuria occurred after 20 days, and the attendant glomerular damage suggested that the initial kidney disease had recurred. Transplanted control animals remained free of proteinuria. In the opposite combination, the proteinuria and the lesions of Buffalo/Mna kidneys regressed after transplantation into healthy LEW.1W rats. The recurrence of proteinuria after transplantation in Buffalo/Mna and the remission of lesions in Buffalo/Mna kidneys transplanted into normal hosts suggests that Buffalo/Mna rats express circulating albuminuric factors, which may be relevant to the relapse of idiopathic nephrotic syndrome in humans.