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

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Abstract

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.

Authors

Ludmilla Le Berre, Yann Godfrin, Eberhard Günther, Françoise Buzelin, Sabine Perretto, Helga Smit, Dontscho Kerjaschki, Claire Usal, Cristina Cuturi, Jean-Paul Soulillou, Jacques Dantal