TY  - JOUR
AU  - Wei, C.
AU  - El Hindi, S.
AU  - Li, J.
AU  - Fornoni, A.
AU  - Goes, N.
AU  - Sageshima, J.
AU  - Maiguel, D.
AU  - Karumanchi, S.A.
AU  - Yap, H.-K.
AU  - Saleem, M.
AU  - Zhang, Q.
AU  - Nikolic, B.
AU  - Chaudhuri, A.
AU  - Daftarian, P.
AU  - Salido, E.
AU  - Torres, A.
AU  - Salifu, M.
AU  - Sarwal, M.M.
AU  - Schaefer, F.
AU  - Morath, C.
AU  - Schwenger, V.
AU  - Zeier, M.
AU  - Gupta, V.
AU  - Roth, D.
AU  - Rastaldi, M.P.
AU  - Burke, G.
AU  - Ruiz, P.
AU  - Reiser, J.
T1  - Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis
LA  - eng
PY  - 2011
SP  - 952
EP  - 960
T2  - Nature Medicine
SN  - 1078-8956
VL  - 17
IS  - 8
AB  - Focal segmental glomerulosclerosis (FSGS) is a cause of proteinuric kidney disease, compromising both native and transplanted kidneys. Treatment is limited because of a complex pathogenesis, including unknown serum factors. Here we report that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primary FSGS, but not in people with other glomerular diseases. We further find that a higher concentration of suPAR before transplantation underlies an increased risk for recurrence of FSGS after transplantation. Using three mouse models, we explore the effects of suPAR on kidney function and morphology. We show that circulating suPAR activates podocyte β3 integrin in both native and grafted kidneys, causing foot process effacement, proteinuria and FSGS-like glomerulopathy. Our findings suggest that the renal disease only develops when suPAR sufficiently activates podocyte β3 integrin. Thus, the disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by interfering with the suPAR-2 3 integrin interaction through antibodies and small molecules targeting either uPAR or β3 integrin. Our study identifies serum suPAR as a circulating factor that may cause FSGS. © 2011 Nature America, Inc. All rights reserved.
DO  - 10.1038/NM.2411
UR  - https://portalciencia.ull.es/documentos/5e39b7e62999523aa927176a
DP  - Dialnet - Portal de la Investigación
ER  -