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Nephrol Dial Transplant. 2014 Dec;29(12):2207-16. doi: 10.1093/ndt/gfu355.

Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future.

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Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.


The term idiopathic nephrotic syndrome (iNS) traditionally covers minimal change disease and primary focal segmental glomerulosclerosis (FSGS), now thought to be separate disease entities. Clinical and experimental evidence suggest that circulating permeability factors are involved in their pathogenesis. In the past four decades, many investigators have searched for the responsible factors, thus far with little success. The recent report of the soluble urokinase plasminogen activator receptor as a causative factor in FSGS has received much attention, but again the initially promising findings were not confirmed. We describe the history of the search for permeability factors, discuss the pitfalls that are likely responsible for the lack of success and propose criteria that should be used in future studies when evaluating candidate permeability factors.


focal segmental glomerulosclerosis; idiopathic nephrotic syndrome; minimal change disease; permeability factor; suPAR

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