The glomerular permeability factors in idiopathic nephrotic syndrome.
It is currently postulated that steroid-sensitive idiopathic nephrotic syndrome (SSNS) and steroid-resistant idiopathic nephrotic syndrome (SRNS), which are not related to the mutation of a gene coding for podocyte structures or for glomerular basement membrane proteins, result from a circulating factor affecting podocyte shape and function. T lymphocytes have for a long time been suspected to be involved in the pathophysiology of these diseases. The successful treatment of steroid-dependant nephrotic syndrome with rituximab suggests a potential role for B lymphocytes. Clinical and experimental data indicate roles for cytokines IL-13, TNFα, circulating cardiotrophin-like cytokine factor 1 (member of the IL-6 family), circulating hemopexin, radical oxygen species, and the soluble urokinase-type plasminogen activator receptor (suPAR) in the development of nephrotic syndrome. Podocyte metabolism modifications-leading to the overexpression of the podocyte B7-1antigen (CD 80), hypoactivity of the podocyte enzyme sphingomyelin phosphodiesterase acid-like 3 b (SMPDL3b), and to the podocyte production of a hyposialylated form of the angiopoietin-like 4 (Angptl4)-are mechanisms possibly involved in the changes in the podocyte cytoskeleton leading to SSNS and or SRNS. Different multifactorial pathophysiological mechanisms can be advocated for SSNS and SRNS. The present paper reviews the experimental and clinical data upon which the different hypotheses are based and reports their possible clinical applications.
Emma Children's Hospital/ Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. j.c.davin@amc.uva.nl.|Queen Fabiola Academic Children's Hospital, Free University of Brussels, Brussels, Belgium. j.c.davin@amc.uva.nl.|Pediatric Nephrology Department, Emma Children's Hospital/ Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. j.c.davin@amc.uva.nl.
Jean-Claude
JC
Davin
D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D009404:Nephrotic Syndrome / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D010539:Permeability; D050199:Podocytes / Q000378:metabolism*
Circulating factors; Glomerular permeability factors; Nephrotic syndrome; Podocyte; Proteinuria