The pathophysiology of edema formation in the nephrotic syndrome Eric C. Siddall, Jai Radhakrishnan  Kidney International  Volume 82, Issue 6, Pages 635-642 (September 2012) DOI: 10.1038/ki.2012.180 Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 1 As serum oncotic pressure declines, there is a parallel decline in interstitial oncotic pressure of greater magnitude in rats fed a very low protein diet . (adapted from Fiorotto and Coward 7) Kidney International 2012 82, 635-642DOI: (10.1038/ki.2012.180) Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 2 Plasminogen filtered by the nephrotic glomeruli is converted to plasmin by urokinase-type plasminogen activator in the cortical collecting duct cells. Plasmin then proteolytically removes the γ inhibitory domain from epithelial sodium channel (ENaC), resulting in near full activation of ENaC. Kidney International 2012 82, 635-642DOI: (10.1038/ki.2012.180) Copyright © 2012 International Society of Nephrology Terms and Conditions

Figure 3 Mechanisms of sodium retention in the nephrotic syndrome. (1) Increased angiotensin II-independent afferent and efferent arteriolar tone because of increased efferent sympathetic nerve activity. (2) Tubular resistance to atrial natriuretic peptide (ANP). (3) Increased number of open epithelial sodium channel (ENaC) channels in the cortical collecting duct due to proteolytic activation of ENaC by plasmin. (4) Increased number and activity of cortical collecting duct Na/K ATPase channels. SNS, sympathetic nervous system. Kidney International 2012 82, 635-642DOI: (10.1038/ki.2012.180) Copyright © 2012 International Society of Nephrology Terms and Conditions