Introduction Interstitial edema is a common clinical feature of nephrotic syndrome (NS). It is often massive (up to 30% of body weight) and constitutes a functional constraint, owing to locomotive restriction and eyelid shutting. Expansion of the interstitial compartment volume results from the combination of abnormal renal sodium retention and alterations of fluid transfer across capillary walls. Renal retention of sodium in nephrotic syndrome Site of sodium retention 1 2 3 3 4 1 5 6 8 Cellular mechanism of sodium retention in the collecting duct 5 4 1 4 1 9 10 11 13 1 14 11 13 13 Fig. 1 ENaC top panels left panel asterisk T P right panel bottom panels left panel asterisk G 13 14  Aldosterone and activation of mineralo-corticoid receptors are not involved in sodium retention in nephrotic syndrome 15 13 16 17 18 19 20 21 22 23 11 13 None of the known factors that control sodium reabsorption in the collecting duct accounts for sodium retention in PAN-nephrotic rats 24 25 26 27 28 29 30 31 32 33 2 Fig. 2 dotted lines solid lines Arrows grey boxes  Na,K-ATPase is the primary target of sodium retention in PAN nephrosis 13 11 13 13 1 Edema formation in nephrotic syndrome 34 \documentclass[12pt]{minimal}
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\begin{document}$$ {\text{J}}_{{\text{v}}}  = {\text{L}}_{{\text{p}}}  \times {\text{S}} \times {\left[ {{\left( {{\text{P}}_{{\text{c}}}  - {\text{P}}_{{\text{i}}} } \right)} - \sigma  \times {\left( {\Pi _{{\text{c}}}  - \Pi _{{\text{i}}} } \right)}} \right]} $$\end{document} v p c i c i v c i 16 35 35 36 37 37 38 c i 34 39 40 p 34 p 41 42 p 43 44 p 45 The reflexion coefficient of proteins (σ) is increased in NS 46 47 Therapeutic implications Nephrotic edema results from the combination of renal sodium retention and increased capillary permeability. Although treatment of either of these two alterations would prevent edema, treatment of capillary permeability alone would lead to hypertension. Thus, treatments of edema must primarily target renal sodium retention. 5 48 49 50 5 21 Conclusion Whatever their etiology, nephrotic syndromes are always associated with renal retention of sodium. Renal sodium retention results from enhanced sodium reabsorption along the connecting and cortical collecting ducts and from blunted responsiveness of medullary collecting ducts to the natriuretic response to atrial natriuretic peptide. Induction of de novo synthesis of Na,K-ATPase is the primary effector of increased sodium reabsorption. It is not accounted for by any circulating factor, in particular aldosterone, known to stimulate sodium reabsorption along the distal nephron. New research strategies will be required to identify the unknown regulatory pathway that is dysregulated in NS. Sodium retention in NS does not lead to high blood pressure but leads to an asymmetric expansion of the interstitium, while the vascular volume remains unchanged in most patients. This asymmetry of extracellular volume expansion is accounted for by changes in the intrinsic properties of the endothelial capillary barriers, i.e., an increase in its hydraulic conductivity and permeability to proteins, rather than to an imbalance of Starling’s forces. 51