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Pathophysiology and treatment of edema in patients with the nephrotic syndrome

Jai Radhakrishnan, MD, MS
Section Editors
Richard J Glassock, MD, MACP
Fernando C Fervenza, MD, PhD
Deputy Editor
Albert Q Lam, MD


Edema is one of the major clinical manifestations of the nephrotic syndrome. The pathophysiology and treatment of edema in patients with the nephrotic syndrome will be reviewed here. More general issues such as the clinical manifestations, diagnosis, and general principles of the treatment of edema are discussed elsewhere as is the mechanism of hypoalbuminemia in the nephrotic syndrome. (See "Clinical manifestations and diagnosis of edema in adults" and "General principles of the treatment of edema in adults" and "Overview of heavy proteinuria and the nephrotic syndrome", section on 'Hypoalbuminemia'.)


Two major factors, both of which lead to retention, have been thought to be responsible for the development of edema in patients with the nephrotic syndrome; it is likely that both contribute to a variable degree in individual patients [1,2]:

Primary sodium retention that is directly induced by the renal disease (overfill hypothesis)

Secondary sodium retention in which the low plasma oncotic pressure due to hypoalbuminemia promotes the movement of fluid from the vascular space into the interstitium, leading to underfilling of the vasculature and activation of the renin-angiotensin-aldosterone system (underfill hypothesis)

The clinical importance of distinguishing between these mechanisms is the ability to tolerate diuretic therapy. Diuretics are well tolerated in patients with renal sodium retention but, if underfilling is the primary mechanism, can lead to worsening hypovolemia as evidenced clinically by an elevation in serum creatinine. As will be described below, most patients tolerate diuretic therapy at least initially.

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Literature review current through: Nov 2017. | This topic last updated: May 19, 2017.
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