Nephrotic Syndrome: Pathophysiology update

Why does edema happen in nephrotic syndrome?

There has been talk about this topic for decades. There is the underfill and the overfill concepts and both have had their share of evidence for and against it. A recent article in Kidney International describes the journey through the different players in the formation of edema in nephrotic syndrome.

Take home points that the article suggests after review of the basic science and clinical literature.

1. Hypoalbuminemia is not a cause of edema formation in nephrotic syndrome
2. Vascular permeability abnormalities are also less likely the major players
3. Proteinuria leads to increased activation of ENAC channels and leading to Na retention- this might be the major cause of edema. This might be the most active component regardless of the intravascular volume status of the patient.
4. Excess serum ADH levels might also help in water retention.
5. RAS system does not appear to be the primary mechanism of renal Na retention.

This leads us to believe that perhaps a combination of loop diuretic + K sparing diuretics might be a good combination to use in the treatment of the edema( although data is sparse)

Some interesting points from the article regarding edema physiology

1. Extracellular fluid volume expansion excess expands both the intravascular and interstitial space in chronic renal failure compared to nephrotic syndrome- where its largely confined to the interstitial space due to protective effects of interstitial protein washdown and washout.
2. Minimal Change disease or severe hypoalbuminemia might have true decrease in intravascular volume compared to other nephrotic syndromes that are more in the range of normal to expanded blood volume.