Why does nephrotic syndrome cause edema

A father's gift to his son Father's Day will be extra-special this year for the Teeples family in La Crosse, Wisconsin. Share on: Facebook Twitter. Show references Ferri FF. Nephrotic syndrome. In: Ferri's Clinical Advisor Elsevier; Accessed Nov. Nephrotic syndrome in adults. Kelepouris E, et al. Overview of heavy proteinuria and the nephrotic syndrome. A to Z health guide: Nephrotic syndrome.

The intrarenal mechanism responsible for primary sodium retention is not yet known, but may involve tubular resistance to the natriuretic effect of atrial natriuretic peptide. Abstract The development of edema in the nephrotic syndrome has traditionally been viewed as an underfill mechanism.

Furthermore the gradient in colloid osmotic pressure between serum and interstitium tends to be preserved in nephrotic syndrome. The distribution of excess extracellular fluid is markedly different in patients with nephrotic syndrome from that seen in patients who have reduced glomerular filtration rate as the cause of sodium retention.

This is not fully understood but hypotheses centre on capillary permeability and colloid osmotic pressure effects. Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription. Please subscribe or login to access full text content. If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

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Publications Pages Publications Pages. The hypothesis suggests the following sequence of events Figure 1 : urinary loss of proteins in NS, especially albumin, causing hypoalbuminaemia, which in turn causes a decrease in plasma oncotic pressure. This decrease in plasma oncotic pressure would then cause an imbalance in Starling forces, resulting in the movement of fluid from the intravascular space to the interstitial space, causing a decrease in effective arterial blood volume and consequently, relative hypovolaemia.

This would then result in activation of the renin-angiotensin-aldosterone and sympathetic nervous systems, increased antidiuretic hormone release and inhibition of atrial natriuretic peptide release. Activation of these systems would cause sodium and water retention in the kidneys, with subsequent oedema. However, several experimental and clinical observations made over the years do not support this hypothesis.

Patients and laboratory rats with low serum albumin levels do not develop oedema or sodium retention. Joles et al 3 measured the plasma and interstitial oncotic pressure of Nagase rats, which are mutant rats characterised by analbuminaemia.

The researchers found no signs of sodium retention in those animals. Furthermore, Lecomte et al 4 carried out observations on patients with congenital analbuminaemia and found that most had no oedema. Many other published series of patients with congenital analbuminaemia do not report the appearance of oedema as the main symptom. Of these 24 patients, only six had oedema. These six patients with oedema had an alternative diagnosis that clearly explained the presence of oedema cor pulmonale.

During the study, they found some patients with serum albumin levels below 1. Natriuresis in the recovery phase of nephrotic syndrome begins when proteinuria disappears but before serum albumin returns to normal levels 7.

The absolute decrease in plasma oncotic pressure does not affect the volume of the intravascular space in nephrotic syndrome. Studies performed on dogs suggest that the absolute decrease in plasma oncotic pressure would not affect plasma or blood volume.

During this time, the oncotic pressure gradient between plasma and interstitium was constant. Plasma and blood volumes are normal or increased in nephrotic syndrome. Geers et al 10 measured plasma volumes in 88 patients with NS and in 51 controls.

Plasma volume was measured by administration of radioactive albumin I. Intravascular space expansion with albumin does not increase natriuresis in patients with nephrotic syndrome. The effect of an intravenous infusion of hyperoncotic albumin 75g was observed in patients with NS. Plasma renin activity and serum aldosterone concentration decreased to the point of being suppressed. Urinary sodium excretion did not change significantly. The activation of the renin-angiotensin-aldosterone system is not involved in the development of oedema in nephrotic syndrome.

Brown et al 12, administered captopril to a group of NS patients and observed no change in sodium excretion despite suppressing serum aldosterone concentrations.

In another study, Usberti et al 13 reported similar findings when using spironolactone. Adrenalectomy does not prevent sodium retention and the development of ascites in nephrotic syndrome in laboratory rats. De Seigneux et al studied a group of rats from which they had removed both adrenal glands. The rats were administered dexamethasone to prevent adrenal failure.

The rats developed oedema and sodium retention despite having been adrenalectomised. These findings suggest that aldosterone does not play a major role in sodium retention that is characteristic of NS. Contrary to the classic hypothesis, the alternative hypothesis also called the overfill hypothesis postulates that sodium retention in many NS patients is a primary renal phenomenon and may be caused by an intrinsic renal defect in sodium excretion, which in turn causes an expansion in plasma volume hence the term overfill.

Although the molecular mechanism of sodium retention in the kidneys has not been clearly explained, there are a number of studies on this topic, which we describe below.

Molecular mechanisms of sodium retention in nephrotic syndrome. The first observations supporting the overfill hypothesis were made by Chandra 15 and Ichikawa. When PAN is administered to rats, it causes massive proteinuria and sodium retention. The renal histopathology induced by PAN resembles minimal change disease. The unilateral NS model allows the study of a proteinuric kidney and a control kidney in the same animal. It must be emphasised that the sodium retention by the kidney perfused with PAN occurred without a reduction in plasma protein concentration, suggesting that the sodium retention observed in NS was due to an intrinsic renal defect in sodium excretion rather than due to extrinsic or systemic factors such as hypoalbuminaemia.

The cortical collecting tubule is the reabsorption point for sodium in nephrotic syndrome. Ichikawa 16 also performed micropuncture studies of superficial nephron tubular segments in the unilateral NS model in rats, and showed that the amount of sodium at the end of the distal convoluted tubule is the same in the proteinuric kidney as in the normal kidney.

The final urine of the nephrotic kidney, however, contained three times less sodium than the urine from the normal kidney, suggesting that stimulation of sodium reabsorption in the NS occurs in the cortical collecting tubule. Despite the findings of Ichikawa et al, other studies have postulated that sodium retention in NS may occur in other nephron segments.

Sixty-six percent of sodium filtered by the glomerulus is reabsorbed in the proximal tubule by the action of the Na-H cotransporter NHE3. It would be reasonable then to assume that this segment would, at least in part, contribute to the sodium retention observed in NS.

NHE3 is present at two locations of the proximal tubular brush border, forming oligomers: 1 in the intervillous space, where it is associated with the megalin receptor a protein responsible for the reabsorption of albumin and other substances filtered by the glomerulus , representing the inactive form of NHE3, and 2 in the microvillous space, where it is free and represents the active form of the transporter.

Deschenes et al 24 found that the activity of this pump was increased in rats treated with PAN when compared to control rats.