Nephrotic Syndrome


Other factors which may be involved in sodium retention

Other possible factors involved in sodium retention in nephrotic syndrome:

  • Vasopressin - Through activation of V2 receptors, vasopressin increases sodium reabsorption in the collecting duct synergistically with aldosterone.
  • Angiotensin II - Through stimulation of AT1 receptors, angiotensin II increases sodium reabsorption, independently of aldosterone release.
  • Insulin-like growth factor I (IGF-I) - IGF-1 can induce sodium retention and oedema, probably through stimulation of sodium reabsorption in the collecting duct.
  • Tumor necrosis factor α (TNFα) - TNFα increases expression of Na+K+ATPase and administration of the TNFα receptor blocker, etanercept to rats induces a natriuresis.
  • Peroxisome proliferator-activated receptor γ (PPARγ) - PPARγ agonists have been shown to induce sodium retention via a stimulatory effect on the collecting ducts.
  • Nitric oxide - Inhibition of nitric oxide synthase promotes sodium excretion in cirrhotic rats with ascites.

If strategies are used to block these possible effector pathways, the only one which has been found to have an effect on sodium retention is that acting upon angiotensin II.  The AT1 blocker, irbesartan was able to improve sodium excretion, but only during the early phase of sodium retention.

It is possible to induce heavy proteinuria in just one kidney in the PAN-induced rat model. When this is done, only the treated kidney retains sodium, indicating that a systemic factor is not involved. It suggests that there is a direct effect of PAN on the collecting duct, or a unidentified factor in the luminal fluid acts upon the distal nephron.

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