Nephrotic syndrome is associated with increased plasma K+ concentration, intestinal K+ losses, and attenuated urinary K+ excretion: a study in rats and humans

The present study tested the hypotheses that nephrotic syndrome (NS) leads to renal K+ loss because of augmented epithelial Na+ channel (ENaC) activity followed by downregulation of renal K+ secretory pathways by suppressed aldosterone. The hypotheses were addressed by determining K+ balance and kidney abundance of K+ and Na+ transporter proteins in puromycin aminonucleoside (PAN)-induced rat nephrosis. The effects of amiloride and angiotensin II type 1 receptor and mineralocorticoid receptor (MR) antagonists were tested. Glucocorticoid-dependent MR activation was tested by suppression of endogenous glucocorticoid with dexamethasone. Urine and plasma samples were obtained from pediatric patients with NS in acute and remission phases. PAN-induced nephrotic rats had ENaC-dependent Na+ retention and displayed lower renal K+ excretion but elevated intestinal K+ secretion that resulted in less cumulated K+ in NS. Aldosterone was suppressed at day 8. The NS-associated changes in intestinal, but not renal, K+ handling responded to suppression of corticosterone, whereas angiotensin II type 1 receptor and MR blockers and amiloride had no effect on urine K+ excretion during NS. In PAN-induced nephrosis, kidney protein abundance of the renal outer medullary K+ channel and γ-ENaC were unchanged, whereas the Na+-Cl− cotransporter was suppressed and Na+-K+-ATPase increased. Pediatric patients with acute NS displayed suppressed urine Na+-to-K+ ratios compared with remission and elevated plasma K+ concentration, whereas fractional K+ excretion did not differ. Acute NS is associated with less cumulated K+ in a rat model, whereas patients with acute NS have elevated plasma K+ and normal renal fractional K+ excretion. In NS rats, K+ balance is not coupled to ENaC activity but results from opposite changes in renal and fecal K+ excretion with a contribution from corticosteroid MR-driven colonic secretion.

EFFECT OF CHRONIC RENAL DYSFUNCTION ON THE PERMEABILITY OF THE COLON TO WATER AND ELECTROLYTES: EXPERIMENTAL STUDY IN RATS

ABSTRACT Background: Renal insufficiency is a disease that affects several organs by provoking hypervolemia and uremia. The disease reaches more than 500 million people worldwide and few studies bring their influence on the gastrointestinal tract. Aim: To evaluate the influence of 5/6 nephrectomy-induced hypervolemia on colonic permeability to water and electrolytes. Method: Sixty male Wistar rats weighing between 280-300 g were divided into three groups: 3, 7 and 14 days after nephrectomy, each one having a false-operated/control and partially nephrectomized. For colonic permeability they were submitted to colonic perfusion with a solution of Tyroad containing phenolphthalein. Differences among the concentrations of Na+, K+ and Cl- were used to calculate the rate of colonic permeability for the electrolytes. Phenolphthalein concentrations were used to evaluate the rate of secretion and water absorption. Results: The colonic secretion of water and electrolytes occurred expressively in the group seven days after nephrectomy. Hemodynamic and biochemical assessments determined the progression of renal failure in all three groups and polyethylene glycol was shown to be effective in reversing the secretory capacity of the colon. Conclusion: Hypervolemia established after 7 days post-nephrectomy 5/6 caused marked colonic secretion for water and electrolytes. The organism presents progressive colonic secretion as the blood volume increases; on the other hand, polyethylene glycol was able to revert this secretory framework of the colon to water and electrolytes by reversing the hypervolemia.