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 . 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.