5/6 Nephrectomy Impairs Acute Kaliuretic Responses and Predisposes to Postprandial Hyperkalemia

The susceptibility of patients with chronic kidney disease (CKD) to develop postprandial hyperkalemia suggests alterations in normal kidney sodium (Na + ) and potassium (K + ) handling, but the exact nature of these changes is largely unknown. To address this, we analyzed the natriuretic and kaliuretic responses to diuretics and acute K + loading in rats who underwent 5/6 nephrectomy (5/6Nx) and compared this to the response in sham-operated rats. The natriuretic and kaliuretic responses to furosemide, hydrochlorothiazide, and amiloride were largely similar between 5/6Nx and sham rats except for a significantly reduced kaliuretic response to hydrochlorothiazide in 5/6Nx rats. Acute dietary K + loading with either 2.5% potassium chloride or 2.5% potassium citrate caused lower natriuretic and kaliuretic responses in 5/6Nx rats compared with sham rats. This resulted in significantly higher plasma K + concentrations in 5/6Nx rats which were accompanied by corresponding increases in plasma aldosterone. Acute K + loading caused dephosphorylation of Ste20-related proline/alanine-rich kinase (SPAK) and the sodium-chloride cotransporter (NCC) both in sham and 5/6Nx rats. In contrast, the acute K + load decreased the Na + /hydrogen exchanger 3 (NHE3) and increased serum- and glucocorticoid-regulated kinase 1 (SGK1) and the α-subunit of the epithelial sodium channel (ENaC) only in sham rats. Together, our data show that 5/6Nx impairs the natriuretic and kaliuretic response to an acute dietary K + load which is further characterized by a loss of ENaC adaptation and the development of postprandial hyperkalemia.