Pathophysiology and management of hyperkalemia in the neonate

Intestinal potassium handling

Dietary [K] is 90% absorbed in the gastrointestinal tract, primarily in the small intestine. When renal excretion of [K] is limited, the colon (which under normal conditions plays a minimal role in absorption and secretion of K) acquires a more prominent role. The messenger RNA encoding the colonic alpha isoform of the H-K-ATPase ^, upregulates in conditions that favor [K] absorption.

The kidney is the major regulator of extracellular (EC) [K]. A chronic oral [K] load is needed to cause a significant rise in EC potassium. This increases [K] secretion in the distal nephron mediated by aldosterone. Conversely, limited [K] intake inhibits aldosterone.

Minor changes in dietary [K] can induce kaliuresis without hyperkalemia or changes in aldosterone. Increase in [K] in the splenic circulation stimulates local sensors that can directly induce a kaliuretic response through a phenomenon known as the feedforward mechanism. This effect is blunted by loop diuretics such as bumetanide, suggesting that an Na-K-Cl cotransporter in the hepatoportal system signals the kidneys and consequently causes kaliureisis. ^, With low potassium intake the inverse occurs, possibly due to sensors in the gastric or hepatoportal circulation inactivating renal outer medullary [K] channels (ROMK).

A positive [K] balance is necessary in neonates for somatic growth. This is achieved via maximal intestinal absorption of [K] and decreased renal excretion. There are experimental data demonstrating that the immature intestine absorbs [K] more avidly because of lower activity of the basolateral Na-K-ATPase and increased activity of apical [K] absorptive pumps (H-K-ATPase and Na-independent K-ATPase). As a consequence, a lower IC [K] promotes intestinal absorption in the neonate vs. secretion in the adult colon. This results in total body [K] retention with higher EC [K] in the neonate. ^,

Extrarenal potassium regulation

The [K] that is absorbed is rapidly shifted into the IC compartment preventing a dangerous rise in plasma [K]. This is due to coordination between active uptake by cells via Na-K-ATPase pump (principally in skeletal muscle) and passive back leak of [K] from the cells through [K] channels. This mechanism is not fully developed in preterm neonates. Premature infants with hyperkalemia exhibit lower Na-K-ATPase activity associated with lower IC K–to–serum [K] ratios when compared to normokalemic premature infants. These immature mechanisms are the most likely cause of nonoliguric hyperkalemia of premature infants, defined as a plasma [K ⁺ ] higher than 6.5 mEq/L within the first 72 hours of life in very low birth weight (birth weight lower than 1500 g) or very preterm (less than 32 weeks’ postmenstrual age) infants in the presence of normal renal function for age.

ß2 agonist and insulin regulate [K] by increasing IC uptake via stimulation of Na-K-ATPase pump, primarily in the skeletal muscle. Metabolic acidosis reduces the activity of Na-K-ATPase decreasing [K] entry to the cell.

Renal potassium regulation

Potassium is freely filtered in the glomerulus. In the mature kidney 60%–70% is absorbed in the proximal tubule with sodium, chlorine, and fluid. At the thick ascending limb of the loop of Henle another 25% is reabsorbed primarily via Na-K-2Cl cotransporter. Immature kidneys preserve K. Studies in humans have shown the ability of children to excrete a [K] load is decreased until 10–11 years of age. This is important to ensure somatic growth.