Abstract
The renal response to acute hyperkalemia is mediated by increased K(+) secretion within the connecting tubule (CNT), flux that is modulated by tubular effects (e.g., aldosterone) in conjunction with increased luminal flow. There is ample evidence that peritubular K(+) blunts Na(+) reabsorption in the proximal tubule, thick ascending Henle limb, and distal convoluted tubule (DCT). Although any such reduction may augment CNT delivery, the relative contribution of each is uncertain. The kidney model of this laboratory was recently advanced with representation of the cortical labyrinth and medullary ray. Model tubules capture the impact of hyperkalemia to blunt Na(+) reabsorption within each upstream segment. However, this forces the question of the extent to which increased Na(+) delivery is transmitted past the macula densa and its tubuloglomerular feedback (TGF) signal. Beyond increasing macula densa Na(+) delivery, peritubular K(+) is predicted to raise cytosolic Cl(-) and depolarize macula densa cells, which may also activate TGF. Thus, although the upstream reduction in Na(+) transport may be larger, it appears that the DCT effect is critical to increasing CNT delivery. Beyond the flow effect, hyperkalemia reduces ammoniagenesis and reduced ammoniagenesis enhances K(+) excretion. What this model provides is a possible mechanism. When cortical [Formula: see text] is taken up via peritubular Na(+)-K(+)([Formula: see text])-ATPase, it acidifies principal cells. Consequently, reduced ammoniagenesis increases principal cell pH, thereby increasing conductance of both the epithelial Na(+) channel and renal outer medullary K(+) channel, enhancing K(+) excretion. In this model, the effect of aldosterone on principal cells, diminished DCT Na(+) reabsorption, and reduced ammoniagenesis all provide relatively equal and additive contributions to renal K(+) excretion.NEW & NOTEWORTHY Hyperkalemia blunts Na(+) reabsorption along the nephron, and increased CNT Na(+) delivery facilitates K(+) secretion. The model suggests that tubuloglomerular feedback limits transmission of proximal effects past the macula densa, so that it is DCT transport that is critical. Hyperkalemia also reduces PCT ammoniagenesis, which enhances K(+) excretion. The model suggests a mechanism, namely, that reduced cortical ammonia impacts CNT transport by raising cell pH and thus increasing both ENaC and ROMK conductance.