Changes in renal sodium transport during a systemic inflammatory response

Abstract

Sirs, Watanabe et al. [1] reported on the clinical characteristics of patients with hyponatremia in Kawasaki disease (KD). They noted that hyponatremia was associated with a more severe systemic inflammatory response reflected in prolonged pyrexia and higher C-reactive protein levels. We have recently published the result of a prospective study investigating changes in systemic sodium and chloride transport in meningococcal septicemia. Severe meningococcal septicemia was associated with increased fractional renal sodium excretion [2]. Both meningococcal septicemia and Kawasaki disease are associated with an intensive systemic inflammatory response with high circulating levels of interleukin-1 (IL-1) and tumor necrosis factor (TNF) [3– 6]. The mechanism by which these inflammatory mediators are able to induce hyponatremia has been investigated in both animal studies and in vitro. It involves increased renal sodium loss by a reduction in renal tubular sodium absorption. Inflammatory mediators like IL-1 and TNF have been shown to reduce epithelial sodium transport in epithelial cells by a reduction of the expression and function of the apical epithelial sodium channel (ENaC) and/or the sodium potassium ATPase (Na/K ATPase) at the basolateral membrane [7]. IL-1 was hereby found to induce natriuresis in the rat model [8]. The mechanism was investigated in cultures of inner medullary, cortical collecting duct and proximal tubular renal cells in vitro and it was found to involve a reduction of the Na/K ATPase function. The effect was mediated by prostaglandin E2 and inhibitable by the cyclooxygenase inhibitor indomethacin [9–13]. Another pathway by which IL-1 and TNF are involved in a reduction of renal sodium absorption is by increasing tissue levels of nitric oxide, which is a potent suppressor of the epithelial Na/K ATPase function mediated by the intracellular messenger cGMP and via modification of protein kinase G [14, 15]. Future studies into the etiology of hyponatremia in KD need to investigate the effects of therapies directed at a reduction of effects of IL-1 and TNF and their mediators PGE2 and NO on renal fractional sodium excretion and hyponatremia.