Hyponatremia in the Dialysis Population

Abstract

Sodium derangements are among the most frequently encountered electrolyte disorders in patients with end-stage renal disease. As dialysis patients are predisposed to hyponatremia via multiple pathways, assessment of extracellular volume status is an essential first step in disentangling potential etiologic factors. In addition, multiple large population-based studies indicate that proxies of malnutrition (e.g., low body mass index, serum albumin, and serum creatinine levels) and loss of residual kidney function are important determinants of hyponatremia in dialysis patients. Among hemodialysis and peritoneal dialysis patients, evidence suggests that incrementally lower sodium levels are associated with increasingly higher death risk, highlighting the long-term risk of hyponatremia. Whereas in conventional survival models incrementally lower serum sodium concentrations are associated with worse mortality in hemodialysis patients, studies that have examined repeated measures of predialysis sodium have demonstrated mixed associations of time-varying sodium with higher mortality risk (i.e., U-shaped vs. inverse linear relationships). Although the causality of the hyponatremia-mortality association in dialysis patients remains uncertain, there are several plausible pathways by which lower sodium levels may lead to higher death risk, including central nervous system toxicity, falls and fractures, infection-related complications, and impaired cardiac function. Areas of uncertainty ripe for future studies include the following: (i) mechanistic pathways by which lower serum sodium levels are linked with higher mortality in dialysis patients, (ii) whether correction of sodium derangements improves outcomes, (iii) the optimal sodium target, and (iv) the impact of age and other sociodemographic factors on hyponatremia-outcome associations.

Keywords: hemodialysis; hyponatremia; mortality risk; peritoneal dialysis; sodium; survival model.

Figure 1

Risk factors for hyponatremia in dialysis patients. Upward-pointing arrow = increased; downward-pointing arrow = decreased. ADH, antidiuretic hormone; CAPD, continuous ambulatory peritoneal dialysis; ECV, extracellular volume; H₂O, water; K, potassium; PO, oral; RKF, residual kidney function; UF, ultrafiltration; WT, weight.

Figure 2

Association of baseline (a) and time-varying (b) serum sodium levels and mortality in hemodialysis patients. Association of baseline (c) and time-varying (d) serum sodium levels and mortality in peritoneal dialysis patients. CI, confidence interval; HR, hazard ratio; IDWG, interdialytic weight gain. Adapted from Ravel et al. and Rhee et al.

Figure 3

Varying scenarios of the interrelationship between serum sodium and mortality in dialysis patients (a). Low serum sodium as a mechanistic link between loss of residual kidney function and higher mortality risk (b). Upward-pointing arrow = increased; downward-pointing arrow = decreased. PEW, protein-energy wasting.

Figure 4

Potential mechanisms underlying the relationship between hyponatremia and mortality. Downward-pointing arrow = decreased. CNS, central nervous system; CV, cardiovascular; IL, interleukin.