While administration of Hypertonic Saline (HSS) in combination with diuretics has yielded improved weight loss, preservation of renal function, and reduction in hospitalization time in the clinical setting of patients with acute decompensated heart failure (ADHF), the mechanisms that underlie these beneficial effects remain unclear and additional studies are needed before this approach can be adopted on a more consistent basis. As high salt conditions stimulate production of several renal autacoids that exhibit natriuretic effects, renal physiologists can contribute to the understanding of mechanisms by which HSS leads to increased diuresis both as an individual therapy, as well as in combination with loop diuretics. For instance, since HSS increases TNF-α production by proximal tubule (PT) and thick ascending limb of Henle's loop (TAL) epithelial cells, this 'Perspective article' is aimed at highlighting how the effects of TNF-α produced by these cell types may contribute to the beneficial effects of HSS in patients with ADHF. While TNF-α produced by infiltrating macrophages and T cells exacerbate and attenuate renal damage, respectively, production of this cytokine within the tubular compartment of the kidney functions as an intrinsic regulator of blood pressure and sodium homeostasis via mechanisms along the nephron related to inhibition of NKCC2 activity and angiotensinogen (AGT) expression. Thus, in the clinical setting of ADHF and hyponatremia, induction of TNF-α production along the nephron by administration of HSS may attenuate NKCC2 activity and AGT expression as part of a mechanism that prevents excessive Na+ reabsorption in the TAL, thereby mitigating volume overload.
Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure: A U.S. Center's Experience