Urine Sodium Excretion After Tolvaptan Administration Is Dependent Upon Baseline Serum Sodium Levels

Abstract

SummarySeveral studies have demonstrated that tolvaptan (TLV) can improve hyponatremia in advanced heart failure (HF) patients with rare chance of hypernatremia. However, changes in serum sodium concentrations (S-Na) in patients with or without hyponatremia during TLV treatment have not been analyzed.Ninety-seven in-hospital patients with decompensated HF who had received TLV at 3.75-15 mg/day for 1 week were enrolled. Among 68 "responders", who had achieved any increases in urine volume (UV) during the fi rst day, urinary sodium excretion during 24 hours (U-NaEx 24 ) increased signifi cantly during one week of TLV treatment along with higher baseline S-Na (P < 0.05 and r = 0.325). Considering a cut-off value (S-Na, 132 mEq/L; AUC, 0.711) for any increases in U-NaEx 24 , we defi ned "hyponatremia" as S-Na < 132 mEq/L. In hyponatremic responders (n = 25), S-Na increased signifi cantly, although 1 week was not suffi cient for normalization (125.8 ± 5.0 versus 128.9 ± 4.3 mEq/L, P < 0.05), along with unchanged U-NaEx 24 (2767 ± 2703 versus 2972 ± 2950 mg/day, NS). In contrast, in normonatremic responders (n = 43), S-Na remained unchanged (136.6 ± 3.1 versus 137.4 ± 2.9 mEq/L, NS) along with increased UNaEx 24 (2201 ± 1644 versus 4198 ± 3550 mg/day, P < 0.05).TLV increased S-Na only in hyponatremic responders by way of pure aquaresis, but increased U-NaEx 24 only in normonatremic responders, which explains the scarcity of hypernatremia. Epithelial Na-channels in the distal nephrons, whose repression by TLV increases urinary sodium excretion, may be attenuated by reduced ATP-supply in worse hemodynamics under hyponatremia. (Int Heart J 2014; 55: 131-137) Key words: Heart failure, Vasopressin, Urine osmolality T he orally active vasopressin antagonists vaptans provide potential effects to treat chronic water-retaining disorders. 1) Among them, the vasopressin type 2 (V2) receptor antagonist tolvaptan (TLV) has been available for patients with heart failure (HF) with symptomatic congestion or hyponatremia.2) TLV has been demonstrated to ameliorate congestion, stabilize hemodynamics, and improve renal function without any signifi cant adverse effects.3-7) We also reported the effi cacy and safety of TLV in (1) amelioration of congestion even in stage D HF patients and (2) improvement of renal function by converting ongoing diuretics to TLV. 8,9) With respect to serum sodium concentration (S-Na), various studies in Europe and the United States have demonstrated the effi cacy of TLV to improve hyponatremia with little chance of hypernatremia, ie, S-Na > 145 mEq/L (eg, 1.7% of hypernatremia in the EVEREST study and 0% in the QUEST study). 2,6,[10][11][12] In Japan, we can administer TLV to HF patients to treat their congestion regardless of baseline S-Na as long as hypernatremia or rapid increases in S-Na do not develop. However, no studies have examined the effi cacy and safety of TLV in patients with normonatremia thus far. Therefore, we have analyzed and compared the effect of TLV on S-Na between patients with and witho...

Tolvaptan for hyponatremia with preserved sodium pool in critically ill patients

“…To better elucidate the potential mechanisms, and to possibly provide clinicians with predictors of the response to Tolvaptan, we searched for variables associated to the degree of the effect. As already reported [ 23 , 33 , 45 ], baseline [Na + ] was negatively associated with the subsequent rise in [Na + ] resulting from treatment, i.e., the lower the baseline [Na + ], the bigger the response. This could merely reflect the fact that subjects with higher baseline [Na + ] have less room for improvement, and likely reflect a lower degree of AVP activation.…”

“…Vaptans are a recently introduced class of vasopressin V2-receptor antagonists, yielding to an increased electrolyte-free water excretion and, thus, increased serum sodium concentration [ 22 ]. Several studies showed their safety and effectiveness in hyponatremia with preserved total body sodium pool in different categories of patients [ 17 , 23 – 27 ]; however, the experience with these drugs is limited in the critical care setting. After positive initial experience with oral Tolvaptan in single cases [ 28 , 29 ], we sought to analyze our case series to investigate the short-term outcomes on water and electrolyte balance for patients prescribed oral vaptans for hyponatremia with preserved total body sodium pool within our ICU.…”

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan

“…The change in the Na level is correlated with the serum Na level prior to receiving tolvaptan ( 22 , 23 ). In 2016, Hirai et al evaluated the risk of hypernatremia; a baseline Na level of ≥140 mEq/L, initial tolvaptan ≥7.5 mg/day, and a serum BUN/Cr ratio of ≥20 were independent risk factors for early-onset hypernatremia, particularly in elderly patients ( 24 ).…”

Effects of tolvaptan on urine output in hospitalized heart failure patients with hypoalbuminemia or proteinuria

“…Two mechanisms of this efficacy could be considered. First, natriuretic effects of tolvaptan have been demonstrated via the decreases in sodium reabsorption against the effect of vasopressin with the activation of epithelial Na-channels in the distal nephron [ 32 , 33 ]. Second, tolvaptan restored reportedly podocyte injury in nephrotic rats [ 34 ], which had intraglomerular hypertension by podocyte injury via activation of vasopressin.…”