Equivalent Efficacy and Decreased Rate of Overcorrection in Patients With Syndrome of Inappropriate Secretion of Antidiuretic Hormone Given Very Low-Dose Tolvaptan

Ramy M Hanna; Juan Carlos Velez; Anjay Rastogi; Minhtri K Nguyen; Mohammad K Kamgar; Kyaw Moe; Farid Arman; Huma Hasnain; Niloofar Nobakht; Umut Selamet; Ira Kurtz

doi:10.1016/j.xkme.2019.09.004

Equivalent Efficacy and Decreased Rate of Overcorrection in Patients With Syndrome of Inappropriate Secretion of Antidiuretic Hormone Given Very Low-Dose Tolvaptan

Kidney Med. 2019 Nov 26;2(1):20-28. doi: 10.1016/j.xkme.2019.09.004. eCollection 2020 Jan-Feb.

Authors

Ramy M Hanna^{1

2}, Juan Carlos Velez³, Anjay Rastogi¹, Minhtri K Nguyen¹, Mohammad K Kamgar¹, Kyaw Moe⁴, Farid Arman¹, Huma Hasnain¹, Niloofar Nobakht¹, Umut Selamet^{1

5}, Ira Kurtz⁶

Affiliations

¹ Division of Nephrology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
² Division of Nephrology, Department of Medicine, University of California Irvine School of Medicine, Irvine, CA.
³ Department of Nephrology, Ochsner School of Medicine, New Orleans, LA.
⁴ Lakewood Regional Medical Center, Lakewood, CA.
⁵ Division of Nephrology, Department of Medicine, Brigham Women's and Children's Hospital, Boston, MA.
⁶ Division of Nephrology, Department of Medicine, UCLA Brain Research Center, Los Angeles, CA.

Abstract

Rationale & objective: Euvolemic hyponatremia often occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Vasopressin 2 receptor antagonists may be used to treat SIADH. Several of the major trials used 15 mg of tolvaptan as the lowest effective dose in euvolemic and hypervolemic hyponatremia. However, a recent observational study suggested an elevated risk for serum sodium level overcorrection with 15 mg of tolvaptan in patients with SIADH.

Study design: A retrospective chart review study comparing outcomes in patients with SIADH treated with 15 versus 7.5 mg of tolvaptan.

Settings & participants: Patients with SIADH who were treated with a very low dose of tolvaptan (7.5 mg) at a single center compared with patients using a 15-mg dose from patient-level data from the observational study described previously.

Predictors: Tolvaptan dose of 7.5 versus 15 mg daily.

Outcomes: Appropriate response to tolvaptan, defined as an initial increase in serum sodium level > 3 mEq/L, and overcorrection of serum sodium level (>8 mEq/L per day, and >10 mEq/L per day in sensitivity analyses).

Analytical approach: Descriptive study with additional outcomes compared using t tests and F-tests (Fischer's Exact χ2 Test).

Results: Among 18 patients receiving 7.5 mg of tolvaptan, the mean rate of correction was 5.6 ± 3.1 mEq/L per day and 2 (11.1%) patients corrected their serum sodium levels by >8 mEq/L per day, with 1 of these increasing by >12 mEq/L per day. Of those receiving tolvaptan 7.5 mg, 14 had efficacy, with increases ≥ 3 mEq/L; similar results were seen with the 15-mg dose (21 of 28). There was a statistically significant higher chance of overcorrection with the use of 15 versus 7.5 mg of tolvaptan (11 of 28 vs 2 of 18; P = 0.05; and 10 of 28 vs 1 of 18; P = 0.03, for >8 mEq/L per day and >10 mEq/L per day, respectively).

Limitations: Small sample size, retrospective, and nonrandomized.

Conclusions: Tolvaptan, 7.5 mg, daily corrects hyponatremia with similar efficacy and less risk for overcorrection in patients with SIADH versus 15 mg of tolvaptan.

Keywords: SIADH; Tolvaptan; hyponatremia; osmotic demyelination syndrome.