• Pajaree Krisanapan, Surachet Vongsanim, Pathomporn Pin-On, Chidchanok Ruengorn, and Kajohnsak Noppakun.
• Division of Nephrology, Department of Internal Medicine, Chiang Mai University, Chiang Mai, Thailand.
• Am. J. Kidney Dis. 2020 Aug 1; 76 (2): 203-212.

Rationale & ObjectiveFirst-line therapy for syndrome of inappropriate antidiuresis (SIAD) is fluid restriction. Additional treatment for patients who do not respond to fluid restriction are water restriction with furosemide or water restriction with furosemide and salt supplementation. However, the efficacy of these treatments has never been tested in a randomized controlled study. The objective of this study was to investigate whether, combined with fluid restriction, furosemide with or without sodium chloride (NaCl) supplementation was more effective than fluid restriction alone in the treatment of hyponatremia in SIAD.Study DesignOpen-label randomized controlled study.Setting & ParticipantsPatients with serum sodium concentrations ([Na+]) ≤ 130mmol/L due to SIAD.Intervention(S)Random assignment to 1 of 3 groups: fluid restriction alone (FR), fluid restriction and furosemide (FR+FM), or fluid restriction, furosemide, and NaCl (FR+FM+NaCl). Strictness of fluid restriction (<1,000 or<500mL/d) was guided by the urine to serum electrolyte ratio. Furosemide dosage was 20 to 40mg/d. NaCl supplements were 3g/d. All treatments were continued for 28 days.OutcomesThe primary outcome was change in [Na+] at days 4, 7, 14, and 28 after randomization.Results92 patients were recruited (FR, n=31; FR+FM, n=30; FR+FM+NaCl, n=31). Baseline [Na+] was 125±4mmol/L, and there were no significant differences between groups. Mean [Na+] on day 4 in all treatment groups was significantly increased from baseline by 5mmol/L (P<0.001); however, the change in [Na+] was not significantly different across groups (P=0.7). There was no significant difference in percentage of patients or time to reach [Na+] ≥ 130 or≥135mmol/L across the 3 groups. Acute kidney injury and hypokalemia (potassium≤3.0mmol/L) were more common in patients receiving furosemide.LimitationsOpen-label treatment.ConclusionsIn patients with SIAD, furosemide with NaCl supplement in combination with fluid restriction did not show benefits in correction of [Na+] compared with treatment with fluid restriction alone. Incidences of acute kidney injury and hypokalemia were increased in patients receiving furosemide.FundingNone.Trial RegistrationRegistered at the Thai Clinical Trial Registry with study number TCTR20170629004.Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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