Tolvaptan promotes urinary excretion of sodium and urea: a retrospective cohort study
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Tolvaptan (TLV) promotes aquaresis; however, little is known about its effect on solute excretion in chronic kidney disease (CKD).
We retrospectively studied CKD patients with decompensated heart failure (HF) or those with autosomal dominant polycystic kidney disease (ADPKD) receiving TLV. Patients with an increased urine volume of more than twice of daily variance were defined as “responders” in HF. We compared the ability of the urinary osmolality (U-OSM) change and urinary creatinine concentration ([U-Cr]) change to discriminate “responders”. The fractional excretion of sodium (FeNa) and urea nitrogen (FeUN), and blood urea nitrogen (BUN) were monitored.
In 30 responders among 53 HF patients, TLV increased FeUN significantly from 36.1 to 44.2% after starting TLV, but not FeNa. Since U-OSM is determined partially by urinary UN concentration, the decrease of [U-Cr] after treatment outperformed the U-OSM decrement to discriminate responders, as shown in receiver operating characteristic curve analysis and significantly higher net reclassification index. In 13 ADPKD patients, TLV increased FeUN (34.8, 47.3%, p = 0.02), and significant decrease of BUN by 2.3 (95% confidence interval 0.4–4.2) mg/dL was observed even 3 months after the intervention. Systolic blood pressure decreased significantly by 14.2 (95% confidence interval 4.0–24.4) mmHg along with the increase in FeNa, leading to reduced dosage of antihypertensives in 6 patients.
TLV promotes the excretion of sodium and urea. The change in [U-Cr] is useful for early discrimination of responders. Hypotension should be carefully monitored during high-dose TLV therapy.
KeywordsAutosomal dominant polycystic kidney disease Chronic kidney disease Decompensated heart failure Sodium excretion Tolvaptan Urea excretion
This study received no specific external funding.
Compliance with ethical standards
Conflict of interest
HI., T.H., and Y.I. have received grant support and lecture fees from Otsuka Pharmaceutical Company, which sells tolvaptan in Japan. The company played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; nor in the preparation, review, or approval of the manuscript.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number 16322) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
We provided all individual patients with the option to opt out of participation.
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