Satoshi Minami1, Takayuki Hamano2, Hirotsugu Iwatani3, Masayuki Mizui1, Yoshiki Kimura1, Yoshitaka Isaka1. 1. Department of Nephrology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. 2. Department of Comprehensive Kidney Disease Research, Osaka University Graduate School of Medicine, D11, 2-2 Yamadaoka, Suita, Osaka, Japan, 565-0871. hamatea@kid.med.osaka-u.ac.jp. 3. Department of Nephrology, National Hospital Organization Osaka National Hospital, Chuo-ku, Osaka, Osaka, Japan.
Abstract
BACKGROUND: Tolvaptan (TLV) promotes aquaresis; however, little is known about its effect on solute excretion in chronic kidney disease (CKD). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND:Tolvaptan (TLV) promotes aquaresis; however, little is known about its effect on solute excretion in chronic kidney disease (CKD). METHODS: We retrospectively studied CKDpatients 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 ureanitrogen (FeUN), and blood ureanitrogen (BUN) were monitored. RESULTS: 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 ADPKDpatients, 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. CONCLUSION: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.
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