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Erschienen in: Clinical and Experimental Nephrology 3/2018

01.06.2018 | Original article

Tolvaptan promotes urinary excretion of sodium and urea: a retrospective cohort study

verfasst von: Satoshi Minami, Takayuki Hamano, Hirotsugu Iwatani, Masayuki Mizui, Yoshiki Kimura, Yoshitaka Isaka

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 3/2018

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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.
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Literatur
1.
Zurück zum Zitat Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367:2407–18.CrossRefPubMedPubMedCentral Torres VE, Chapman AB, Devuyst O, Gansevoort RT, Grantham JJ, Higashihara E, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367:2407–18.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Gattone VH 2nd, Wang X, Harris PC, Torres VE. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med. 2003;9:1323–6.CrossRefPubMed Gattone VH 2nd, Wang X, Harris PC, Torres VE. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nat Med. 2003;9:1323–6.CrossRefPubMed
3.
Zurück zum Zitat Wang X, Gattone V 2nd, Harris PC, Torres VE. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat. J Am Soc Nephrol. 2005;16:846–51.CrossRefPubMed Wang X, Gattone V 2nd, Harris PC, Torres VE. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat. J Am Soc Nephrol. 2005;16:846–51.CrossRefPubMed
4.
Zurück zum Zitat Perucca J, Bichet DG, Bardoux P, Bouby N, Bankir L. Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists. J Am Soc Nephrol. 2008;19:1721–31.CrossRefPubMedPubMedCentral Perucca J, Bichet DG, Bardoux P, Bouby N, Bankir L. Sodium excretion in response to vasopressin and selective vasopressin receptor antagonists. J Am Soc Nephrol. 2008;19:1721–31.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Ecelbarger CA, Kim GH, Terris J, Masilamani S, Mitchell C, Reyes I, et al. Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney. Am J Physiol Renal Physiol. 2000;279:F46–53.CrossRefPubMed Ecelbarger CA, Kim GH, Terris J, Masilamani S, Mitchell C, Reyes I, et al. Vasopressin-mediated regulation of epithelial sodium channel abundance in rat kidney. Am J Physiol Renal Physiol. 2000;279:F46–53.CrossRefPubMed
6.
Zurück zum Zitat Sun A, Grossman EB, Lombardi M, Hebert SC. Vasopressin alters the mechanism of apical Cl− entry from Na+:Cl− to Na+:K+:2Cl− cotransport in mouse medullary thick ascending limb. J Membr Biol. 1991;120:83–94.CrossRefPubMed Sun A, Grossman EB, Lombardi M, Hebert SC. Vasopressin alters the mechanism of apical Cl entry from Na+:Cl to Na+:K+:2Cl cotransport in mouse medullary thick ascending limb. J Membr Biol. 1991;120:83–94.CrossRefPubMed
7.
Zurück zum Zitat Bankir LT, Trinh-Trang-Tan MM. Renal urea transporters Direct and indirect regulation by vasopressin. Exp Physiol. 2000;85:243s–52s.CrossRefPubMed Bankir LT, Trinh-Trang-Tan MM. Renal urea transporters Direct and indirect regulation by vasopressin. Exp Physiol. 2000;85:243s–52s.CrossRefPubMed
8.
Zurück zum Zitat Kim SR, Hasunuma T, Sato O, Okada T, Kondo M, Azuma J. Pharmacokinetics, pharmacodynamics and safety of tolvaptan, a novel, oral, selective nonpeptide AVP V2-receptor antagonist: results of single- and multiple-dose studies in healthy Japanese male volunteers. Cardiovasc Drugs Ther. 2011;25(Suppl 1):S5–17.CrossRefPubMed Kim SR, Hasunuma T, Sato O, Okada T, Kondo M, Azuma J. Pharmacokinetics, pharmacodynamics and safety of tolvaptan, a novel, oral, selective nonpeptide AVP V2-receptor antagonist: results of single- and multiple-dose studies in healthy Japanese male volunteers. Cardiovasc Drugs Ther. 2011;25(Suppl 1):S5–17.CrossRefPubMed
9.
Zurück zum Zitat Kajimoto K, Abe T. Blood urea nitrogen as a marker of the acute response to addition of tolvaptan to standard therapy in patients hospitalized for acute heart failure syndromes. Int J Cardiol. 2014;177:589–91.CrossRefPubMed Kajimoto K, Abe T. Blood urea nitrogen as a marker of the acute response to addition of tolvaptan to standard therapy in patients hospitalized for acute heart failure syndromes. Int J Cardiol. 2014;177:589–91.CrossRefPubMed
11.
Zurück zum Zitat Konstam MA, Gheorghiade M, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297:1319–31.CrossRefPubMed Konstam MA, Gheorghiade M, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297:1319–31.CrossRefPubMed
12.
Zurück zum Zitat Matsuzaki M, Hori M, Izumi T, Fukunami M, Tolvaptan I. Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study). Cardiovasc Drugs Ther. 2011;25(Suppl 1):S33–45.CrossRefPubMed Matsuzaki M, Hori M, Izumi T, Fukunami M, Tolvaptan I. Efficacy and safety of tolvaptan in heart failure patients with volume overload despite the standard treatment with conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study). Cardiovasc Drugs Ther. 2011;25(Suppl 1):S33–45.CrossRefPubMed
13.
Zurück zum Zitat Imamura T, Kinugawa K, Shiga T, Kato N, Muraoka H, Minatsuki S, et al. Novel criteria of urine osmolality effectively predict response to tolvaptan in decompensated heart failure patients. Circ J. 2013;77:397–404.CrossRefPubMed Imamura T, Kinugawa K, Shiga T, Kato N, Muraoka H, Minatsuki S, et al. Novel criteria of urine osmolality effectively predict response to tolvaptan in decompensated heart failure patients. Circ J. 2013;77:397–404.CrossRefPubMed
14.
Zurück zum Zitat Nishizawa Y, Nakamura T, Ohta H, Kushida K, Gorai I, Shiraki M, et al. Guidelines for the use of biochemical markers of bone turnover in osteoporosis (2004). J Bone Miner Metab. 2005;23:97–104.CrossRefPubMed Nishizawa Y, Nakamura T, Ohta H, Kushida K, Gorai I, Shiraki M, et al. Guidelines for the use of biochemical markers of bone turnover in osteoporosis (2004). J Bone Miner Metab. 2005;23:97–104.CrossRefPubMed
15.
Zurück zum Zitat von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.CrossRef von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007;147:573–7.CrossRef
16.
Zurück zum Zitat Japanese Society of Nephrology. Evidence-based Clinical Practice Guideline for CKD 2013. Clin Exp Nephrol. 2014;18:346–423.CrossRef Japanese Society of Nephrology. Evidence-based Clinical Practice Guideline for CKD 2013. Clin Exp Nephrol. 2014;18:346–423.CrossRef
17.
Zurück zum Zitat Mori T, Oba I, Koizumi K, Kodama M, Shimanuki M, Tanno M, et al. Beneficial role of tolvaptan in the control of body fluids without reductions in residual renal function in patients undergoing peritoneal dialysis. Adv Perit Dial. 2013;29:33–7.PubMed Mori T, Oba I, Koizumi K, Kodama M, Shimanuki M, Tanno M, et al. Beneficial role of tolvaptan in the control of body fluids without reductions in residual renal function in patients undergoing peritoneal dialysis. Adv Perit Dial. 2013;29:33–7.PubMed
18.
Zurück zum Zitat Afsar B, Ortiz A, Covic A, Solak Y, Goldsmith D, Kanbay M. Focus on renal congestion in heart failure. Clin Kidney J. 2016;9:39–47.CrossRefPubMed Afsar B, Ortiz A, Covic A, Solak Y, Goldsmith D, Kanbay M. Focus on renal congestion in heart failure. Clin Kidney J. 2016;9:39–47.CrossRefPubMed
19.
Zurück zum Zitat Schrier RW. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2009;20:1888–93.CrossRefPubMed Schrier RW. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2009;20:1888–93.CrossRefPubMed
20.
Zurück zum Zitat Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, et al. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014;371:2255–66.CrossRefPubMedPubMedCentral Schrier RW, Abebe KZ, Perrone RD, Torres VE, Braun WE, Steinman TI, et al. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med. 2014;371:2255–66.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann Intern Med. 2005;142:342–51.CrossRefPubMed Sarnak MJ, Greene T, Wang X, Beck G, Kusek JW, Collins AJ, et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann Intern Med. 2005;142:342–51.CrossRefPubMed
22.
Zurück zum Zitat Rinkel GJ. Natural history, epidemiology and screening of unruptured intracranial aneurysms. J Neuroradiol. 2008;35:99–103.CrossRefPubMed Rinkel GJ. Natural history, epidemiology and screening of unruptured intracranial aneurysms. J Neuroradiol. 2008;35:99–103.CrossRefPubMed
23.
Zurück zum Zitat Yang B, Bankir L. Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol. 2005;288:F881–96.CrossRefPubMed Yang B, Bankir L. Urea and urine concentrating ability: new insights from studies in mice. Am J Physiol Renal Physiol. 2005;288:F881–96.CrossRefPubMed
24.
Zurück zum Zitat Fenton RA, Flynn A, Shodeinde A, Smith CP, Schnermann J, Knepper MA. Renal phenotype of UT-A urea transporter knockout mice. J Am Soc Nephrol. 2005;16:1583–92.CrossRefPubMedPubMedCentral Fenton RA, Flynn A, Shodeinde A, Smith CP, Schnermann J, Knepper MA. Renal phenotype of UT-A urea transporter knockout mice. J Am Soc Nephrol. 2005;16:1583–92.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Gheorghiade M, Konstam MA, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297:1332–43.CrossRefPubMed Gheorghiade M, Konstam MA, Burnett JC, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297:1332–43.CrossRefPubMed
26.
Zurück zum Zitat Koeth RA, Kalantar-Zadeh K, Wang Z, Fu X, Tang WH, Hazen SL. Protein carbamylation predicts mortality in ESRD. J Am Soc Nephrol. 2013;24:853–61.CrossRefPubMedPubMedCentral Koeth RA, Kalantar-Zadeh K, Wang Z, Fu X, Tang WH, Hazen SL. Protein carbamylation predicts mortality in ESRD. J Am Soc Nephrol. 2013;24:853–61.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Drechsler C, Kalim S, Wenger JB, Suntharalingam P, Hod T, Thadhani RI, et al. Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease. Kidney Int. 2015;87:1201–8.CrossRefPubMedPubMedCentral Drechsler C, Kalim S, Wenger JB, Suntharalingam P, Hod T, Thadhani RI, et al. Protein carbamylation is associated with heart failure and mortality in diabetic patients with end-stage renal disease. Kidney Int. 2015;87:1201–8.CrossRefPubMedPubMedCentral
28.
Zurück zum Zitat Kalim S, Karumanchi SA, Thadhani RI, Berg AH. Protein carbamylation in kidney disease: pathogenesis and clinical implications. Am J Kidney Dis. 2014;64:793–803.CrossRefPubMedPubMedCentral Kalim S, Karumanchi SA, Thadhani RI, Berg AH. Protein carbamylation in kidney disease: pathogenesis and clinical implications. Am J Kidney Dis. 2014;64:793–803.CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Pietrement C, Gorisse L, Jaisson S, Gillery P. Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD. PLoS One. 2013;8:e82506.CrossRefPubMedPubMedCentral Pietrement C, Gorisse L, Jaisson S, Gillery P. Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD. PLoS One. 2013;8:e82506.CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Fenton RA, Chou CL, Stewart GS, Smith CP, Knepper MA. Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct. Proc Natl Acad Sci USA. 2004;101:7469–74.CrossRefPubMedPubMedCentral Fenton RA, Chou CL, Stewart GS, Smith CP, Knepper MA. Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct. Proc Natl Acad Sci USA. 2004;101:7469–74.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Li F, Lei T, Zhu J, Wang W, Sun Y, Chen J, et al. A novel small-molecule thienoquinolin urea transporter inhibitor acts as a potential diuretic. Kidney Int. 2013;83:1076–86.CrossRefPubMed Li F, Lei T, Zhu J, Wang W, Sun Y, Chen J, et al. A novel small-molecule thienoquinolin urea transporter inhibitor acts as a potential diuretic. Kidney Int. 2013;83:1076–86.CrossRefPubMed
Metadaten
Titel
Tolvaptan promotes urinary excretion of sodium and urea: a retrospective cohort study
verfasst von
Satoshi Minami
Takayuki Hamano
Hirotsugu Iwatani
Masayuki Mizui
Yoshiki Kimura
Yoshitaka Isaka
Publikationsdatum
01.06.2018
Verlag
Springer Singapore
Erschienen in
Clinical and Experimental Nephrology / Ausgabe 3/2018
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-017-1475-9

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