Taro Akihisa1, Hiroshi Kataoka1, Shiho Makabe1, Shun Manabe1, Rie Yoshida1, Yusuke Ushio1, Masayo Sato1, Ken Tsuchiya2, Toshio Mochizuki3, Kosaku Nitta1. 1. Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 2. Department of Blood Purification, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. 3. Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. mtoshi@twmu.ac.jp.
Abstract
BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. METHODS: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The initial eGFR change was - 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. CONCLUSIONS: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.
BACKGROUND: Tolvaptan, a vasopressin V2 receptor antagonist, is used to treat autosomal-dominant polycystic kidney disease (ADPKD). Although tolvaptan curbs disease progression, a few reports have examined factors related to treatment response. The estimated glomerular filtration rate (eGFR) decreases soon after tolvaptan is initiated. We investigated whether initial eGFR decline affects renal prognosis of patients. METHODS: This was a single-center, retrospective observational cohort study. Eighty-three patients with ADPKD who initiated tolvaptan were selected. We analyzed the relationship of the initial eGFR change with clinical parameters and analyzed the annual eGFR change in terms of renal prognostic value using univariable and multivariable linear regression analyses. RESULTS: The initial eGFR change was - 4.6 ± 8.0%/month. The initial eGFR change correlated significantly with the annual eGFR change in multivariable analysis, suggesting that the larger decline in the initial eGFR change, the better the renal prognosis. Furthermore, the change in fractional excretion (FE) of free water (FEH2O) correlated positively with initial eGFR change. FEH2O and urea nitrogen FE (FEUN) increased significantly; however, sodium FE (FENa) level remained unchanged. In approximately half of the patients, FENa unexpectedly decreased. CONCLUSIONS: The initial eGFR decline might be caused by suppressing glomerular hyperfiltration, due to the pharmacological effect of tolvaptan, and/or by reducing renal plasma flow, due to potential volume depletion. The initial eGFR change reflects the tolvaptan effect, can be easily evaluated in clinical practice, and may be useful as one of the clinical indicator for predicting renal prognosis in patients under tolvaptan.
Authors: Wendy E Boertien; Esther Meijer; Paul E de Jong; Stephan J L Bakker; Frank S Czerwiec; Joachim Struck; Dorothee Oberdhan; Susan E Shoaf; Holly B Krasa; Ron T Gansevoort Journal: Kidney Int Date: 2013-07-31 Impact factor: 10.612
Authors: Maria V Irazabal; Vicente E Torres; Marie C Hogan; James Glockner; Bernard F King; Troy G Ofstie; Holly B Krasa; John Ouyang; Frank S Czerwiec Journal: Kidney Int Date: 2011-05-04 Impact factor: 10.612
Authors: Wendy E Boertien; Esther Meijer; Paul E de Jong; Gert J ter Horst; Remco J Renken; Eric J van der Jagt; Peter Kappert; John Ouyang; Gerwin E Engels; Willem van Oeveren; Joachim Struck; Frank S Czerwiec; Dorothee Oberdhan; Holly B Krasa; Ron T Gansevoort Journal: Am J Kidney Dis Date: 2015-01-15 Impact factor: 8.860
Authors: Vicente E Torres; Arlene B Chapman; Olivier Devuyst; Ron T Gansevoort; Jared J Grantham; Eiji Higashihara; Ronald D Perrone; Holly B Krasa; John Ouyang; Frank S Czerwiec Journal: N Engl J Med Date: 2012-11-03 Impact factor: 91.245
Authors: Vicente E Torres; Arlene B Chapman; Olivier Devuyst; Ron T Gansevoort; Ronald D Perrone; Gary Koch; John Ouyang; Robert D McQuade; Jaime D Blais; Frank S Czerwiec; Olga Sergeyeva Journal: N Engl J Med Date: 2017-11-04 Impact factor: 91.245
Authors: Fouad T Chebib; Ronald D Perrone; Arlene B Chapman; Neera K Dahl; Peter C Harris; Michal Mrug; Reem A Mustafa; Anjay Rastogi; Terry Watnick; Alan S L Yu; Vicente E Torres Journal: J Am Soc Nephrol Date: 2018-09-18 Impact factor: 10.121