PMID- 21903984 OWN - NLM STAT- MEDLINE DCOM- 20120207 LR - 20220316 IS - 1555-905X (Electronic) IS - 1555-9041 (Print) IS - 1555-9041 (Linking) VI - 6 IP - 10 DP - 2011 Oct TI - Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. PG - 2499-507 LID - 10.2215/CJN.03530411 [doi] AB - BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD), a frequent cause of end-stage renal disease, has no cure. V2-specific vasopressin receptor antagonists delay disease progression in animal models. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This is a prospectively designed analysis of annual total kidney volume (TKV) and thrice annual estimated GFR (eGFR) measurements, from two 3-year studies of tolvaptan in 63 ADPKD subjects randomly matched 1:2 to historical controls by gender, hypertension, age, and baseline TKV or eGFR. Prespecified end points were group differences in log-TKV (primary) and eGFR (secondary) slopes for month 36 completers, using linear mixed model (LMM) analysis. Sensitivity analyses of primary and secondary end points included LMM using all subject data and mixed model repeated measures (MMRM) of change from baseline at each year. Pearson correlation tested the association between log-TKV and eGFR changes. RESULTS: Fifty-one subjects (81%) completed 3 years of tolvaptan therapy; all experienced adverse events (AEs), with AEs accounting for six of 12 withdrawals. Baseline TKV (controls 1422, tolvaptan 1635 ml) and eGFR (both 62 ml/min per 1.73 m(2)) were similar. Control TKV increased 5.8% versus 1.7%/yr for tolvaptan (P < 0.001, estimated ratio of geometric mean 0.96 [95% confidence interval 0.95 to 0.97]). Corresponding annualized eGFR declined: -2.1 versus -0.71 ml/min per 1.73 m(2)/yr (P = 0.01, LMM group difference 1.1 ml/min per 1.73 m(2)/yr [95% confidence interval 0.24 to 1.9]). Sensitivity analyses including withdrawn subjects were similar, whereas MMRM analyses were significant at each year for TKV and nonsignificant for eGFR. Increasing TKV correlated with decreasing eGFR (r = -0.21, P < 0.01). CONCLUSION: ADPKD cyst growth progresses more slowly with tolvaptan than in historical controls, but AEs are common. FAU - Higashihara, Eiji AU - Higashihara E AD - Kyorin University School of Medicine, Mitaka, Tokyo, Japan. FAU - Torres, Vicente E AU - Torres VE FAU - Chapman, Arlene B AU - Chapman AB FAU - Grantham, Jared J AU - Grantham JJ FAU - Bae, Kyongtae AU - Bae K FAU - Watnick, Terry J AU - Watnick TJ FAU - Horie, Shigeo AU - Horie S FAU - Nutahara, Kikuo AU - Nutahara K FAU - Ouyang, John AU - Ouyang J FAU - Krasa, Holly B AU - Krasa HB FAU - Czerwiec, Frank S AU - Czerwiec FS CN - TEMPOFormula and 156-05-002 Study Investigators LA - eng SI - ClinicalTrials.gov/NCT00413777 SI - ClinicalTrials.gov/NCT00841568 PT - Controlled Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20110908 PL - United States TA - Clin J Am Soc Nephrol JT - Clinical journal of the American Society of Nephrology : CJASN JID - 101271570 RN - 0 (Antidiuretic Hormone Receptor Antagonists) RN - 0 (Benzazepines) RN - 0 (Hormone Antagonists) RN - 21G72T1950 (Tolvaptan) SB - IM MH - Adolescent MH - Adult MH - *Antidiuretic Hormone Receptor Antagonists MH - Benzazepines/adverse effects/*therapeutic use MH - Disease Progression MH - Female MH - Glomerular Filtration Rate/drug effects MH - Hormone Antagonists/adverse effects/*therapeutic use MH - Humans MH - Japan MH - Kidney/*drug effects/pathology/physiopathology MH - Male MH - Middle Aged MH - North America MH - Polycystic Kidney, Autosomal Dominant/*drug therapy/pathology/physiopathology MH - Prospective Studies MH - Time Factors MH - Tolvaptan MH - Treatment Outcome MH - Young Adult PMC - PMC3359559 FIR - Hishida, Akira IR - Hishida A FIR - Gejyo, Fumitake IR - Gejyo F FIR - Nitatori, Toshiaki IR - Nitatori T FIR - Goldstein, Sidney IR - Goldstein S FIR - Cowley, Benjamin IR - Cowley B FIR - Torra, Roser IR - Torra R FIR - Wei, Lee-Jen IR - Wei LJ FIR - School, Harvard IR - School H FIR - Sato, Osamu IR - Sato O FIR - Okada, Tadashi IR - Okada T FIR - Bennett, William IR - Bennett W FIR - Walczyk, Michael IR - Walczyk M FIR - Blumenfeld, Jon IR - Blumenfeld J FIR - Donahue, Stephanie IR - Donahue S FIR - Prince, Martin IR - Prince M FIR - Kline Bolton, W IR - Kline Bolton W FIR - Rosner, Mitchell IR - Rosner M FIR - Chapman, Arlene IR - Chapman A FIR - Rahbari-Oskoui, Frederick IR - Rahbari-Oskoui F FIR - Martin, Diego IR - Martin D FIR - Edelstein, Charles IR - Edelstein C FIR - Berl, Tomas IR - Berl T FIR - Cicerchi, Janis IR - Cicerchi J FIR - Burke, Brian L IR - Burke BL FIR - Koren, Michael IR - Koren M FIR - Greco, Susan N IR - Greco SN FIR - Jacqmein, Jeffry IR - Jacqmein J FIR - Bartilucci, Darlene IR - Bartilucci D FIR - Frisk, Mark IR - Frisk M FIR - Schulman, Gerald IR - Schulman G FIR - Lewis, Julia IR - Lewis J FIR - Golper, Thomas IR - Golper T FIR - Arildsen, Ronald IR - Arildsen R FIR - Swan, Suzanne IR - Swan S FIR - Cannon, Courtney IR - Cannon C FIR - Cunningham, James IR - Cunningham J FIR - Torres, Vicente IR - Torres V FIR - Hogan, Marie IR - Hogan M FIR - Fervenza, Fernando IR - Fervenza F FIR - Glockner, James IR - Glockner J FIR - Watnick, Terry IR - Watnick T FIR - Turban, Sharon IR - Turban S FIR - Macura, Katarzyna J IR - Macura KJ FIR - Winklhofer, Franz IR - Winklhofer F FIR - Bertsch, Judson IR - Bertsch J FIR - Wang, Connie IR - Wang C FIR - Wetzel, Louis IR - Wetzel L FIR - Iino, Yasuhiko IR - Iino Y FIR - Kamata, Kouju IR - Kamata K FIR - Sakamoto, Hisato IR - Sakamoto H FIR - Kamura, Koichi IR - Kamura K FIR - Kanno, Tatsuhiko IR - Kanno T FIR - Nakamoto, Hidetomo IR - Nakamoto H FIR - Ranzan, Musashi IR - Ranzan M FIR - Muto, Satoru IR - Muto S FIR - Yasuda, Mitsuko IR - Yasuda M FIR - Horie, Shigeo IR - Horie S FIR - Ide, Hisamitsu IR - Ide H FIR - Naya, Yukio IR - Naya Y FIR - Nihei, Naoki IR - Nihei N FIR - Araki, Kazuhiro IR - Araki K FIR - Nitta, Kosaku IR - Nitta K FIR - Tsuchiya, Ken IR - Tsuchiya K FIR - Arai, Junko IR - Arai J FIR - Okegawa, Takatsugu IR - Okegawa T FIR - Takaichi, Kenmei IR - Takaichi K FIR - Ubara, Yoshifumi IR - Ubara Y FIR - Tsukamoto, Yusuke IR - Tsukamoto Y FIR - Okado, Tomokazu IR - Okado T FIR - Kuwahara, Michio IR - Kuwahara M FIR - Ayata, Mikiko IR - Ayata M FIR - Takada, Shigeru IR - Takada S FIR - Inoshita, Seiji IR - Inoshita S FIR - Kuyama, Tamaki IR - Kuyama T FIR - Asai, Tomoki IR - Asai T EDAT- 2011/09/10 06:00 MHDA- 2012/02/09 06:00 PMCR- 2012/10/01 CRDT- 2011/09/10 06:00 PHST- 2011/09/10 06:00 [entrez] PHST- 2011/09/10 06:00 [pubmed] PHST- 2012/02/09 06:00 [medline] PHST- 2012/10/01 00:00 [pmc-release] AID - CJN.03530411 [pii] AID - 03530411 [pii] AID - 10.2215/CJN.03530411 [doi] PST - ppublish SO - Clin J Am Soc Nephrol. 2011 Oct;6(10):2499-507. doi: 10.2215/CJN.03530411. Epub 2011 Sep 8.