Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease
Open accessAbstract
BACKGROUND: -receptor antagonist tolvaptan slowed the growth in total kidney volume and the decline in the estimated glomerular filtration rate (GFR) but also caused more elevations in aminotransferase and bilirubin levels. The efficacy and safety of tolvaptan in patients with later-stage ADPKD are unknown. METHODS: were randomly assigned in a 1:1 ratio to receive tolvaptan or placebo for 12 months. The primary end point was the change in the estimated GFR from baseline to follow-up, with adjustment for the exact duration that each patient participated (interpolated to 1 year). Safety assessments were conducted monthly. RESULTS: ; 95% CI, 0.86 to 1.68; P<0.001). Elevations in the alanine aminotransferase level (to >3 times the upper limit of the normal range) occurred in 38 of 681 patients (5.6%) in the tolvaptan group and in 8 of 685 (1.2%) in the placebo group. Elevations in the aminotransferase level were reversible after stopping tolvaptan. No elevations in the bilirubin level of more than twice the upper limit of the normal range were detected. CONCLUSIONS: Tolvaptan resulted in a slower decline than placebo in the estimated GFR over a 1-year period in patients with later-stage ADPKD. (Funded by Otsuka Pharmaceuticals and Otsuka Pharmaceutical Development and Commercialization; REPRISE ClinicalTrials.gov number, NCT02160145 .).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Ciliopathies are associated with numerous neuropathologies, including anatomical abnormalities and neuropsychiatric disorders.
“ciliopathies are associated with numerous neuropathologies, including anatomical abnormalities and neuropsychiatric disorders 165.”
From Cellular signalling by primary cilia in development, organ function and disease (2019) · cites this paper as [165]
The Tolvaptan in Later-Stage ADPKD section describes kidney cyst development, and the Discussion addresses trial adverse events; neither addresses neuropathologies associated with ciliopathies. Searches for neuropsychiatric disorders, brain abnormalities, and related neurological terms found no passage supporting the claim. (LLM, conf=0.75)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A New Equation to Estimate Glomerular Filtration Rate
Levey, A. S., Stevens, L. A., Schmid, C. H., Zhang, Y. (., Castro, A. F., Feldman, H. I., Kusek, J. W., Eggers, P., Van Lente, F., Greene, T., et al. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-9-200905050-00006 · Cited by 25,603 · see citing works
Levey, A. S., Coresh, J., Greene, T., Stevens, L. A., Zhang, Y., Hendriksen, S. M., Kusek, J. W., & Lente, F. V. (2006) · Annals of Internal Medicine · doi:10.7326/0003-4819-145-4-200608150-00004 · Cited by 5,726 · see citing works
Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease
Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Grantham, J. J., Higashihara, E., Perrone, R. D., Krasa, H. B., Ouyang, J., & Czerwiec, F. S. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1205511 · Cited by 1,621 · see citing works
Self-citationUnified Criteria for Ultrasonographic Diagnosis of ADPKD
Pei, Y., Obaji, J., Dupuis, A., Paterson, A. D., Magistroni, R., Dicks, E. L., Parfrey, P. S., Cramer, B. C., Coto, E., Torrá, R., et al. (2008) · Journal of the American Society of Nephrology · doi:10.1681/asn.2008050507 · Cited by 764 · see citing works
Gattone, V. H., Wang, X., Harris, P. C., & Torres, V. E. (2003) · Nature Medicine · doi:10.1038/nm935 · Cited by 670 · see citing works
Self-citationImaging Classification of Autosomal Dominant Polycystic Kidney Disease
Irazabal, M. V., Rangel, L. J., Bergstralh, E. J., Osborn, S. L., Harmon, A. J., Sundsbak, J. L., Bae, K. T., Chapman, A. B., Grantham, J. J., Mrug, M. M., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013101138 · Cited by 628 · see citing works
Self-citationChapman, A. B., Devuyst, O., Eckardt, K., Gansevoort, R. T., Harris, T., Horie, S., Kasiske, B. L., Odland, D., Pei, Y., Perrone, R. D., et al. (2015) · Kidney International · doi:10.1038/ki.2015.59 · Cited by 614 · see citing works
Self-citationEffective treatment of an orthologous model of autosomal dominant polycystic kidney disease
Torres, V. E., Wang, X., Qian, Q., Somlo, S., Harris, P. C., & Gattone, V. H. (2004) · Nature Medicine · doi:10.1038/nm1004 · Cited by 480 · see citing works
Self-citationGall, É. C.-L., Audrézet, M., Rousseau, A., Hourmant, M., Renaudineau, E., Charasse, C., Morin, M.-P., Moal, M., Dantal, J., Wehbe, B., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015010016 · Cited by 359 · see citing works
Wang, X., Gattone, V. H., Harris, P. C., & Torres, V. E. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004121090 · Cited by 333 · see citing works
Self-citationCyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells
Belibi, F. A., Reif, G. A., Wallace, D. P., Yamaguchi, T., OLSEN, L. T., Li, H., Helmkamp, G. M., & Grantham, J. J. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00843.x · Cited by 295 · see citing works
Vasopressin Directly Regulates Cyst Growth in Polycystic Kidney Disease
Wang, X., Wu, Y., Ward, C. J., Harris, P. C., & Torres, V. E. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2007060688 · Cited by 289 · see citing works
Self-citationWhy kidneys fail in autosomal dominant polycystic kidney disease
Grantham, J. J., Mulamalla, S., & Swenson-Fields, K. I. (2011) · Nature Reviews Nephrology · doi:10.1038/nrneph.2011.109 · Cited by 287 · see citing works
Autosomal dominant polycystic kidney disease: the changing face of clinical management
Ong, A. C. M., Devuyst, O., Knebelmann, B., & Walz, G. (2015) · The Lancet · doi:10.1016/s0140-6736(15)60907-2 · Cited by 280 · see citing works
Self-citationIncreased Water Intake Decreases Progression of Polycystic Kidney Disease in the PCK Rat
Nagao, S., Nishii, K., Katsuyama, M., Kurahashi, H., Marunouchi, T., Takahashi, H., & Wallace, D. P. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006030251 · Cited by 240 · see citing works
Vasopressin: a novel target for the prevention and retardation of kidney disease?
Bankir, L., Bouby, N., & Ritz, E. (2013) · Nature Reviews Nephrology · doi:10.1038/nrneph.2013.22 · Cited by 214 · see citing works
Watkins, P. B., Lewis, J. H., Kaplowitz, N., Alpers, D., Blais, J. D., Smotzer, D. M., Krasa, H. B., Ouyang, J., Torres, V. E., Czerwiec, F. S., et al. (2015) · Drug Safety · doi:10.1007/s40264-015-0327-3 · Cited by 195 · see citing works
Self-citationAging and the Kidneys: Anatomy, Physiology and Consequences for Defining Chronic Kidney Disease
Glassock, R. J., & Rule, A. D. (2016) · The Nephron journals/Nephron journals · doi:10.1159/000445450 · Cited by 195 · see citing works
Torres, V. E., Chapman, A. B., Devuyst, O., et al. (2017) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfx043 · Cited by 185 · see citing works
Self-citationReif, G. A., Yamaguchi, T., Nivens, E., et al. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00243.2011 · Cited by 161 · see citing works
Torres, V. E., Higashihara, E., Devuyst, O., et al. (2016) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.06300615 · Cited by 152 · see citing works
Self-citationIrazabal, M. V., Torres, V. E., Hogan, M. C., Glockner, J. F., King, B. F., Ofstie, T. G., Krasa, H. B., Ouyang, J., & Czerwiec, F. S. (2011) · Kidney International · doi:10.1038/ki.2011.119 · Cited by 137 · see citing works
Self-citationTolvaptan plus Pasireotide Shows Enhanced Efficacy in a PKD1 Model
Hopp, K., Sieben, C. J., Wang, X., Ye, H., Harris, P. C., & Torres, V. E. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013121312 · Cited by 121 · see citing works
Self-citationPerrone, R. D., Mouksassi, S., Romero, K., et al. (2017) · Kidney International Reports · doi:10.1016/j.ekir.2017.01.003 · Cited by 118 · see citing works
Self-citationBoertien, W. E., Meijer, E., de Jong, P. E., Bakker, S. J. L., Czerwiec, F. S., Struck, J., Oberdhan, D., Shoaf, S. E., Krasa, H. B., & Gansevoort, R. T. (2013) · Kidney International · doi:10.1038/ki.2013.285 · Cited by 90 · see citing works
Self-citationDynamic patterns of gene expression in the developing pronephros of Xenopus laevis
Carroll, T. J., Wallingford, J. B., & Vize, P. D. (1999) · Developmental Genetics · doi:10.1002/(sici)1520-6408(1999)24:3/4 · Cited by 71 · see citing works
Aihara, M., Fujiki, H., Mizuguchi, H., et al. (2014) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.114.213256 · Cited by 66 · see citing works
Torres, V. E., Chapman, A. B., Devuyst, O., et al. (2017) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfx079 · Cited by 61 · see citing works
Self-citationVasopressin in chronic kidney disease: an elephant in the room?
Torres, V. E. (2009) · Kidney International · doi:10.1038/ki.2009.325 · Cited by 58 · see citing works
Self-citationEffects of hydration in rats and mice with polycystic kidney disease
Hopp, K., Wang, X., Ye, H., Irazabal, M. V., Harris, P. C., & Torres, V. E. (2014) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00345.2014 · Cited by 57 · see citing works
Self-citationDevuyst, O., Chapman, A. B., Shoaf, S. E., et al. (2017) · Kidney International Reports · doi:10.1016/j.ekir.2017.07.004 · Cited by 57 · see citing works
Self-citationEffects of exogenous desmopressin on a model of heat stress nephropathy in mice
Roncal-Jiménez, C. A., Milagres, T., Andrés-Hernando, A., Kuwabara, M., Jensen, T., Song, Z., Bjornstad, P., García, G., Sato, Y., Sánchez‐Lozada, L. G., et al. (2016) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00495.2016 · Cited by 42 · see citing works
Torres, V. E., Devuyst, O., Chapman, A. B., et al. (2017) · American Journal of Nephrology · doi:10.1159/000456087 · Cited by 27 · see citing works
Self-citationPerrone, R. D., Mouksassi, S., Romero, K., et al. (2017) · Kidney International Reports · doi:10.1016/j.ekir.2017.02.011 · Cited by 22 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [9]9. Gattone VH II, Maser RL, Tian C, Rosenberg JM, Branden MG. Develop- mental expression of urine concentration- associated genes and their altered expres- sion in murine infantile-type polycystic kidney disease. Dev Genet 1999; 24: 309- 18.
Cited by
Sorted by citations
Cellular signalling by primary cilia in development, organ function and disease
Anvarian, Z., Mykytyn, K., Mukhopadhyay, S., Pedersen, L. B., & Christensen, S. T. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0116-9 · Cited by 845 · see citing works
Autosomal dominant polycystic kidney disease
Cornec-Le Gall, E., Alam, A., & Perrone, R. D. (2019) · The Lancet · doi:10.1016/s0140-6736(18)32782-x · Cited by 624 · see citing works
Self-citation
- Authors
- Torres, V. E., Chapman, A. B., Devuyst, O., Gansevoort, R. T., Perrone, R. D., Koch, G., Ouyang, J., McQuade, R. D., Blais, J. D., Czerwiec, F. S., & Sergeyeva, O.
- Affiliations
- Tufts Medical Center (US)
- University of North Carolina at Chapel Hill (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2017-11-16
- Volume
- 377
- Issue
- 20
- Pages
- 1930-1942
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2765795120
- Cited by
- 639
- References
- 34
- Citations by year
- 2026: 69 · 2025: 71 · 2024: 69 · 2023: 69 · 2022: 73 · 2021: 82 · 2020: 99 · 2019: 61 · 2018: 44 · 2017: 1
- FWCI
- 37.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- New England Journal of Medicine (publishedVersion, other-oa)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- DIAL (Catholic University of Leuven) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
- UCL Discovery (University College London) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- U.S. Department of Veterans Affairs (I01-BX002298)
- PKD Foundation
- Polycystic Kidney Disease Charity
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK074038, R01DK097423)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Physiology › Tuberous Sclerosis Complex Research
- Keywords
- tolvaptan, autosomal dominant polycystic kidney disease, renin-angiotensin system inhibitors, estimated glomerular filtration rate decline, kidney volume, aminotransferase elevation, drug safety
- MeSH terms
- Tolvaptan, Adolescent, Adult, Aged, Alanine Transaminase, Benzazepines, Bilirubin, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Kidney Failure, Chronic, Male, Middle Aged, Polycystic Kidney, Autosomal Dominant, Young Adult, Antidiuretic Hormone Receptor Antagonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
