Trial reportThe New England journal of medicine2017
Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease.
Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
In one paragraph
Trial report in The New England journal of medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02160145 (A Phase 3b, Multi-center, Randomized-withdrawal, Placebo-controlled, Double-blind, Parallel-group Trial to Compare the Efficacy and Safety of Tolvaptan), which is not on this map. Cited by 370 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
370citing papers in PubMed, 3 pooled it
45.6field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 3b, Multi-center, Randomized-withdrawal, Placebo-controlled, Double-blind, Parallel-group Trial to Compare the Efficacy and Safety of Tolvaptan (45 to 120 mg/Day, Split-dose) in Subjects With Chronic Kidney Disease Between Late Stage 2 to Early Stage 4 Due to Autosomal Dominant Polycystic Kidney Disease
Who cites it
370 citing papers in PubMed, 3 syntheses or guidelines pooled it, 592 citations in OpenAlex.
- Impact of polycystic kidney disease on outcomes after renal transplantation: systematic review and meta-analysis.Renal failure · 2025Pooled it
- Interventions for preventing the progression of autosomal dominant polycystic kidney disease.The Cochrane database of systematic reviews · 2024Pooled it
- Efficacy and safety of tolvaptan versus placebo in the treatment of patients with autosomal dominant polycystic kidney disease: a meta-analysis.International urology and nephrology · 2023Pooled it
- Tolvaptan for hyponatremia in patients with cirrhosis: a post hoc subgroup analysis of a multicenter, randomized, double-blind, placebo-controlled trial.Hepatology international · 2026Trial
- Tolvaptan pharmacokinetics and pharmacodynamics in adolescents with autosomal dominant polycystic kidney disease.European journal of pediatrics · 2025Trial
- Change in kidney volume growth rate and renal outcomes of tolvaptan treatment in autosomal dominant polycystic kidney disease: post-hoc analysis of TEMPO 3:4 trial.Clinical and experimental nephrology · 2025Trial
- Effects of salt and protein intake on polyuria in V2RA-treated ADPKD patients.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Trial
- Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial.Cell reports. Medicine · 2023Trial
- Tolvaptan for Children and Adolescents with Autosomal Dominant Polycystic Kidney Disease: Randomized Controlled Trial.Clinical journal of the American Society of Nephrology : CJASN · 2023Trial
- Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial.Clinical journal of the American Society of Nephrology : CJASN · 2022Trial
- The effect of tolvaptan on total kidney volume and inflammatory markers in autosomal dominant polycystic kidney disease.Clinical and experimental nephrology · 2026Article
- Unmasking Early Hepatorenal Fibrosis in Polycystic Kidney Disease Using Noninvasive Precision Molecular MRI of Collagen.bioRxiv : the preprint server for biology · 2026Article
- From mechanisms to clinical practice: a review of diuretic therapy in pediatric nephrology.Pediatric nephrology (Berlin, Germany) · 2026Review
- Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging Therapeutic Roles.Cardiovascular drugs and therapy · 2026Review
- PKD1 upstream open reading frames affect Polycystin-1 expression and polycystic kidney disease phenotypes.The Journal of clinical investigation · 2026Article
- Baseline hematuria in autosomal dominant polycystic kidney disease.Clinical kidney journal · 2026Article
- Association Between Tolvaptan Exposure and Venous Thromboembolism Risk in ADPKD: A Real-World Propensity-Matched EHR Study.Nephrology (Carlton, Vic.) · 2026Article
- Kidney Cyst Epithelia in Tuberous Sclerosis Complex (TSC) Exhibit Propagation and Expansion of A-Intercalated, but Loss of B-Intercalated and Principal Cells: The Role of FOXI1, FOXP1, and DMRT2 Transcription Factors.International journal of molecular sciences · 2026Article
- Comment on Yamazaki et al. Long-Term Effects of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Predictors of Treatment Response and Safety over 6 Years of Continuous Therapy.International journal of molecular sciences · 2026Article
- SGLT2 inhibitors in autosomal dominant polycystic kidney disease: rationale, evidence gaps, and ongoing clinical trials.International urology and nephrology · 2026Review
310 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 4 countries.
Vicente E TorresFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Arlene B ChapmanFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Olivier DevuystFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Ron T GansevoortFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Ronald D PerroneFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Gary KochFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
John OuyangFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Robert D McQuadeFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Jaime D BlaisFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Frank S CzerwiecFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
Olga SergeyevaFrom the Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN (V.E.T.); the Section of Nephrology, University of Chicago, Chicago (A.B.C.); the Institute of Physiology, University of Zurich, Zurich, Switzerland (O.D.); the Division of Nephrology, Université Catholique de Louvain Medical School, Brussels (O.D.); the Division of Nephrology, University Medical Center Groningen, Groningen, the Netherlands (R.T.G.); the Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston (R.D.P.); the Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill (G.K.); and Otsuka Pharmaceutical Development and Commercialization, Rockville, MD (J.O., R.D.M., J.D.B., F.S.C., O.S.).
REPRISE Trial Investigators
Otsuka (United States) · USPharmaceutical Product Development (United States) · USMayo Clinic · USTufts Medical Center · USUCLouvain · BEUniversity Medical Center Groningen · NLUniversity of Chicago · USUniversity of North Carolina at Chapel Hill · US
Funding
UAB Recessive PKD Research and Translational Core CenterP30DK074038 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI YODER, BRADLEY K. · 2005 to 2019
$16.6MRENIN ANGIOTENSIN SYSTEM IN THE PATHOGENESIS OF ADPKDR01DK044863 · NIDDK · MAYO CLINIC ROCHESTER · PI TORRES, VICENTE E · 1991 to 2019
$4.5MMechanisms of C3 effects in ARPKD pathogenesisR01DK097423 · NIDDK · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI MRUG, MICHAL · 2013 to 2017
$1.6MPathobiology of Complement C3 effects in ADPKDI01BX002298 · VA · BIRMINGHAM VA MEDICAL CENTER · PI MRUG, MICHAL · 2014 to 2017
–BLRD VA I01 BX002298NIDDK NIH HHS P30 DK074038NIDDK NIH HHS R01 DK097423
Abstract
backgroundIn a previous trial involving patients with early autosomal dominant polycystic kidney disease (ADPKD; estimated creatinine clearance, ≥60 ml per minute), the vasopressin V
methodsWe conducted a phase 3, randomized withdrawal, multicenter, placebo-controlled, double-blind trial. After an 8-week prerandomization period that included sequential placebo and tolvaptan run-in phases, during which each patient's ability to take tolvaptan without dose-limiting side effects was assessed, 1370 patients with ADPKD who were either 18 to 55 years of age with an estimated GFR of 25 to 65 ml per minute per 1.73 m
resultsThe change from baseline in the estimated GFR was -2.34 ml per minute per 1.73 m
conclusionsTolvaptan 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 .).
Indexed as
AdolescentAdultAgedAlanine TransaminaseAntidiuretic Hormone Receptor AntagonistsBenzazepinesBilirubinDouble-Blind MethodFemaleGlomerular Filtration RateHumansKidney Failure, ChronicMaleMiddle AgedPolycystic Kidney, Autosomal DominantTolvaptanAlanine TransaminaseAntidiuretic Hormone Receptor AntagonistsBenzazepinesBilirubinTolvaptan
Identifiers
What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
NCT02160145ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.