Evidence map›Paper›PMID 26681730›Full record

Trial reportNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2016

Albuminuria and tolvaptan in autosomal-dominant polycystic kidney disease: results of the TEMPO 3:4 Trial.

Ron T Gansevoort, Esther Meijer, Arlene B Chapman, Frank S Czerwiec, Olivier Devuyst, Jared J Grantham, Eiji Higashihara, Holly B Krasa, John Ouyang, Ronald D Perrone and 2 more

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 3 pooled it
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.

  1. Pooled it
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  5. Trial
  6. Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2018
    Trial
  7. Bosutinib versus Placebo for Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2017
    Trial
  8. Article
  9. SGLT2 inhibition for patients with ADPKD - closing the evidence gap.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
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  16. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Ron T GansevoortDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Esther MeijerDivision of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Arlene B ChapmanDivision of Nephrology, Emory University School of Medicine, 201 Dowman Drive, Atlanta, Ga. 30322, US.
Frank S CzerwiecOtsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD 20850 USA.
Olivier DevuystDivision of Nephrology, Cliniques Universitaires St. Luc, Université Catholique de Louvain Medical School, 10 Avenue Hippocrate 1200, Brussels, Belgium.
Jared J GranthamKidney Institute and the Department of Internal Medicine, Kansas University Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160 Kansas City, KS, USA.
Eiji HigashiharaDepartment of Urology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo. 181-8611 Japan.
Holly B KrasaOtsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD 20850 USA.
John OuyangOtsuka Pharmaceutical Development and Commercialization, Inc., Rockville, MD 20850 USA.
Ronald D PerroneDepartment of Medicine, Division of Nephrology, TuftsMedical Center, Tufts University School of Medicine, 800 Washington St # 400, Boston, MA 02111, USA.
Vicente E TorresDivision of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, 200 First St. SW Rochester, MN 55905, USA.
TEMPO 3:4 Investigators
University of Groningen · NLAID Atlanta · USKaw Nation · USMayo Clinic · USMitaka Kohki (Japan) · JP

Funding

Pilot and FeasibilityP30DK090728 · NIDDK · MAYO CLINIC ROCHESTER · PI ROMERO, MICHAEL F. · 2010 to 2019
$11.8M
RENIN ANGIOTENSIN SYSTEM IN THE PATHOGENESIS OF ADPKDR01DK044863 · NIDDK · MAYO CLINIC ROCHESTER · PI TORRES, VICENTE E · 1991 to 2019
$4.5M
NIDDK NIH HHS P30 DK090728NIDDK NIH HHS R01 DK044863
6 · The paper itself

Abstract

backgroundThe TEMPO 3:4 Trial results suggested that tolvaptan had no effect compared with placebo on albuminuria in autosomal-dominant polycystic kidney disease (ADPKD) patients. However, the use of categorical 'albuminuria events' may have resulted in a loss of sensitivity to detect changes. The aim of this study is to investigate the effects of tolvaptan on albuminuria as a continuous variable.

methodsPost hoc analysis of a 3-year prospective, blinded randomized controlled trial, including 1375 ADPKD patients. Albuminuria was measured in a spot morning urine sample prior to tolvaptan dosing and expressed as albumin-to-creatinine ratio (ACR).

resultsBaseline median (interquartile range) ACR was 3.2 (1.7-7.1) mg/mmol. Of note, 47.9% of ADPKD patients had normal, 48.7% moderately increased and 3.4% severely increased ACR. Subjects with higher baseline ACR had higher blood pressure and total kidney volume (TKV) and lower estimated glomerular filtration rate (eGFR). During follow-up, higher baseline ACR was associated with more rapid eGFR loss (P < 0.0001 for trend), but not with rate of growth in TKV. During the 3-year trial, ACR rose in placebo- and decreased in tolvaptan-treated patients (+0.23 versus -0.40 mg/mmol). The difference ACR increased over time, reaching a maximum of 24% at Month 36 (P < 0.001). At that time only a minor difference in blood pressure was observed (mean arterial pressure -1.9 mmHg for tolvaptan). The decrease in ACR was similar in all subgroups investigated, and remained after withdrawal of study drug. The beneficial effect of tolvaptan on TKV growth and eGFR loss was stronger in patients with higher baseline ACR.

conclusionsIn ADPKD, higher baseline albuminuria was associated with more eGFR loss. Tolvaptan decreased albuminuria compared with placebo, independent of blood pressure. Treatment efficacy of tolvaptan on changes in TKV and eGFR was more readily detected in patients with higher albuminuria.

Indexed as

AgedAlbuminuriaAntidiuretic Hormone Receptor AntagonistsBenzazepinesDose-Response Relationship, DrugDouble-Blind MethodFemaleGlomerular Filtration RateHumansMaleMiddle AgedPolycystic Kidney, Autosomal DominantProspective StudiesTolvaptanTreatment OutcomeAntidiuretic Hormone Receptor AntagonistsBenzazepinesTolvaptanADPKDalbuminuriachronic renal failureeGFRvasopressin

Identifiers

PMID26681730
PMCPMC6367945
OpenAlexW2318270239

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.