Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease

TEMPO 3:4 Investigators

Research output: Contribution to journalArticle

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Abstract

In the TEMPO 3:4 Trial, treatment with tolvaptan, a vasopressin V2 receptor antagonist, slowed the increase in total kidney volume and decline in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether plasma copeptin levels, a marker of plasma vasopressin, are associated with disease progression, and whether pre-treatment copeptin and treatment-induced change in copeptin are associated with tolvaptan treatment efficacy. This post hoc analysis included 1,280 TEMPO 3:4 participants (aged 18-50 years, estimated creatinine clearance ≥60 ml/min and total kidney volume ≥750 mL) who had plasma samples available at baseline for measurement of copeptin using an automated immunofluorescence assay. In placebo-treated subjects, baseline copeptin predicted kidney growth and eGFR decline over 3 years. These associations were independent of sex, age, and baseline eGFR, but were no longer statistically significant after additional adjustment for baseline total kidney volume. In tolvaptan-treated subjects, copeptin increased from baseline to week 3 (6.3 pmol/L versus 21.9 pmol/L, respectively). In tolvaptan-treated subjects with higher baseline copeptin levels, a larger treatment effect was noted with respect to kidney growth rate and eGFR decline. Tolvaptan-treated subjects with a larger percentage increase in copeptin from baseline to week 3 had a better disease outcome, with less kidney growth and eGFR decline after three years. Copeptin holds promise as a biomarker to predict outcome and tolvaptan treatment efficacy in ADPKD.

Original languageEnglish (US)
JournalKidney international
DOIs
StatePublished - Jan 1 2019

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Autosomal Dominant Polycystic Kidney
Disease Progression
Glomerular Filtration Rate
Kidney
Growth
tolvaptan
copeptins
Vasopressin Receptors
Therapeutics
Vasopressins
Fluorescent Antibody Technique
Creatinine
Biomarkers
Placebos

Keywords

  • ADPKD
  • AVP
  • copeptin
  • polycystic kidney disease
  • tolvaptan
  • vasopressin

ASJC Scopus subject areas

  • Nephrology

Cite this

Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease. / TEMPO 3:4 Investigators.

In: Kidney international, 01.01.2019.

Research output: Contribution to journalArticle

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abstract = "In the TEMPO 3:4 Trial, treatment with tolvaptan, a vasopressin V2 receptor antagonist, slowed the increase in total kidney volume and decline in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether plasma copeptin levels, a marker of plasma vasopressin, are associated with disease progression, and whether pre-treatment copeptin and treatment-induced change in copeptin are associated with tolvaptan treatment efficacy. This post hoc analysis included 1,280 TEMPO 3:4 participants (aged 18-50 years, estimated creatinine clearance ≥60 ml/min and total kidney volume ≥750 mL) who had plasma samples available at baseline for measurement of copeptin using an automated immunofluorescence assay. In placebo-treated subjects, baseline copeptin predicted kidney growth and eGFR decline over 3 years. These associations were independent of sex, age, and baseline eGFR, but were no longer statistically significant after additional adjustment for baseline total kidney volume. In tolvaptan-treated subjects, copeptin increased from baseline to week 3 (6.3 pmol/L versus 21.9 pmol/L, respectively). In tolvaptan-treated subjects with higher baseline copeptin levels, a larger treatment effect was noted with respect to kidney growth rate and eGFR decline. Tolvaptan-treated subjects with a larger percentage increase in copeptin from baseline to week 3 had a better disease outcome, with less kidney growth and eGFR decline after three years. Copeptin holds promise as a biomarker to predict outcome and tolvaptan treatment efficacy in ADPKD.",
keywords = "ADPKD, AVP, copeptin, polycystic kidney disease, tolvaptan, vasopressin",
author = "{TEMPO 3:4 Investigators} and Gansevoort, {Ron T.} and {van Gastel}, {Maatje D.A.} and Chapman, {Arlene B.} and Blais, {Jaime D.} and Czerwiec, {Frank S.} and Eiji Higashihara and Jennifer Lee and John Ouyang and Perrone, {Ronald D.} and Katrin Stade and Vicente Torres and Olivier Devuyst",
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AU - TEMPO 3:4 Investigators

AU - Gansevoort, Ron T.

AU - van Gastel, Maatje D.A.

AU - Chapman, Arlene B.

AU - Blais, Jaime D.

AU - Czerwiec, Frank S.

AU - Higashihara, Eiji

AU - Lee, Jennifer

AU - Ouyang, John

AU - Perrone, Ronald D.

AU - Stade, Katrin

AU - Torres, Vicente

AU - Devuyst, Olivier

PY - 2019/1/1

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N2 - In the TEMPO 3:4 Trial, treatment with tolvaptan, a vasopressin V2 receptor antagonist, slowed the increase in total kidney volume and decline in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether plasma copeptin levels, a marker of plasma vasopressin, are associated with disease progression, and whether pre-treatment copeptin and treatment-induced change in copeptin are associated with tolvaptan treatment efficacy. This post hoc analysis included 1,280 TEMPO 3:4 participants (aged 18-50 years, estimated creatinine clearance ≥60 ml/min and total kidney volume ≥750 mL) who had plasma samples available at baseline for measurement of copeptin using an automated immunofluorescence assay. In placebo-treated subjects, baseline copeptin predicted kidney growth and eGFR decline over 3 years. These associations were independent of sex, age, and baseline eGFR, but were no longer statistically significant after additional adjustment for baseline total kidney volume. In tolvaptan-treated subjects, copeptin increased from baseline to week 3 (6.3 pmol/L versus 21.9 pmol/L, respectively). In tolvaptan-treated subjects with higher baseline copeptin levels, a larger treatment effect was noted with respect to kidney growth rate and eGFR decline. Tolvaptan-treated subjects with a larger percentage increase in copeptin from baseline to week 3 had a better disease outcome, with less kidney growth and eGFR decline after three years. Copeptin holds promise as a biomarker to predict outcome and tolvaptan treatment efficacy in ADPKD.

AB - In the TEMPO 3:4 Trial, treatment with tolvaptan, a vasopressin V2 receptor antagonist, slowed the increase in total kidney volume and decline in estimated glomerular filtration rate (eGFR) in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether plasma copeptin levels, a marker of plasma vasopressin, are associated with disease progression, and whether pre-treatment copeptin and treatment-induced change in copeptin are associated with tolvaptan treatment efficacy. This post hoc analysis included 1,280 TEMPO 3:4 participants (aged 18-50 years, estimated creatinine clearance ≥60 ml/min and total kidney volume ≥750 mL) who had plasma samples available at baseline for measurement of copeptin using an automated immunofluorescence assay. In placebo-treated subjects, baseline copeptin predicted kidney growth and eGFR decline over 3 years. These associations were independent of sex, age, and baseline eGFR, but were no longer statistically significant after additional adjustment for baseline total kidney volume. In tolvaptan-treated subjects, copeptin increased from baseline to week 3 (6.3 pmol/L versus 21.9 pmol/L, respectively). In tolvaptan-treated subjects with higher baseline copeptin levels, a larger treatment effect was noted with respect to kidney growth rate and eGFR decline. Tolvaptan-treated subjects with a larger percentage increase in copeptin from baseline to week 3 had a better disease outcome, with less kidney growth and eGFR decline after three years. Copeptin holds promise as a biomarker to predict outcome and tolvaptan treatment efficacy in ADPKD.

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KW - tolvaptan

KW - vasopressin

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