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

Tempo 3 4 Investigators, Jul-2019, In : Kidney International. 96, 1, p. 159-169 11 p.

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  • Plasma copeptin levels predict disease progressionand tolvaptan efficacy in autosomaldominant polycystic kidney disease

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  • Tempo 3 4 Investigators

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 pretreatment 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
Pages (from-to)159-169
Number of pages11
JournalKidney International
Volume96
Issue number1
Early online date9-Mar-2019
Publication statusPublished - Jul-2019

    Keywords

  • ADPKD, AVP, copeptin, polycystic kidney disease, tolvaptan, vasopressin, RENAL CONCENTRATING CAPACITY, SURROGATE MARKER, FUNCTION DECLINE, CYST GROWTH, VASOPRESSIN, URINE, MODEL, POPULATION, OSMOLALITY, DISORDERS

ID: 78802168