Copeptin in autosomal dominant polycystic kidney disease: real-world experiences from a large prospective cohort study

Sita Arjune; Simon Oehm; Polina Todorova; Ron T Gansevoort; Stephan J L Bakker; Florian Erger; Thomas Benzing; Volker Burst; Franziska Grundmann; Philipp Antczak; Roman-Ulrich Müller

doi:10.1093/ckj/sfad118

Copeptin in autosomal dominant polycystic kidney disease: real-world experiences from a large prospective cohort study

Clin Kidney J. 2023 May 25;16(11):2194-2204. doi: 10.1093/ckj/sfad118. eCollection 2023 Nov.

Authors

Sita Arjune^{1

2

3

4}, Simon Oehm¹, Polina Todorova¹, Ron T Gansevoort⁵, Stephan J L Bakker⁵, Florian Erger^{3

6}, Thomas Benzing^{1

2

3

4}, Volker Burst^{1

7}, Franziska Grundmann¹, Philipp Antczak^{1

4}, Roman-Ulrich Müller^{1

2

3

4}

Affiliations

¹ Department II of Internal Medicine, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
² Center for Molecular Medicine Cologne, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
³ Center for Rare Diseases Cologne, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁴ Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
⁵ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Institute of Human Genetics, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
⁷ Emergency Department, University of Cologne, Faculty of Medicine and University Hospital of Cologne , Cologne, Germany.

Abstract

Background: The identification of new biomarkers in autosomal-dominant polycystic kidney disease (ADPKD) is crucial to improve and simplify prognostic assessment as a basis for patient selection for targeted therapies. Post hoc analyses of the TEMPO 3:4 study indicated that copeptin could be one of those biomarkers.

Methods: Copeptin was tested in serum samples from patients of the AD(H)PKD study. Serum copeptin levels were measured using a time-resolved amplified cryptate emission (TRACE)-based assay. In total, we collected 711 values from 389 patients without tolvaptan treatment and a total of 243 values (of which 64 were pre-tolvaptan) from 94 patients on tolvaptan. These were associated with rapid progression and disease-causing gene variants and their predictive capacity tested and compared with the Mayo Classification.

Results: As expected, copeptin levels showed a significant negative correlation with estimated glomerular filtration rate (eGFR). Measurements on tolvaptan showed significantly higher copeptin levels (9.871 pmol/L vs 23.90 pmol/L at 90/30 mg; P < .0001) in all chronic kidney disease stages. Linear regression models (n = 133) show that copeptin is an independent predictor of eGFR slope. A clinical model (including eGFR, age, gender, copeptin) was nearly as good (R² = 0.1196) as our optimal model (including height-adjusted total kidney volume, eGFR, copeptin, R² = 0.1256). Adding copeptin to the Mayo model improved future eGFR estimation.

Conclusion: Copeptin levels are associated with kidney function and independently explained future eGFR slopes. As expected, treatment with tolvaptan strongly increases copeptin levels.

Keywords: ADPKD; biomarker; copeptin; tolvaptan; vasopressin.