Copeptin in Autosomal Dominant Polycystic Kidney Disease: Real-world Experiences from a Large Prospective Cohort Study

Overview

Journal Clin Kidney J

Publisher Oxford University Press

Specialty Nephrology

Date 2023 Nov 2

PMID 37915893

Authors

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 Muller

Affiliations

Soon will be listed here.

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. 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; < .0001) in all chronic kidney disease stages. Linear regression models ( = 133) show that copeptin is an independent predictor of eGFR slope. A clinical model (including eGFR, age, gender, copeptin) was nearly as good (R = 0.1196) as our optimal model (including height-adjusted total kidney volume, eGFR, copeptin, R = 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.

References

Chapman A, Devuyst O, Eckardt K, Gansevoort R, Harris T, Horie S . Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2015; 88(1):17-27. PMC: 4913350. DOI: 10.1038/ki.2015.59. View

Boertien W, Meijer E, Li J, Bost J, Struck J, Flessner M . Relationship of copeptin, a surrogate marker for arginine vasopressin, with change in total kidney volume and GFR decline in autosomal dominant polycystic kidney disease: results from the CRISP cohort. Am J Kidney Dis. 2012; 61(3):420-9. PMC: 3574620. DOI: 10.1053/j.ajkd.2012.08.038. View

Gansevoort R, van Gastel M, Chapman A, Blais J, Czerwiec F, Higashihara E . Plasma copeptin levels predict disease progression and tolvaptan efficacy in autosomal dominant polycystic kidney disease. Kidney Int. 2019; 96(1):159-169. PMC: 6640141. DOI: 10.1016/j.kint.2018.11.044. View

Devuyst O, Torres V . Osmoregulation, vasopressin, and cAMP signaling in autosomal dominant polycystic kidney disease. Curr Opin Nephrol Hypertens. 2013; 22(4):459-70. DOI: 10.1097/MNH.0b013e3283621510. View

Torres V . Salt, water, and vasopressin in polycystic kidney disease. Kidney Int. 2020; 98(4):831-834. DOI: 10.1016/j.kint.2020.06.001. View

Kramers B, Koorevaar I, Drenth J, De Fijter J, Neto A, Peters D . Salt, but not protein intake, is associated with accelerated disease progression in autosomal dominant polycystic kidney disease. Kidney Int. 2020; 98(4):989-998. DOI: 10.1016/j.kint.2020.04.053. View

Reif G, Yamaguchi T, Nivens E, Fujiki H, Pinto C, Wallace D . Tolvaptan inhibits ERK-dependent cell proliferation, Cl⁻ secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin. Am J Physiol Renal Physiol. 2011; 301(5):F1005-13. PMC: 3213906. DOI: 10.1152/ajprenal.00243.2011. View

Torres V, Abebe K, Schrier R, Perrone R, Chapman A, Yu A . Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney Int. 2016; 91(2):493-500. PMC: 5237414. DOI: 10.1016/j.kint.2016.10.018. View

Bankir L, Bichet D . What can copeptin tell us in patients with autosomal dominant polycystic disease?. Kidney Int. 2019; 96(1):19-22. DOI: 10.1016/j.kint.2019.02.037. View

10.

Corradi V, Martino F, Gastaldon F, Scalzotto E, Caprara C, Fortunato A . Copeptin levels and kidney function in ADPKD: case-control study. Clin Nephrol. 2016; 86(9):147-53. DOI: 10.5414/CN108894. View

11.

Zerbe R, Robertson G . Osmoregulation of thirst and vasopressin secretion in human subjects: effect of various solutes. Am J Physiol. 1983; 244(6):E607-14. DOI: 10.1152/ajpendo.1983.244.6.E607. View

12.

Morgenthaler N, Struck J, Alonso C, Bergmann A . Assay for the measurement of copeptin, a stable peptide derived from the precursor of vasopressin. Clin Chem. 2005; 52(1):112-9. DOI: 10.1373/clinchem.2005.060038. View

13.

Torres V, Chapman A, Devuyst O, Gansevoort R, Grantham J, Higashihara E . Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012; 367(25):2407-18. PMC: 3760207. DOI: 10.1056/NEJMoa1205511. View

14.

Torres V, Harris P, Pirson Y . Autosomal dominant polycystic kidney disease. Lancet. 2007; 369(9569):1287-1301. DOI: 10.1016/S0140-6736(07)60601-1. View

15.

Zittema D, van den Berg E, Meijer E, Boertien W, Muller Kobold A, Franssen C . Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients. Clin J Am Soc Nephrol. 2014; 9(9):1553-62. PMC: 4152815. DOI: 10.2215/CJN.08690813. View

16.

Raptis V, Loutradis C, Boutou A, Faitatzidou D, Sioulis A, Ferro C . Serum Copeptin, NLPR3, and suPAR Levels among Patients with Autosomal-Dominant Polycystic Kidney Disease with and without Impaired Renal Function. Cardiorenal Med. 2020; 10(6):440-451. DOI: 10.1159/000510834. View

17.

Torres V, Grantham J, Chapman A, Mrug M, Bae K, King Jr B . Potentially modifiable factors affecting the progression of autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol. 2010; 6(3):640-7. PMC: 3082424. DOI: 10.2215/CJN.03250410. View

18.

Gansevoort R, Arici M, Benzing T, Birn H, Capasso G, Covic A . Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol Dial Transplant. 2016; 31(3):337-48. PMC: 4762400. DOI: 10.1093/ndt/gfv456. View

19.

Ong A, Devuyst O, Knebelmann B, Walz G . Autosomal dominant polycystic kidney disease: the changing face of clinical management. Lancet. 2015; 385(9981):1993-2002. DOI: 10.1016/S0140-6736(15)60907-2. View

20.

Meijer E, Bakker S, Halbesma N, de Jong P, Struck J, Gansevoort R . Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort. Kidney Int. 2009; 77(1):29-36. DOI: 10.1038/ki.2009.397. View