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

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 (R(2) = 0.1196) as our optimal model (including height-adjusted total kidney volume, eGFR, copeptin, R(2) = 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.