Abstract
BACKGROUND: Plasma copeptin, a marker of vasopressin, is associated with renal function decline in the general population. Our aim was to study the links between elevated copeptin and future risk of kidney disease. METHODS: Copeptin was measured in a sample of the Malmö Preventive Project (MPP) Reinvestigation (n = 5158) and in the Malmö Diet and Cancer Cardiovascular Cohort (MDC-CC) (n = 5162). According to national registers, 89 subjects in MPP and 180 in MDC-CC developed chronic kidney disease (CKD) during follow-up (8.7 and 19.6 years, respectively). RESULTS: After multivariate adjustment (gender, age, body mass index, smoking status, estimated glomerular filtration rate, prevalent diabetes, systolic blood pressure and prevalent antihypertensive treatment), copeptin (beta-coefficient per 1 standard deviation increment of ln copeptin) was independently associated with increased risk of CKD during follow-up in both cohorts (MPP: (HR) 1.46, 95% confidence interval (CI) 1.18-1.80, P < 0.001; MDC-CC: HR 1.25, 95% CI 1.02-1.54, P = 0.03) among subjects free from prevalent kidney disease at baseline. Furthermore, in MPP, elevated copeptin predicted a specified diagnosis of kidney disease other than CKD (HR 1.31, 95% CI 1.08-1.59, P = 0.006) after multivariate adjustment. In a corresponding analysis in MDC-CC, copeptin was associated with a 10% increased risk, which, however, was non-significant (P = 0.25). A meta-analysis of the MPP and MDC-CC data showed significant association between elevated copeptin and a specified diagnosis of kidney disease other than CKD (HR 1.18, 95% CI 1.05-1.34, P = 0.008). CONCLUSION: An increased level of copeptin independently predicts development of both CKD and other specified kidney diseases, suggesting that copeptin can be used to identify individuals at risk for kidney disease development.