Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Abstract

Background: Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). Methods: We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) <60 (CKD_60_MDRD), <45 (CKD_45_MDRD) and <30 (CKD_30_MDRD) ml/min/1.73 m². Results: After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m²) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p < 0.001). Each SD increment of copeptin independently predicted incident CKD_60_MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45_MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30_MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. Conclusion: Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.

Shifting Focus: From Hydration for Performance to Hydration for Health

“…Over the past several years, plasma copeptin has also been measured in some cohort studies, allowing for associations to be made with health outcomes. Copeptin has been independently associated with diabetes, metabolic syndrome, abdominal obesity, metabolic heart disease, and death [34][35][36][37] , as well as with GFR decline and progression toward CKD [47,48] . One limitation is that widespread copeptin measurement is relatively new, and thus the number of large cohorts is limited.…”

“…A majority of the available results were obtained from analyses performed on the Malmö Diet and Cancer Study (Sweden) and D.E.S.I.R. (France) cohorts [47,48] . One major strong point of the analyses, however, is that copeptin remained an independent risk factor after controlling for covariates most often associated with kidney and metabolic disease.…”

Two Liters a Day Keep the Doctor Away? Considerations on the Pathophysiology of Suboptimal Fluid Intake in the Common Population

“…Increased plasma vasopressin levels are reflected by a similar increase of the surrogate marker copeptin, a protein released in parallel to vasopressin but more stable than vasopressin and thus reflecting the integrated hydration status more reliably [17]. Individuals with copeptin levels in the top 25% of the general population were shown to have markedly increased risk of developing type 2 diabetes independently of known diabetes risk factors [18], a finding subsequently replicated in different populations [19, 20].…”

“…Individuals with copeptin levels in the top 25% of the general population were shown to have markedly increased risk of developing type 2 diabetes independently of known diabetes risk factors [18], a finding subsequently replicated in different populations [19, 20]. Along those lines, genetic variance of the vasopressin receptor AVPR1B is associated with overweight and diabetes [17, 21]. Rats with high vasopressin levels had higher fasting glucose levels than rats with low vasopressin levels [22].…”

“…Interestingly, high copeptin is also associated with a broad range of other diseases such as heart failure [28], vascular dementia [27], cognitive impairment [29], microalbuminuria [25], chronic kidney disease [17, 30], inflammatory bowel disease [31], cancer [32], and premature mortality [24]. …”