The Effect of Renal Function and Hemodialysis Treatment on Plasma Vasopressin and Copeptin Levels

Abstract

IntroductionCopeptin is increasingly used in epidemiological studies as a substitute for vasopressin. The effect of renal function per se on copeptin and vasopressin concentrations as well as their ratio have, however, not been well described.MethodsCopeptin and vasopressin levels were measured in 127 patients with various stages of chronic kidney disease, including 42 hemodialysis patients and 16 healthy participants in this observational study. Linear (segmental) regression analyses were performed to assess the association between renal function and copeptin, vasopressin and the C/V ratio. In addition, clearance of copeptin and vasopressin by hemodialysis was calculated.ResultsBoth copeptin and vasopressin levels were higher when renal function was lower, and both showed associations with plasma osmolality. The C/V ratio was stable across renal function in subjects with an eGFR >28 ml/min per 1.73 m2. In contrast, the C/V ratio increased with worsening renal function in patients with eGFR ≤28 ml/min per 1.73 m2. During hemodialysis, the initial decrease in vasopressin levels was greater compared with copeptin and, consequently, the C/V ratio increased. This was, at least in part, explained by a greater dialytic clearance of vasopressin compared with copeptin.DiscussionOur data indicate that copeptin is a reliable substitute for vasopressin in subjects with an eGFR >28 ml/min per 1.73 m2, whereas at an eGFR ≤28 ml/min per 1.73 m2, that is, CKD stages 4 and 5, a correction for renal function is required in epidemiological studies that use copeptin as a marker for vasopressin. Intradialytic copeptin levels do not adequately reflect vasopressin levels because vasopressin clearance by hemodialysis is higher than that of copeptin.

Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5

“…Our study showed positive correlation between plasma osmolality and copeptin in the group of nondialyzed CKD5 patients, whereas such relationship was not observed in PD and HD groups, and nondialyzed patients had also lower plasma copeptin levels than the other two groups. This accords with Ettema et al [32] who examined copeptin levels in patients with different stages of CKD, including CKD5. They observed positive correlation between plasma osmolality and copeptin in patients with CKD and higher residual renal function (RRF) associated with lower plasma copeptin levels in HD patients which underscore the importance of RRF in the clearance of copeptin.…”

“…Finally, although the circulating concentration of copeptin directly reflects that of AVP and copeptin shows the same response to osmotic changes as AVP in CKD, copeptin is reported to increase more than vasopressin suggesting that the clearance rate of copeptin is more markedly reduced than for vasopressin when GFR decreases. Thus, while copeptin reflects vasopressin levels, in CKD stages 4 and 5, a correction for renal function might be required [14,32].…”

Plasma copeptin and chronic kidney disease risk in 3 European cohorts from the general population

“…Although their plasma concentrations correlate over a wide range of plasma and/or urine osmolalities, the strength of the correlation might vary with the GFR (14). However, the correlation seems relatively stable for eGFR > 30 ml/min/1.73 m 2 (43), which corresponds to all but 8 of the participants in…”

“…Both vasopressin and copeptin are small-sized molecules and thus could be subjected to renal clearance. However, results from a recent investigation suggest that renal clearance is not the predominant factor in the degradation of circulating copeptin (43). Moreover, strong experimental data have been accumulated in the last decades supporting a direct causal role for vasopressin in the pathogenesis of CKD (15).…”

The Vasopressin System in the Risk of Diabetes and Cardiorenal Disease, and Hydration as a Potential Lifestyle Intervention

“…Copeptin correlates well with vasopressin levels and can be measured reliably in plasma over a wide range of physiological changes in plasma osmolality [25][26][27] viduals with estimated glomerular filtration rate (eGFR) >28 mL/min/1.73 m 2 . A correction for renal function may be required below this level of eGFR [28].…”