Renal Function

At normal concentrations, the role of AVP is to regulate the plasma osmolality by eliminating free water in the kidney. Like mature AVP, copeptin is regulated within a certain normal range, but may fluctuate according to individual physiologic conditions. Copeptin increases to upper normal values during fasting and shows a rapid decline in vivo to low normal values after oral water load.Ref-4 In a study of 24 healthy volunteers, copeptin showed identical changes during disordered water states or osmolality to those previously shown for AVP: water deprivation, which resulted in weight loss and an increase in plasma osmolality, increased serum copeptin. Additional infusion of hypertonic saline increased copeptin even further to plasma values not usually seen in healthy individuals. Conversely, during hypotonic saline infusion, plasma osmolality decreased and copeptin decreased to values in the very low normal range.Ref-21

Electroloyte disturbances are common in cardiovascular and renal diseases, including the most commonly seen hyponatremia, and the pathophysiology is complex and the diagnostic approach is challenging.Ref-60 Copeptin plasma concentrations might be valuable in the diagnostic work-up of hyponatremic conditions, which have been reported in up to 15% of hospitalized patients,Ref-61 sometimes with a poor prognosis. In patients with SIADH, determination of copeptin together with urine sodium helped in the differential diagnosis.Ref-23

Furthermore, in many hospital situations, such as after surgery, the release of AVP is nonosmotic, due to pain, anxiety, nausea, or the use of pharmacologic agents. Often hypotonic fluids are given without prior assessment of AVP levels, potentially resulting in hyponatremia, a scenario quite common in pediatric medicine.Ref-62 Here, copeptin measurements may offer additional information for the fluid therapy of the postsurgical patient.

In renal disease, albuminuria is a powerful predictor of progressive cardiovascular and renal failure. Administration of an AVP agonist to rats and humans induced albuminuria,Ref-63, 64 and lowering AVP by drinking or a V2-receptor antagonist reduced proteinuria in rats with renal failure.Ref-65-67 It is still unclear, if this is due to a direct effect of AVP on albumin excretion, or secondary to the AVP effect on circulating blood volume and blood pressure. In a recent population study (PREVEND, Prevention of Renal and Vascular End Stage Disease), which included adults with and without kidney dysfunction, Meijer and Gansevoort report on an association between copeptin and microalbuminuria that suggests a direct effect of AVP on urinary albumin excretion.Ref-68 Microalbuminuria (urinary albumin excretion of at least 30 mg/24 hours) was about two times more prevalent in individuals with copeptin plasma levels in the highest quintile (> 10.5 pmol/L) compared with individuals with copeptin levels in the lowest two quintiles (< 5.3 pmol/L). This association was independent of age and other potential confounders. If this hypothesis is confirmed in other studies, it may have direct implications on the prevention and control of renal disease.Ref-69

The same group also examined the role of copeptin baseline values and the change in renal function during follow-up in a cohort of 548 renal transplant recipients.Ref-70 Whilst the relationship at baseline between copeptin values, plasma osmolality, and urinary sodium concentration was consistent with normal physiology, elevated copeptin concentration was associated with an accelerated renal function decline in patients with renal transplants, as seen by a decrease in glomerular filtration rate over a median follow-up period of 3.6 years. Again, this association seemed to be independent of other risk factors for renal function decline in renal transplant recipients, and the association was similar in magnitude to other well-known factors of renal function decline, such as baseline mean arterial pressure or glucose. Intervention studies using V2-receptor antagonists seem to be justified, and copeptin may serve as a biomarker to identify patients with renal transplants who may benefit from treatment with those drugs.Ref-71


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