Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children

Abstract

Context Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). Objective Characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA. Design and Setting Prospective observational multi-centre study. Patients and Intervention Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours. Main Outcome Measures Temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), associated between-subject variability [CV%]. Results Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95pmol/L (95%CI: 55-136) [CV%: 158%] to 9.7pmol/L (8.1-11.4) [31%] with a 50% recovery time (t1/2) of 7.1 (5.1-11.5) [114%] h. Serum osmolality decreased from 321mOsm/kg (315-327) [4%] to 294mOsm/kg (292-296) [1%] with t1/2 of 4.3 (3.0-5.6) [64%] h. Copeptin levels doubled with each osmolality increase by 15mOsm/kg (10-21) [59%], from 9.8pmol/L (7.3-12.3) [48%] at 280mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (P=0.0001), and less between mild versus moderate-severe DKA (P=0.044). Conclusions First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA.

Tubular injury in diabetic ketoacidosis: Results from the diabetic kidney alarm study

“…These differences were explained by the duration of diabetes and its known effects on osmoreceptor sensibility and on shifting the osmotic set point. 36,37 Our results confirm the findings of Burckhardt and colleagues, as children with newly diagnosed T1D in our study showed significantly higher copeptin concentration at 12-24 h than those with known T1D. Furthermore, metabolic acidosis interferes with vasopressin antidiuretic effects with a compensatory increase in vasopressin secretion by the neurohypophysis.…”

“…They also found that children with newly diagnosed T1D had higher concentrations of copeptin than those with known T1D after 12 h of DKA onset. These differences were explained by the duration of diabetes and its known effects on osmoreceptor sensibility and on shifting the osmotic set point 36,37 . Our results confirm the findings of Burckhardt and colleagues, as children with newly diagnosed T1D in our study showed significantly higher copeptin concentration at 12–24 h than those with known T1D.…”

“…found that copeptin concentrations are accentuated during DKA. 36 They also found that children with newly diagnosed T1D had higher concentrations of copeptin than those with known T1D after 12 h of DKA onset. These differences were explained by the duration of diabetes and its known effects on osmoreceptor sensibility and on shifting the osmotic set point.…”

“…Furthermore, elevated copeptin concentrations are associated with markers of tubular injury and with an increased risk of DKD 14,35 . Recently, Burckhardt et al found that copeptin concentrations are accentuated during DKA 36 . They also found that children with newly diagnosed T1D had higher concentrations of copeptin than those with known T1D after 12 h of DKA onset.…”

Acute Kidney Injury in Pediatric Diabetic Kidney Disease

“…Additionally, DKA has also been associated with early tubulopathy that may be caused by dysregulation of uric acid and vasopressin (58)(59)(60)(61)(62). Indeed, a recent study by Burckhardt et al found that copeptin, a surrogate marker for vasopressin, was elevated in children with DKA (63). Elevated copeptin concentrations have also been associated with markers of tubular injury and an increased risk for the development of DKD (62,64).…”