Rapid differential diagnosis of diabetes insipidus in a 7-month-old infant: The copeptin approach.

INTRODUCTION: Diabetes insipidus is characterized by hypoosmotic polyuria related to deficiency of arginine-vasopressin (AVP) secretion (central diabetes insipidus, CDI) or renal insensitivity to AVP (nephrogenic diabetes insipidus, NDI). The water deprivation test with assessment of AVP activity is currently the gold standard for differential diagnosis in patients presenting polyuria-polydipsia syndrome. Nevertheless, it can be dangerous without proper surveillance and its interpretation may be challenging. Other markers have been suggested. Direct quantification of circulating AVP is not sufficient for diagnosis: vasopressin is unstable, analysis is complex. AVP comes from prohormone preprovasopressin with concomitant release of copeptin (C-terminal moiety) in the equimolar ratio. Copeptin is stable in vitro, with easy and rapid measurement (<4h). Past studies have shown greater sensitivity and specificity of copeptin versus AVP to discriminate etiologies of polyuria in adults, but its value has not been demonstrated in infants yet. OBSERVATION: A 7-month-old infant presented polyuria-polydipsia syndrome with poor weight gain. Laboratory tests pointed out hypernatremia (170mmol/L) and blood hyperosmolarity (330mOsm/L) with inappropriate urinary hypoosmolarity (168mOsm/L). Plasmatic copeptin measurement was found at a very high level, 303pmol/L (1-14pmol/L). DdAVP administration did not improve the polyuria, confirming the final diagnosis of NDI. Hyperhydration with a hypoosmolar diet normalized the hydration status and circulating levels of copeptin within 1 week. CONCLUSION: Copeptin, a stable peptide reflecting AVP secretion, could be a safer and faster biomarker for etiological diagnosis of polyuria-polydipsia syndrome in children. Before regularization of hydration status, a single baseline measurement may be enough to discriminate NDI from other etiologies without the water deprivation test.

Adenosine plasma level correlates with homocysteine and uric acid concentrations in patients with coronary artery disease.

The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 µmol/L vs 0.53 ± 0.14 µmol/L; p < 0.01), HCys (15 ± 7.6 µmol/L vs 6.8 ± 3 µmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.

A2A adenosine receptor function in patients with vasovagal syncope.

AIMS: Adenosine is a possible mediator in vasovagal syncope (VVS) via the activation of its receptors. High expression of adenosine A2A receptors (A2AR) has been reported in VVS. The function of these over-expressed receptors in this population has never been evaluated. METHODS AND RESULTS: We used Adonis, a specific-made antibody with A2AR agonist properties, to evaluate binding parameters (i.e. dissociation constant KD) and cAMP production (i.e. EC50) by peripheral blood mononuclear cells of 16 VVS patients. Eight healthy volunteers served as controls. A2AR expression was higher in patients than controls; mean: 11.5 ± 1.2 vs. 7.7 ± 0.8 AU, P = 0.04. Also, KD values were higher in patients than controls: 2.1 ± 0.02 × 10(-7) vs. 5 ± 1 × 10(-8) M, P < 0.01 In controls, KD values were lower than EC50 (5 ± 1.7 × 10(-8) vs. 2.8 ± 0.4 10(-7) M, P < 0.01), but in patients, KD values did not differ from EC50: 2. ± 0.2 × 10(-7) vs. 2.5 ± 0.4 × 10(-7) M, P > 0.05. However, four patients had lower EC50 (3.5 ± 0.3 × 10(-8) M) than KD (2.9 ± 1.2 × 10(-7) M; KD/EC50 = 9.6), suggesting the presence of spare receptors. CONCLUSION: The function of A2AR of patients with VVS was preserved since their stimulation by Adonis led to cAMP production with an EC50 comparable with those in controls. However, their affinity was lower than those of controls. Our results suggest that A2AR are implicated in the physiopathology of VVS.