Long-term outcome after suicidal colchicine intoxication in a 14-year-old girl: case report and review of literature.

BACKGROUND: Colchicine is used as an anti-inflammatory drug in the treatment of gout, familial Mediterranean fever, and Behçet disease. However, because of its potent inhibition of mitosis, adverse effects and symptoms of intoxication are frequent. Clinical manifestations of colchicine intoxication include abdominal cramps, diarrhea, and multiorgan failure including cardiovascular collapse with fatal outcome. OBJECTIVE: We report here the case of a 14-year-old girl who ingested 12.5 mg (0.23 mg/kg body weight) colchicine in a suicide attempt. CASE REPORT: Major complaints of this fully conscious patient at the time of presentation ∼2 hours after ingestion of colchicine were nausea and impaired vision. Apart from a colchicine serum concentration of 16.2 ng/mL, no abnormalities were seen in the physical examination and blood tests. Gastrointestinal decontamination by activated charcoal, repeated administrations of sodium sulfate (Glauber salt) and substitution of volume and electrolytes led to complete recovery.

Lack of arginine vasopressin-induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus.

Water homeostasis in humans is regulated by vasopressin, which induces the translocation of homotetrameric aquaporin-2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells. For this process, phosphorylation of AQP2 at S256 by cAMP-dependent protein kinase A is thought to be essential. Mutations in the AQP2 gene cause recessive and dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin. Here, a family in which dominant NDI was caused by an exchange of arginine 254 by leucine in the intracellular C terminus of AQP2 (AQP2-R254L), which destroys the protein kinase A consensus site, was identified. Expressed in oocytes, AQP2-R254L appeared to be a functional water channel but was impaired in its transport to the cell surface to the same degree as AQP2-S256A, which mimics nonphosphorylated AQP2. In polarized renal cells, AQP2-R254L was retained intracellularly and was distributed similarly as AQP2-S256A or wild-type AQP2 in unstimulated cells. Upon co-expression in MDCK cells, AQP2-R254L interacted with and retained wild-type AQP2 in intracellular vesicles. Furthermore, AQP2-R254L had a low basal phosphorylation level, which was not increased with forskolin, and mimicking constitutive phosphorylation in AQP2-R254L with the S256D mutation shifted its expression to the basolateral and apical membrane. These data indicate that dominant NDI in this family is due to a R254L mutation, resulting in the loss of arginine vasopressin-mediated phosphorylation of AQP2 at S256, and illustrates the in vivo importance of phosphorylation of AQP2 at S256 for the first time.