SUMMARYThe syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients' SIADH-like clinical picture, which we have termed "nephrogenic syndrome of inappropriate antidiuresis."Fluid homeostasis depends on proper water intake, governed by an intact thirst mechanism, and on urinary excretion of free water, mediated by appropriate secretion of arginine vasopressin (AVP) (also known as antidiuretic hormone). 1 AVP exerts its antidiuretic action by binding to the V2 vasopressin receptor (V2R), a G protein-coupled receptor, on the basolateral membrane of epithelial cells in the collecting duct of the kidney. Ligand binding activates the V2R, stimulating adenylate cyclase by means of G s proteins. The resulting increase in intracellular cyclic AMP (cAMP) promotes shuttling of intracellular vesicles containing the water channel aquaporin-2 to the apical membrane of the collecting-duct cells, thereby increasing water permeability and inducing antidiuresis.Clinical disorders of water balance are common, and alterations in many steps of this pathway have been described. 1 Urinary concentrating defects associated with diabetes insipidus may result from a deficiency of AVP or from nephrogenic causes, such as Xlinked, inactivating mutations in the V2R or autosomal recessive or autosomal dominant lesions in aquaporin-2. 2 Conversely, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) manifests as an inability to excrete a free water load, with inappropriately concentrated urine and resultant hyponatremia, hypo-osmolality, and We describe two unrelated male infants whose clinical presentation was consistent with the presence of chronic SIADH but who had undetectable AVP levels. We postulated that novel activating mutations of the V2R might account for their unique presentation. Evaluation revealed novel activating mutations of the V2R leading to what we term "nephrogenic syndrome of inappropriate antidiuresis" (NSIAD). HHS Public Access CASE REPORTSPatient 1 presented at 3 months of age with irritability, and Patient 2 presented at 2.5 months of age with two generalized seizures. Both children had had unremarkable early neonatal courses. Both were exclusively bottle-fed formula (7 mmol of sodium per liter). Both infants had mild systolic hypertension with otherwise normal physical examinations. Initial laboratory evaluations demonstrated hyponatremia with normal serum levels of potassium and bicarbonate (Table 1). Both children had serum hypo-o...

MAS presents with significant involvement of visceral arteries with over two thirds of cases having renal artery stenosis, and one third with superior mesenteric artery stenosis. The extent of disease is worse among those with genetic and inflammatory conditions. Further studies are needed to better understand etiology, long-term effectiveness of treatment, and to determine the optimal management of this potentially devastating condition.

Successful transition from paediatric-centred to adult-oriented healthcare positively influences health outcomes for youth with chronic illness. The primary objective is to evaluate outcomes pre- and post provision of multidisciplinary transition clinic (TC) care to renal transplant recipients. We compared patient and allograft survival in renal transplant recipients at British Columbia Children's Hospital who received care within a transition clinic (TC) to a cohort of patients transferred prior to establishment of the TC, pre-TC (PTC) in 2007. Baseline characteristics, allograft function, and survival data were collected prospectively via a validated provincial database for 2 years posttransfer. We also estimated and compared the average yearly per-patient cost during the 2-year follow-up period. Thirty-three patients were transferred (PTC) and 12 transitioned (TC). In the PTC cohort, there was a combined poor outcome (death or allograft loss) incidence of 24% within 2 years posttransfer compared with no death or allograft loss in the TC cohort. Cost estimates indicate the average yearly per-patient cost was Canadian dollars (CAD) $17,127-$38,909 for the PTC and CAD $11,380-$34,312 for the TC cohort. For PTC patients who lost their allograft and returned to dialysis, the per-patient cost was CAD $40,956-$61,470. Our results indicate improved allograft and patient survival posttransfer of care in renal transplant recipients who attended TCs, and we found that providing TCs is economically feasible.

Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology-Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.