Fluid management in children with volume depletion.

Volume depletion is a common condition and a frequent cause of hospitalization in children. Proper assessment of the patient includes a detailed history and a thorough physical examination. Biochemical tests may be useful in selected cases. Understanding the pathophysiology of fluid balance is necessary for appropriate management. A clinical dehydration scale assessing more physical findings may help to determine dehydration severity. Most dehydrated children can be treated orally; however, intravenous therapy may be indicated in patients with severe volume depletion, in those who have failed oral therapy, or in children with altered consciousness or significant metabolic abnormalities. Proper management consists of restoring circulatory volume and electrolyte balance. In this paper, we review clinical aspects, diagnosis, and management of children with volume depletion.

Therapeutic Response to Corticosteroids Remains a Valid Approach to Initial Management of Children With Idiopathic Nephrotic Syndrome.

Complete remission of idiopathic nephrotic syndrome (INS) in response to corticosteroids has been widely adopted as an indicator of satisfactory long-term outcomes in pediatric patients. The approach was based on the results of studies conducted in the 1960s and 1970s. The studies found that corticosteroid-responsive minimal change disease (MCD) was the most frequent diagnosis in INS patients. In more recent years, studies have reported increased frequency of focal segmental glomerulosclerosis (FSGS) and primary corticosteroid resistance without a corresponding increase of FSGS. It became unclear whether withholding kidney biopsy before treatment with corticosteroids is still the best management practice. We performed a retrospective chart review at the UPMC Children's Hospital of Pittsburgh and identified patients who were referred for evaluation of edema or proteinuria between 2002 and 2014. We identified 114 pediatric patients with INS who were treated initially with a corticosteroid (prednisone or prednisolone) 2 mg/kg (max 60 mg)/day for 4-6 weeks followed by 2 mg/kg (max 60 mg) every other day for 4-6 weeks and had not received a corticosteroid-sparing agent before completing at least 8 weeks of the initial therapy. Corticosteroid resistance in pediatric INS patients was independently associated with the black race, older age at presentation (>8 years), and female sex. The majority of blacks who were resistant to corticosteroids had a tissue diagnosis of MCD. Among the whites who were steroid-resistant, MCD and FSGS were diagnosed in similar proportions of cases. Thus, the tissue diagnosis in could not predict the response to corticosteroids. Nineteen percent of whites with FSGS were steroid-sensitive and none of the blacks with FSGS responded to corticosteroids. These data suggest that the histologic diagnosis of FSGS could not rule out response to corticosteroids, at least, in the white patient population. In summary, our data demonstrate that at this time, the therapeutic response to corticosteroids continues to be a valid approach for the initial evaluation and therapy of children diagnosed with INS at our center. Future studies should evaluate the mechanisms of changing characteristics of pediatric INS. The specific role of patient demographics, ethnicity, as well as genetic and environmental factors could be evaluated by a prospective, multicenter study.

Loss of peri-Wolffian duct stromal Frs2α expression in mice leads to abnormal ureteric bud induction and vesicoureteral reflux.

BackgroundFibroblast growth factor receptor 2 (Fgfr2) deletion from murine peri-Wolffian duct stroma (ST) results in aberrant ureteric bud induction, abnormal ureteral insertion into the bladder, and high rates of vesicoureteral reflux (VUR). It is unclear which receptor docking protein(s) is/are responsible for Fgfr2 actions in these tissues. We investigated whether the docking protein, fibroblast receptor substrate 2α (Frs2α), had a role in peri-Wolffian duct ST similar to Fgfr2.MethodsWe conditionally deleted Frs2α in peri-Wolffian duct ST with a Tbx18cre mouse line (Frs2αST-/-). We assessed for ureteric induction defects and alterations in downstream targets mediating defects. We performed euthanized cystograms and assessed ureter-bladder junctions by three-dimensional (3D) reconstructions.ResultsEmbryonic day (E) 11.5 Frs2αST-/- embryos had many displaced ureteric bud induction sites when compared with controls. E11.0 Frs2αST-/- embryos had decreased Bmp4 expression and signaling, which can cause abnormal ureteric bud induction. Postnatal day 1 (P1) and P30 Frs2αST-/- mice had higher VUR rates and grades vs. CONTROLS: Mutant refluxing ureters that inserted improperly into the bladder had shortened intravesicular tunnels (IVTs) when compared with controlsConclusionFrs2αST-/- embryos have aberrant ureteric induction sites, improper ureteral insertion, shortened intravesicular lengths, and VUR. Induction site defects appear secondary to reduced Bmp4 expression, similar to Fgfr2 mutants.