Formulation and Clinical Evaluation of Sodium Benzoate Oral Solution for the Treatment of Urea Cycle Disorders in Pediatric Patients.

BACKGROUND: Sodium benzoate, a common food preservative, is used in the treatment of patients with urea cycle disorders (UCDs) as it stimulates ammonia removal by a non-urea cycle-based pathway. Despite its use in the clinical routine, no commercially available oral formulations currently exist. Liquid formulation is normally well accepted in pediatric age and allows precise dosage according to the children's needs. AIMS: (1) To prepare an oral sodium benzoate solution in different tastes and determine its stability, palatability, and tolerability and (2) to describe the long-term follow-up of two pediatric patients with UCDs treated with our formulation. METHODS: We prepared five oral solutions of sodium benzoate (200 mg/ml) by adding different flavoring agents. We measured drug concentration in the samples by high-performance liquid chromatography (HPLC). We evaluated palatability and tolerability with adult volunteers. Long-term drug compliance and metabolic control were appraised in two pediatric patients. RESULTS: All the oral solutions remained stable at room temperature along the 96-day test period, and they were well tolerated. The mint-flavored solution resulted the most palatable and preferred by adult volunteers. We report good drug compliance and good metabolic outcomes for both pediatric patients during the entire follow-up. CONCLUSIONS: Our study highlighted the stability and tolerability of flavored sodium benzoate oral solutions. These solutions were well accepted during a long-term follow-up and guaranteed a good metabolic control. Since taste attributes are critical to ensure acceptable medication adherence in the pediatric age, flavored liquid formulations of sodium benzoate may be an efficient strategy to achieve therapeutic outcomes in UCD pediatric patients.

[Reflux nephropathy in absence of obvious vesicoureteral reflux]. / Nefropatia da reflusso in assenza di evidente reflusso vescicoureterale.

Although the majority of patients with vesicoureteric reflux presents DMSA scan alterations, parenchimal renal scars are found also in children without vesicoureteric reflux. Two clinical cases of reflux nephropathy without evidence of reflux are presented. Several explanations could be advocated to justify this picture, including haematogenous source of infection, inadequate timing and/or procedure of cystouretrography, intermittency of reflux, ascending bacteria, previous presence of reflux, and appearance of controlateral reflux during the natural history of a monolateral documented reflux. Tailored diagnostic and therapeutic strategy should discussed for each patient.

[Hematuria in pediatric clinical practice]. / L'ematuria in età pediatrica nella pratica clinica.

Haematuria, which was known at the time of Hippocrates, is defined as the presence of an anomalous number of red globules in the urine. It may present itself in a macroscopic or microscopic form. The latter is frequently found and is present in 1-2% of children. The pathogenesis of haematuria has been the object of recent acquisitions. The diagnosis is based in the first instance on the association of a positive urinary stick and confirmation of the presence of red globules in an assay of the sediment. The study of erythrocytic morphology is still the most useful test to identify the site of bleeding, even if more recently other markers, such as an excessive presence of acanthocytes or reduced mean corpuscle volume, together with the traditional study of cylindruria may represent elements to differentiate between glomerular and non-glomerular haematuria. Both family and personal medical history as well as objective examination play an important role in the definition of haematuria. Abdominal ultrasonography and biohumoral tests may, in association with the earlier data, allow a rapid and correct diagnosis of children with haematuria. A more detailed diagnosis using biopsy should be taken into consideration in selected cases, for example in familial forms that are not clearly defined and forms associated with altered renal function tests, as well as in persistent microhaematuria lasting for more than one year.

[Vesico-ureteral reflux in pediatrics]. / Il reflusso vescico-ureterale in pediatria.

Vesico-ureteral reflux (VUR) is the most frequent uropathy involving 1-2% of children. Genetics, familiarity, race gender and age intervene in the pathogenesis of VUR. In particular, neonatal VUR seems to represent a specific entity. Different factors determine a renal damage due to RVU: direct action of VUR (back pression), urinary tract infection (UTI), inflammatory mechanisms and renal dysplasia. Micturing cystourethrography and nuclear cystography are currently performed for the diagnosis of VUR, being ultrasound examination aspecific. Functional parameters are now investigated in association with new morphologic studies. The strict relationship of VUR and UTI is discussed. The treatment (medical, surgical) of VUR is not well established, although some guidelines can be suggested. Finally an adequate support must be given to the family for an optimal management.

[Renal calculosis in pediatrics]. / La calcolosi renale in pediatria.

Urinary stones (calculi) are not a rare problem in pediatrics, presenting a prevalence of 1 case/20,000 children/year. Both nephrocalcinosis (deposition of calculi within the renal parenchyma) and urolithiasis (stone formation in the calyces, renal pelvis and bladder) may occur. Etiology of urinary stones involves metabolic, infectious, anatomic and idiopathic causes. Diagnosis and treatment require knowledge of a wide range of diseases. After urinary stones have been suspected, biohumoral tests and ultrasound examination should be routinely performed.