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ROBO2 Gene Variants Are Associated with Familial Vesicoureteral Reflux

The SLIT2 receptor ROBO2 plays a key role in the formation of the ureteric bud, and its inactivation in mice leads to supernumerary ureteric bud development, lack of ureter remodeling, and improper insertion of the ureters into the bladder. Recently, two heterozygous ROBO2 missense mutations were identified in two families with primary vesicoureteral reflux occurring in combination with congenital anomalies of the kidney and urinary tract (VUR/CAKUT). This study investigated a possible causal role of ROBO2 gene variants in 95 unrelated patients with primary VUR (n = 78) or VUR/CAKUT. Eighty-two percent of all patients had a family history of genitourinary anomalies. Twenty-four ROBO2 gene variants were identified by direct sequencing of all 26 exons and the exon-intron boundaries. Of these, four led to amino acid substitutions: Gly328Ser, Asn515Ile, Asp766Gly, and Arg797Gln. When the families were examined, the missense variants co-segregated with VUR (three families) or VUR/CAKUT (one family). These variants were not found in 190 control subjects, and the affected amino acids have been conserved through evolution. In conclusion, a relatively high frequency of ROBO2 variants (5.1%) was found in familial cases; however, functional studies and validation in other cohorts are warranted.

Restoration of body composition in celiac children after one year of gluten-free diet.

Restoring protein, fat, and bone compartments in celiac children on a gluten-free diet (GFD) is not yet well understood. Hence, anthropometric, biochemical, and bone densitometric assessment was performed in 23 celiac children, 8 boys and 15 girls, aged 1 to 12 years (mean 4.7), at diagnosis and 1 year after GFD. At diagnosis the patients had height, arm muscle area, triceps skinfolds, subscapular skinfolds, fat area index, and bone mineral content significantly lower than in an age- and sex-matched control group. After 1 year on GFD, no significant difference was found between patients and controls in all the parameters studied except in height and arm muscle area, which, however, were very near to the normal expected. Serum hemoglobin, iron, and zinc values were below the normal range in more than one half of patients at diagnosis and within the normal range in almost all of them after 1 year of GFD. Serum hemoglobin, iron, zinc, triglycerides, proteins, albumin, and calcium values significantly rose during the year of GFD. A year of GFD in celiac children allows a virtually complete return in body mass composition.

Normal growth of nephrotic children during long-term alternate-day prednisone therapy

ABSTRACT. Statural growth has been evaluated in 20 prepubertal nephrotic children who received alternate‐day prednisone therapy for a year at least. Bone age was assessed in 16 of these children after 1‐4 years of therapy. During the follow‐up 12 children showed variations in height standard deviation score (SDs) below 0.5, 7 gained more than 0.5 SDs and 1 lost 0.5 SDs. Bone age fell within the normal range for chronological age in all the children studied. On the while alternate‐day prednisone therapy does not affect statural growth and bone maturation of children with lipoid nephrosis.

Recurrent Abdominal Pain in Childhood Urolithiasis

OBJECTIVE: Our goal was to establish the clinical presentation and features of pain attacks in children with recurrent abdominal pain (RAP) and urolithiasis. METHODS: We compared the rate of previous appendectomy among 100 consecutive patients with that of 270 control subjects. We also compared the frequency of pain attacks with that reported by children with functional or organic gastrointestinal RAP. RESULTS: Fifty-three patients had no history of dysuria or gross hematuria, and only 35 had hematuria at the first visit; 41 patients were evaluated for urolithiasis only because of a family history of kidney stones associated with RAP. Twenty-nine patients had been previously hospitalized for abdominal symptoms. Sixteen patients and 4 control subjects (1.5%) had undergone a previous appendectomy (P < .0001). Two to 28 months before the diagnosis of urolithiasis, 37 patients underwent abdominal ultrasonography, which did not show urinary stones. Sixty-nine percent of subjects younger than 8 years of age had central/diffuse abdominal pain. The mean frequency of pain attacks was 4 to 9 times lower than in patients with functional or organic gastrointestinal RAP. CONCLUSIONS: Because of the inconstant occurrence of dysuria and hematuria, the location of pain in areas other than the flank, and the lack of calculi shown on imaging studies performed after pain attacks, the urologic origin of pain may be overlooked and ineffective procedures performed. The possibility of urolithiasis should be considered in children with RAP who have a family history of urolithiasis and/or infrequent pain attacks, even when dysuria and hematuria are lacking, and in younger children even when pain is not lateral.

Statural growth of children with chronic renal failure on conservative treatment.

ABSTRACT. Statural growth was studied in 20 prepubertal children with chronic renal failure on conservative treatment followed‐up 1.1 to 8.9 years (average 3.9). Five children reached end‐stage renal failure during the follow‐up period and underwent dialysis or transplantation. Most patients grew at a normal rate. During the observation period only 1 out of 20 children lost more than 0.5 height standard deviation score whereas 9 gained 0.5 to 3.1. A growth velocity above the 97th percentile for at least 1 year was observed in 6 patients. A normal growth rate and even catch‐up growth is possible in children with chronic renal failure regardless of the degree of reduction of glomerular function.

Delayed Pubertal Growth Spurt and Normal Adult Height Attainment in Boys Receiving Long-term Alternate-day Prednisone Therapy

Statural growth to age ≥20 years was studied in 10 boys with glomerulonephritis who received alternate-day prednisone (mean 1.2 mg/kg) for at least 2 consecutive years during pubertal age. Peak growth velocity was delayed after age 15 years in six patients and it was less than 7 cm/year in five. However, after age 16, growth velocity was significantly (p 0.02) higher than expected and allowed patients to ultimately reach their genetic height potential.

Hepatitis B Surface Antigenaemia and Glomerulopathies in Children

ABSTRACT. Serum HBsAg positivity prevalence was studied on 98 children affected by various nephropathies or obstructive uropathies and on a control group of 71 children, consecutively admitted into the same clinical ward, suffering from other than hepatic or renal diseases. No significant difference was found between the group of children with non‐glomeruiar nephropathies or obstructive uropathies and the control group. The prevalence of HBsAg positivity was significantly higher in male children with membranous glomerulopathy and in those with lipoid nephrosis than in the control group. All HBsAg positive children with glomerulopathies were chronic carriers of the hepatitis B virus. However, though left undemonstrated, there still lies a probable pathogenetic relationship between the hepatitis B virus infection and membranous glomerulopathy. The authors hypothesize that an impaired immune response in male children with lipoid nephrosis may account for both the hepatitis B virus infection and the development of the glomerular disease.

Outcomes of a Cohort of Prenatally Diagnosed and Early Enrolled Patients with Congenital Solitary Functioning Kidney

Purpose: We evaluated the clinical course of patients prenatally diagnosed and enrolled early with congenital solitary functioning kidney, and identified the risk factors for renal injury. Materials and Methods: We retrospectively evaluated 322 patients with congenital solitary functioning kidney according to the inclusion criteria of 1) prenatal diagnosis of solitary kidney; 2) first evaluation at 1 to 3 months of life with confirmation of congenital solitary functioning kidney, and evaluation of possible associated congenital anomalies of the kidney and urinary tract by abdominal ultrasound, renal scintigraphy and cystography; and 3) absence of any condition potentially affecting renal function in the neonatal period as well as absence of renal injury at enrollment (1 to 3 months of life) confirmed by a normal estimated glomerular filtration rate, lack of proteinuria and hypertension. Followup of 306 patients was evaluated. Results: Median followup was 7.2 years (range 1 to 23) and 1 or more signs of renal injury were found in 12 of 306 patients (3.9%). Considering the entire population the cumulative proportion of patients free from renal injury at 17 years old was 93.7%, vs 81.3% and 95.9% for subjects with and those without congenital anomalies of the kidney and urinary tract of congenital solitary functioning kidney (p <0.001), respectively. Of congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney resulted in significant risk factors for renal injury (HR 8.75, 95% CI 2.77–27.65). Conclusions: In an evaluation of a large cohort of patients enrolled early with congenital solitary functioning kidney with a prenatal diagnosis, excluding those with neonatal onset of renal damage, the prevalence of renal damage was 3.9%. Among congenital anomalies of the kidney and urinary tract, congenital solitary functioning kidney represented the major risk factor.

Weight overgrowth of coeliac children on gluten-free diet

Abstract Linear and weight growth were assessed in 17 coeliac children on gluten-free diet and followed up for 2 to 7 years (mean 3.8). Mean height was −0.85 height standard deviation scores at first visit, −0.19 after one year and 0.03 at last visit. Weight for Height Index (WHI) was 88.8% at first visit, 111.9 after one year and 111.6 at last visit. WHI values of patients at one year and at last visit were significantly higher than the 100% expected, even after excluding the subjects having at least one parent with body mass index >30 and/or at least one sibling with WHI >120%. A dietary recall at the end of the follow-up revealed an excess in caloric, animal protein and lipid intake and an absolute or relative deficit in complex sugars and vegetal proteins. The exclusion of gluten containing foods from the diet of coeliac children carries the risk of intake of hypercaloric foods, which may lead to some degree of obesity.

Effect of gluten-free diet on bone mineral metabolism of celiac children

Abstract Studies on the effects of gluten-free diet (GFD) on bone mineral metabolism have given no univocal results in children and adults with celiac disease. Bone mineral metabolism was assessed in 23 celiac children, aged 1 to 12 years (mean 4.6) at moment of diagnosis (T 0 ) and after 12 months of GFD (T 12 ) without any vitamin D supplementation. At T 0 , calcium, phosphates and alkaline phosphatase values were within the normal range in all but few subjects, but their respective average values significantly rose at T 12 . The percentages of low values of bone mineral density and of osteocalcin at T 0 were significantly higher than those at T 12 and their respective average values significantly increased between T 0 and T 12 . Circulating parathyroid hormone values were within the normal range in all patients at T 0 and T 12 , with no significant difference in average values between T 0 and T 12 . One year of GFD is sufficient to obtain a complete restoration of bone mineral density even without vitamin D supplementation. The normal levels of parathyroid hormone and the reduced osteocalcin at diagnosis suggest that in young celiac children there is no important rise in bone remodeling.