Gabriella Aceto

von Willebrand factor and factor XIII in children with Henoch-Schonlein purpura.

Levels of von Willebrand factor antigen (vWf: Ag) and factor XIII activity (F XIII) were studied in relation to the severity of clinical symptoms (scored from 0 to 3) and to immunological parameters [IgA, C3, C4, and circulating immune complexes (CIC) in 16 children (7 males, 9 females, aged 3–11 years) with Henoch-Schonlein purpura (HSP) at presentation. vWf: Ag was increased in 7 patients, F XIII activity was decreased in 6. In all children we found high levels of IgA, while C3 and C4 levels were normal; CIC were elevated in 11. vWf: Ag correlated with clinical score and with IgA and CIC, probably as a result of immune-mediated endothelial cell damage. The haemostatic alterations observed in HSP are important for understanding the pathophysiology of the disease.

Urinary epidermal growth factor, monocyte chemotactic protein-1, and β2-microglobulin in children with ureteropelvic junction obstruction

BACKGROUND/PURPOSE We demonstrated down-regulation of epidermal growth factor (EGF) and up-regulation of monocyte chemotactic protein-1 (MCP-1) in the renal parenchyma in children who underwent pyeloplasty for ureteropelvic junction obstruction (UPJO). These findings were paralleled by urinary levels of EGF and MCP-1 before and after surgery. The aim of this study is to evaluate the urinary excretion of these cytokines and β2-microglobulin (β2M) in children with urine flow impairment at the ureteropelvic junction or who underwent pyeloplasty. METHODS Seventy-six patients with UPJO and 30 normal children (CTRL) were enrolled in the study. The UPJO patients were divided into obstructive (12), functional (36), and operated (28). Epidermal growth factor, MCP-1, and β2M urinary levels were measured by enzyme-linked immunosorbent assay and normalized to urine creatinine. RESULTS Urinary β2M and MCP-1 increased significantly in the UPJO groups compared with the CTRL and significantly improved in the operated group. The obstructive group displayed reduced EGF excretion compared with the CTRL group. The urinary (u)EGF/uMCP-1, and uEGF/uβ2M ratios significantly decreased in both untreated groups. In the operated group, these ratios improved significantly. CONCLUSIONS The present study substantiates the role of urinary EGF, MCP-1, and β2M as markers of tubulointerstitial damage in human obstructive nephropathy. Furthermore, it suggests that surgical intervention is effective in the management of children with UPJO.

High Sclerostin and Dickkopf-1 (DKK-1) serum levels in children and adolescents with type 1 diabetes mellitus

Context Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. Sclerostin and dickkopf-1 (DKK-1) are Wnt inhibitors that regulate bone formation. Objective To evaluate sclerostin and DKK-1 levels in T1DM children and to analyze the influence of glycemic control on bone health. Design and setting Cross-sectional study conducted at a clinical research center. Participants One hundred and six T1DM subjects (12.2 ± 4 years), 66 on multiple daily injections (MDIs) and 40 on continuous subcutaneous infusion of insulin (CSII), and 80 controls. Results The average bone transmission time (BTT) and amplitude-dependent speed of sound (AD-SoS) z scores were lower in patients with diabetes than in controls. Significantly increased DKK-1 (3593 ± 1172 vs 2652 ± 689 pg/mL; P < 0.006) and sclerostin (29.45 ± 12.32 vs 22.53 ± 8.29; P < 0.001) levels were found in patients with diabetes with respect to controls, particularly in patients on MDI compared with ones on CSII. Glycemic control was improved in CSII patients compared with MDI ones (P < 0.001) and was also associated with significantly higher BMI-SDS (P < 0.002) and BTT z scores (P < 0.02). With adjustment for age, multiple linear regression analysis of DKK-1 and sclerostin as dependent variables showed that levels of glycated hemoglobin, glucose, 25(OH) vitamin D, osteocalcin, and parathyroid hormone; years of diabetes; and BMI-SDS and AD-SoS z score were the most important predictors (P < 0.0001). Conclusions Our study highlighted (1) the high serum levels of DKK-1 and sclerostin in T1DM children and their relationship with altered glycemic control and (2) the effect of CSII on improvement of glycemic control and bone health in T1DM children.

End-stage renal disease secondary to IgA nephropathy in recessive dystrophic epidermolysis bullosa: a case report

Epidermolysis bullosa (EB) consists of a group of dominant or recessive autosomal diseases characterised by skin and mucosa fragility. The lesions leave erosions and scars that, in turn, can cause stenosis of tracheal, oesophageal, and genitourinary tract mucosae. The significantly increased survival of EB patients has determined the onset of complications never observed before, including genitourinary disorders such as hydroureteronephrosis, recurrent urinary tract infections, renal amyloidosis, IgA nephropathy and post-infectious glomerulonephritis. A 6-year-old boy diagnosed with recessive dystrophic EB Hallopeau–Siemens type (RDEB-HS) was referred to our clinic because of microhaematuria that evolved into intra-infectious macrohaematuria. Renal biopsy revealed an increase in both extracellular matrix and mesangial cells, with a focal segmental glomerulosclerosis with severe chronic tubulointerstitial damage. Immunofluorescence showed IgA mesangium deposits. Five years later, he was started on haemodialysis, because of worsening renal function. This is a rare case of a child with EB who was successfully treated with haemodialysis. The pertinent literature has been reviewed.

Laparascopic-assisted nephroureterectomy for shaped urolithiasis and xanthogranulomatous pyelonephritis: Case report and review of literature

We report a case of xanthogranulomatous pyelonephritis (XGP) complicated by shaped urolithiasis, severe hydroureteronephrosis and kidney exclusion treated by laparoscopic-assisted nephroureterectomy. A 9 year-old boy was referred to us for recurrent episodes of urinary tract infection, abdominal pain and severe hydronephrosis. Abdominal CT and a Tc-99m MAG3 scan showed a non-functioning obstructed kidney with shaped urolithiasis of the distal ureter. XGP was suspected, and nephroureterectomy was performed by laparoscopic distal ureterectomy and open extraperitoneal nephrectomy. This technique avoided the need for a more extended nephrectomy incision or even a second iliac incision. It also ensured complete excision of the distal ureter with minimal risk of developing the ureteral stump syndrome, which sometimes follows nephroureterectomy. We believe that laparoscopic-assisted nephroureterectomy may be a suitable technique in those cases of difficult nephrectomy where a ureteral stump syndrome is likely to develop.

Toll-free telephone medical information on nocturnal enuresis: the first Italian experience over a two-year period.

Purpose: The aim of the study is to promote, through this toll-free number (TFN) service, a health communication program providing information on nocturnal enuresis (NE) and related problems by a subspecialty-trained physician and to collect the callers’ characteristics too. All phone calls were scheduled to data collections. Methods: The telephone service operated as follows: the TFN was available from March 1 to May 31, 2000, and from April 1 to June 30, 2001. People called the free telephone line and received information needs. Results: A total of 12,806 calls were received by the help line during the two study periods (7,046 in 2000 and 5,760 in 2001). Of the calls, 61% came from subjects with NE without pharmacological or non-pharmacological treatment, 16% (2000) and 13% (2001) came from subjects >12 years old. Conclusions: A TFN for NE can be both accessible and effective in order to provide information on NE and related problems. Finally, such a service should be included in a national program to improve health and well-being.

Prospective Study on Several Urinary Biomarkers as Indicators of Renal Damage in Children with CAKUT

Purpose The aim of the study was to investigate urinary levels of monocyte chemotactic protein‐1 (MCP‐1), epidermal growth factor (EGF), &bgr;‐2‐microglobulin (&bgr;2M), and FAS‐ligand (FAS‐L) in children with congenital anomalies of kidney and urinary tract (CAKUT) disease at risk of developing glomerular hyperfiltration syndrome. For this reason, we selected patients with multicystic kidney, renal agenesia and renal hypodysplasia, or underwent single nephrectomy. Materials and Methods This prospective, multicentric study was conducted in collaboration between the Pediatric Surgery Unit in Foggia and the Pediatric Nephrology Unit in Bari, Italy. We enrolled 80 children with CAKUT (40 hypodysplasia, 22 agenetic; 10 multicystic; 8 nephrectomy) who underwent extensive urological and nephrological workup. Exclusion criteria were recent urinary tract infections or pyelonephritis, age > 14 years, presence of systemic disease, or hypertension. A single urine sample was collected in a noninvasive way and processed for measuring by enzyme‐linked immunosorbent assay urine levels of MCP‐1, EGF, &bgr;2M, and FAS‐L. As control, urine samples were taken from 30 healthy children. Furthermore, we evaluated the urinary ratios uEGF/uMCP‐1 (indicator of regenerative vs inflammatory response) and uEGF/u&bgr;2M (indicator of regenerative response vs. tubular damage). Results These results suggest that urinary levels of MCP‐1 are overexpressed in CAKUT patients. Furthermore, our findings clearly demonstrated that both uEGF/uMCP‐1 and uEGF/u&bgr;2M ratios were significantly downregulated in all patient groups when compared with the control group. Conclusion These findings further support that CAKUT patients may, eventually, experience progressive renal damage and poor regenerative response. The increased urinary levels of MCP‐1 in all groups of CAKUT patients suggested that the main factor responsible for the above effects is chronic renal inflammation mediated by local monocytes.

Clinical Characteristics and Management of Children with Ureteropelvic Junction Obstruction and Severe Vesicoureteral Reflux: Preliminary Results

ObjectiveThe aim of this study was to investigate the physiopathology of isolated or coexisting ureteropelvic junction obstruction (UPJ-O) and high-grade vesicoureteral reflux (VUR), including the clinical characteristics and management. Summary background dataThe association between UPJ-O and VUR was reported more frequently in boys with high-grade VUR; however, the physiopathology of concomitant UPJ-O and VUR is still unknown. Primary pyeloplasty, followed by ureteral reimplantation, if needed, has been widely accepted, although VUR should be treated first (most often by endoscopic treatment) in the presence of a functional obstruction. MethodsWe reviewed the charts of 78 children with isolated or coexisting high-grade VUR/UPJ-O. Among the children, 14 had isolated UPJ-O, 16 had high-grade VUR/UPJ-O, and 48 had high-grade VUR. Children with other urological or extrarenal conditions were excluded. ResultsPatients with isolated UPJ-O showed significantly different clinical characteristics compared with the other two groups of patients with high-grade VUR. Among the patients of group 2, 3/13 (23%) showed progression from functional to obstructive UPJ-O after endoscopic treatment. All of them underwent secondary pyeloplasty, which was complicated at follow-up by VUR recurrence needing further endoscopic injection. ConclusionWe suggest that UPJ-O in high-grade VUR patients is just a complication of severe VUR that produces structural changes in predisposed children. The treatment of children with associated high-grade VUR/UPJ-O may be complicated by the progression of urinary flow obstruction or VUR recurrence after pyeloplasty. Endoscopic treatment of high-grade VUR is associated with a high rate of VUR recurrence in children requiring subsequent pyeloplasty.

Unusual pediatric co-morbility: autoimmune thyroiditis and cortico-resistant nephrotic syndrome in a 6-month-old Italian patient

We report on a case of autoimmune thyroiditis in a 6-month-old patient with cortico-resistant nephrotic syndrome. Normal serum levels of thyroid hormons and thyroid-stimulating hormone were detected with high titers of circulant antithyroid antibodies and a dysomogeneous ultrasound appearance of the gland, typical of autoimmune thyroiditis. The research of maternal thyroid antibodies was negative. This is the first case of autoimmune thyroiditis found in such a young patient with pre-existing nephrotic syndrome ever described in literature. This association is random because nephrotic syndrome does not have an autoimmune pathogenesis and the genes involved in autoimmune thyroiditis are not related to those of nephrotic syndrome.

376 DETERMINATION OF von WILLEBRAND FACTOR AND FACTOR XIII IN CHILDREN WITH SCHONLEIN HENOCH SYNDROME

In 16 children (7 M and 9 F, aged between 4 and 11 years) with Schonlein Henoch Syndrome (SHS) at the onset, we have studied the levels of von Willebrand Factor Antigen (vWf:Ag) and Factor XIII activity (F XIII) in relation to the severity of clinical symptoms and the immunological parameters: IgA, C3, C4 and circulating immune complex (CIC). Arthral, abdominal and renal symptoms (except purpura) were scored from 0 to 3 and their mean values resulted respectively 1 ± 0,82; 1,13 ± 0,96; 1,38 ± 1,26 (total: 3,5 ± 1,59). The vWf:Ag resulted increased in 7 patients, the F XIII resulted decreased in 6. In all children we found high levels of IgA, while the C3 and C4 levels were normal. The CIC were elevated in 11. The total clinical score was positively correlated with vWf:Ag, IgA and CIC (p<0.05). The abdominal score was positively correlated with vWf:Ag (p<0.05); while the renal one with vWf:Ag (p<0.05) and CIC (p<0.001).Lastly vWf was correlated with IgA and CIC (p<0.05) and as in other systemic vasculites its level was increased in the acute phase of SHS probably in reference to immunomediated endothelial cell damage. In conclusion vWF levels are a good marker of SHS severity.