Value of imaging studies after a first febrile urinary tract infection in young children: data from Italian renal infection study 1.

OBJECTIVE: We examined the diagnostic accuracy of routine imaging studies (ultrasonography and micturating cystography) for predicting long-term parenchymal renal damage after a first febrile urinary tract infection. METHODS: This study addressed the secondary objective of a prospective trial evaluating different antibiotic regimens for the treatment of acute pyelonephritis. Data for 300 children < or =2 years of age, with normal prenatal ultrasound results, who completed the diagnostic follow-up evaluation (ultrasonography and technetium-99m-dimercaptosuccinic acid scanning within 10 days, cystography within 2 months, and repeat technetium-99m-dimercaptosuccinic acid scanning at 12 months to detect scarring) were analyzed. Outcome measures were sensitivity, specificity, and negative and positive predictive values for ultrasonography and cystography in predicting parenchymal renal damage on the 12-month technetium-99m-dimercaptosuccinic acid scans. RESULTS: The kidneys and urinary tracts were mostly normal. The acute technetium-99m-dimercaptosuccinic acid scans showed pyelonephritis in 54% of cases. Renal scarring developed in 15% of cases. The ultrasonographic and cystographic findings were poor predictors of long-term damage, showing minor sonographic abnormalities for 12 and reflux for 23 of the 45 children who subsequently developed scarring. CONCLUSIONS: The benefit of performing ultrasonography and scintigraphy in the acute phase or cystourethrography is minimal. Our findings support (1) technetium-99m-dimercaptosuccinic acid scintigraphy 6 months after infection to detect scarring that may be related to long-term hypertension, proteinuria, and renal function impairment (although the degree of scarring was generally minor and did not impair renal function) and (2) continued surveillance to identify recurrent urinary tract infections that may warrant further investigation.

The pharmacokinetics and immunosuppressive response of tacrolimus in paediatric renal transplant recipients.

The aims of our trial were to study the pharmacokinetics of tacrolimus in paediatric kidney transplant recipients. The study comprised 25 patients (median age 13 years, range 2-20 years) followed for 12 months; five pharmacokinetics profiles (within the first and second week and after 1 month, 6 months and 12 months) were obtained. Patients were divided into two groups: six children<6 years old and 19 older children. Tacrolimus was given at an initial dose of 0.15 mg/kg twice a day. Blood samples were drawn before and 1 h, 2 h, 3 h, 4 h, 6 h, 9 h and 12 h after drug administration. Patient and kidney survival rates were 100% at 1 year. At 6 months and 12 months creatinine clearance was 68.5+/-16.3 ml/min per 1.73 m2 and 64.0+/-15.2 ml/min per 1.73 m2 body surface area, respectively. Tacrolimus trough levels were 7.8+/-1.9 ng/ml and 7.3+/-2.5 ng/ml. The area under the concentration-time curve for 0 h to 12 h (AUC0-12) normalised to a dose of 0.15 mg/kg, increased with time from the kidney transplantation and stabilised after the 6th month post-transplantation. During the first month after transplantation the normalised tacrolimus concentration-time profiles were significantly greater in the older children (P<0.05); the actual doses were significantly greater in the younger children (P<0.05). In conclusion, initial doses of 0.15 mg/kg twice a day orally are safe and guarantee a satisfactory degree of immunosuppression, with our therapeutic regimen. Children<6 years old need to start with a 50% higher tacrolimus dose to achieve the same pharmacokinetic and immunosuppressive results.

Childhood thin GBM disease: review of 22 children with family studies and long-term follow-up.

Thin glomerular basement membrane (GBM) disease is generally known to have a good renal prognosis, although renal insufficiency has sometimes been reported and the overlap with Alport syndrome implies that a good prognosis cannot be guaranteed. In order to shed light on long-term prognosis of thin GBM disease we have retrospectively evaluated 22 children with persistent haematuria and biopsy-proven thin GBM. Mean follow up was 7 years (range 2-17 years), mean age at onset was 7 years (range 1.5-15). Biopsies were performed a mean of 3.8 years after detection of hematuria. The light microscopy (LM) and immunofluorescence (IF) findings were essentially unremarkable in all of the children, while electron microscopy (EM) showed thinning of the GBM in all cases and no changes characteristic of Alport syndrome. The family history was positive for renal disease in 17 (77.3%) patients with hematuria in 8 (36.3%) families, and hematuria with renal failure (RF) or deafness in 9 (40.9%). It was completely negative for renal disease in 4 (18.2%) and unavailable in 1 (4.5%). Four patients (18%) showed a decline in renal function after 6, 8, 9 and 12 years of follow-up, and 1 of these also developed hearing impairment. None developed hypertension. Our study suggests that thin GBM disease is not always benign and a child with thin GBM should never be assigned such a prognosis, especially if there is a family history of renal impairment or deafness, where careful follow-up is needed due to the risk of late onset renal failure.

Expression of nuclear transcription factor PAX2 in renal biopsies of juvenile nephronophthisis.

PAX2, a homeotic gene of 'paired box family', is a nuclear transcription factor expressed in mesenchymal/epithelial conversion during the early stages of nephrogenesis; however, its repression is necessary for terminal differentiation of mature tubular cells. Transgenic overexpression in animal model causes epithelial hyperproliferation and microcyst formation. In humans, PAX2 expression has been observed in cystic and dysplasic tubular epithelia in kidney malformation and in kidney disease. We have investigated PAX2 expression and its colocalization with cytokeratin and/or vimentin in 17 biopsies of juvenile nephronophthisis (NPH), an autosomal-recessive renal disease characterized by diffuse renal fibrosis and occasional cysts. Fourteen cases were analyzed for deletion and mutation in the NPH1 gene locus and 33% resulted to be deleted or mutated; for the remaining cases the diagnosis was based on clinical and pathological criteria. The control group included 4 congenital dysplastic kidneys, and 10 biopsies of nephropathies with secondary chronic tubulointerstitial damage. In all cases of renal dysplasia a strong nuclear positivity was observed in immature tubules surrounded by alphaSMA-positive mesenchymal cells. In NI biopsies the tubular epithelia were almost PAX2 negative, although tubulointerstitial damage was severe. In 14/17 NPH1 moderate-to-strong nuclear PAX2 positivity of tubular cells was observed, particularly in cystic distal tubules located at the corticomedullary junction, but also in proximal tubular sections. The PAX2 signal co-localized more with cytokeratin staining than with vimentin. Our results confirm the observation of PAX2 expression in immature dysplastic tubules and its repression in mature renal tubular cells, also in the presence of severe secondary interstitial fibrosis. PAX2 seems to be overexpressed in NPH. The genetic defect of NPH, a disease probably due to a primary defect along the cascade of mesenchymal epithelial differentiation, could generate a functionally abnormal protein involved in focal adhesion signaling and cell/matrix interaction. The failure of PAX2 repression or its reactivation in NPH could be a marker of hyperproliferation and incomplete maturation of epithelial tubular cells, probably due to a defect cell/matrix cross-talk, and involved in interstitial fibrosis and cysts formation.