Sara Viganò

PURPOSE: The nephropathy associated with vesicoureteral reflux (VUR) is one of the leading causes of chronic renal failure (CRF) in children. We describe the clinical course of the disease based on information available in the ItalKid Project database, and analyze the predictive value of baseline renal function, age at VUR diagnosis and urinary protein excretion in relation to the risk of progressive renal failure. MATERIALS AND METHODS: As of December 31, 2001 the registry included a total of 343 patients (261 males) with a diagnosis of primary VUR, which was the leading single cause of CRF, accounting for 25.4% of all patients with CRF. RESULTS: The estimated risk of end stage renal disease (ESRD) by age 20 years was 56%. The patients with a creatinine clearance (Ccr) of less than 40 ml per minute at baseline had an estimated 4-fold greater risk of ESRD developing in comparison with those whose Ccr was 40 to 75 ml per minute. No significant difference in probability of disease progression to ESRD was found between subjects diagnosed with VUR at age 6 months or less and those diagnosed later (older than 6 months). Furthermore, children with normal urinary protein excretion (a urinary protein [uPr]/urinary creatinine [uCr] ratio of less than 0.2 in 36 patients) and low grade proteinuria (uPr/uCr 0.2 to 0.8 in 34 patients) at baseline showed a significantly slower decrease in mean Ccr than those with moderate proteinuria (uPr/uCr greater than 0.8 in 34 patients). Hypertension and/or antihypertensive treatment (including antiprogressive drugs) were reported in 29.1% of patients. CONCLUSIONS: The results of the present study define the long-term risk of ESRD in a large population of children with CRF and VUR, and provide some critical information for identifying the prognosis.

OBJECTIVE: To analyse the timing of end stage renal disease in children with chronic kidney disease (CKD). DESIGN: A population-based cohort study. SETTING: A nationwide registry (ItalKid Project) collecting information on all patients with CKD aged <20 years. PATIENTS: 935 children with CKD secondary to renal hypodysplasia with or without urologic malformation. In a subgroup of patients (n=40) detailed pubertal staging was analysed in relation to CKD progression. MAIN OUTCOME MEASURES: Kidney survival (KS) was estimated using renal replacement therapy (RRT) as the end-point. Puberty was staged by identifying the pubertal growth spurt. RESULTS: A non-linear decline in the probability of KS was observed, with a steep decrease during puberty: the probability of RRT was estimated to be 9.4% and 51.8% during the first and second decades of life, respectively. A break-point in the KS curve was identified at 11.6 and 10.9 years of age in male and female patients, respectively. CONCLUSIONS: The present analysis suggests that puberty is associated with increased deterioration of renal function in CKD. The mechanism(s) underlying this unique and specific (to children) pattern of progression have not yet been identified, but it may be that sex hormones play a role in this puberty-related progression of CKD.

BACKGROUND: Chronic kidney diseases (CKD) tend to progress to end-stage renal failure (ESRF). As it has been demonstrated that angiotensin-converting enzyme inhibitors (ACEi) have a renoprotective effect in adults with proteinuric disease and may be effective in reducing hyperfiltration and proteinuria, they are also frequently used as anti-progression agents in paediatric patients with CKD despite the lack of data confirming their role in the nephropathies peculiar to children. The aim of this study was to investigate whether patients with hypodysplastic CKD (the most common cause of ESRF in children) treated with ACEi show a significantly slower decline in creatinine clearance (Ccr). METHODS: The analysis was based on the information available in the database of the ItalKid Project, a nationwide, population-based registry of chronic renal insufficiency (CRI) in children in Italy. Of the 822 patients with CRI due to hypodysplasia, we selected those who had been continuously treated with ACEi; the control patients were identified from the same diagnostic group and matched for gender, age and baseline Ccr. RESULTS: Progression was analysed as the slope of Ccr in a total of 164 patients: 41 cases and 123 matched controls. There were no significant between-group differences in blood pressure, duration of follow-up or pre-study slope of Ccr (-0.31+/-2.26 vs -0.33+/-3.58 ml/min/1.73 m2/year; P=NS). After an average of 4.9+/-2.3 years, the mean slope of Ccr was 40% lower in the ACEi-treated cases in comparison to controls (-1.08+/-2.08 vs -1.80+/-4.42 ml/min/1.73 m2/year), however, this difference was not statistically significant (P=0.31). CONCLUSIONS: We conclude that ACEi treatment does not significantly modify the naturally progressive course of hypodysplastic nephropathy in children and further studies are necessary before such treatment is routinely proposed for anti-progression purposes in children with CKD.