No clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hypodysplastic nephropathy--report from the ItalKid Project database.

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.

A prospective multicentre study of the nutritional status in children on chronic peritoneal dialysis.

The anthropometry-bioimpedance analysis-nutrition (ABN) score is a recently proposed objective method of assessing malnutrition in children on chronic peritoneal dialysis (CPD) that uses nine parameters based on anthropometry, skinfold thickness and bioimpedance analysis. The aim of this prospective, cross-sectional study was to apply it to children treated with CPD in seven Italian paediatric nephrology centres, with a score of < 10.33 (the 3rd percentile in a population of 264 healthy children) classifying the children as malnourished. The other considered parameters were age, age at the start of dialysis and duration of dialysis; serum haemoglobin, urea, creatinine, total protein, albumin, transferrin, bicarbonate and C-reactive protein; residual urine output; urinary and peritoneal creatinine clearance; and daily protein and energy intake. The study enrolled 43 patients (mean age 10.2 +/- 4.2 years), 21 of whom (48.8%) had an ABN score of < 10.33: 15 with mild, five with moderate, and one with severe malnutrition. The malnourished patients started CPD at a younger age (P < 0.05) and had a longer duration of dialysis (P < 0.01), and a significant worsening in nutritional status was observed in those treated for more than 12 months of dialysis; they also had significantly lower serum albumin, creatinine and haemoglobin levels. In conclusion, protein-calorie malnutrition is common in children receiving CPD. A younger age at the start of dialysis and a longer duration of treatment are clear risk factors, and counterbalance the long-term viability of CPD in paediatric age.

Urea percentiles in children with chronic renal failure. Data from the ItalKid project.

In chronic renal failure high serum urea levels (sUrea) are correlated with the onset of uremic symptoms. Urea has generally been considered relatively non-toxic, functioning more as a surrogate for other toxic solutes; however, it has been recently reported that it can contribute to uremic toxicity. Clinically sUrea are often difficult to interpret because of the wide range of kidney functions. To obtain a practical and easily accessible tool to evaluate sUrea, we have produced percentile curves for different ranges of chronic renal failure, defined with creatinine clearance ( C(Cr)) obtained with the Schwartz formula. Data were obtained from the Italian Pediatric Registry of Chronic Renal Failure (ItalKid); its inclusion criteria are: (1) C(Cr )<75 ml/min per 1.73 m(2), (2) age <20 years at time of registration, and (3) conservative treatment. To obtain the percentiles, the following patients were excluded: patients with an underlying disease, a concomitant treatment, or a disorder that could affect urea metabolism, per se, and/or food intake, and patients aged <2 years. The study group included 690 subjects (mean age 9.56+/-4.54 years, 485 males). In total, 2,085 observations (C(Cr )and sUrea) were available for the construction of the percentile curves. A median of 258 (range 99-380) observations was obtained for each of the eight different categories of C(Cr )(intervals of 10 ml/min per 1.73 m(2)). The 10th, 25th, 50th, 75th, and 90th percentiles were calculated and a graph was produced. Patients with the highest urea percentiles showed significantly higher plasma levels of phosphorus and parathyroid hormone and significantly lower hemoglobin concentrations and bicarbonate levels. Our percentile curves may help to identify subjects with inappropriate sUrea for a given C(Cr).

Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy. Data from the Ital Kid Project.

Little is known about the role of proteinuria in the progression of childhood renal diseases. We analyzed the decline in creatinine clearance ( C(Cr)) and kidney survival in 225 children (185 males) with chronic renal failure (CRF) due to isolated hypodysplasia or hypodysplasia associated with urological abnormalities. The data were based on the information available in the Italian Pediatric Registry of CRF (ItalKid Project), which includes patients from all of Italy aged <20 years with C(Cr )levels of <75 ml/min per 1.73 m(2). Patients aged <2 years and those with C(Cr )levels of <20 ml/min per 1.73 m(2) or a follow-up of <1 year were excluded from the analysis, as were those receiving angiotensin-converting enzyme inhibitors. At baseline, the patients had a mean age of 7.8+/-4.2 years, a mean C(Cr )of 50+/-16.3 ml/min per 1.73 m(2), a median urinary protein/urinary creatinine (uPr/uCr) ratio of 0.38 (range 0.02-7.21), and a mean duration of follow-up of 3.5+/-1.1 years. The patients were divided into three groups on the basis of their baseline proteinuria levels: group A normal (uPr/uCr <0.2) n=83; group B low (uPr/uCr 0.2-0.9) n=71; and group C mild (uPr/uCr >0.9) n=71. Patients in groups A and B showed a significantly slower decline in C(Cr )than those in group C (slope +0.16+/-3.64 and -0.54+/-3.67 vs. -3.61+/-5.47, P<0.0001) and a higher rate of kidney survival after 5 years (96.7% and 94.1% vs. 44.9%, P<0.01). By multivariate analysis, the baseline uPr/uCr ratio ( P<0.01) and age ( P<0.0001) correlated with a faster decline in C(Cr )irrespective of baseline C(Cr). There was no correlation with mean arterial blood pressure. We conclude that proteinuria is an independent predictor of progression to end-stage renal failure also in children whose renal impairment is due to congenital hypodysplasia.

Long-term outcome of vesicoureteral reflux associated chronic renal failure in children. Data from the ItalKid Project.

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.