[Apheresis in children: procedures and outcome]. / Aferesi in eta' pediatrica: procedure e outcome.

Apheresis procedures are used in children to treat an increasing number of conditions by removing different types of substances from the bloodstream. In a previous study we evaluated the first results of our experience in children, emphasizing the solutions adopted to overcome technical difficulties and to adapt adult apheresis procedures to a pediatric population. The aim of the present study is to present data on a larger number of patients in whom apheresis was the main treatment. Ninety-three children (50 m, 43 f) affected by renal and/or extrarenal diseases were included. They were treated with LDL apheresis, protein A immunoadsorption, or plasma exchange. Our therapeutic protocol was the same as described in the previous study. Renal diseases and immunological disorders remained the most common conditions requiring this therapeutic approach. However, hemolytic uremic syndrome (HUS) was no longer the most frequent renal condition to be treated, as apheresis is currently the first treatment option only in cases of atypical HUS. In this series we also treated small children, showing that low weight should no longer be considered a contraindication to apheresis procedures. The low rate of complications and the overall satisfactory clinical results with increasingly advanced technical procedures make a wider use of apheresis in children realistic in the years to come.

Peritoneal dialysis in infants: the experience of the Italian Registry of Paediatric Chronic Dialysis.

BACKGROUND: Although chronic peritoneal dialysis (CPD) is considered the replacement therapy of choice for infants with end-stage renal failure, many questions persist about treatment risks and outcomes. METHODS: We present data on 84 infants who started CPD at <1 year of age; these patients represent 12% of the total population of the Italian Registry of Paediatric Chronic Dialysis. We analysed patient records from all children consecutively treated with CPD between 1995 and 2007 in Italy. Growth data analysis was performed only in infants with complete auxological parameters at 0, 6 and 12 months of follow-up. RESULTS: Median age at the start of CPD was 6.9 months, weight was 6.1 kg and length 63.6 cm. In one-half of the study population diagnosis leading to renal failure was congenital nephrouropathy. Twenty-eight per cent of the children had at least one pre-existing comorbidity. The mean height standard deviation score was -1.65 at the start of CPD, -1.82 after 12 months and -1.53 after 24 months. Catch-up growth was documented in 50% of patients during dialysis. A positive correlation was observed between longitudinal growth and both exchange volume (R(2) = 0.36) and dialysis session length (R(2) = 0.35), while a negative association was found with the number of peritonitis cases (P = 0.003). Peritonitis incidence was 1:20.7 episode:CPD-months (1:28.3 in the older children from the same registry) and was significantly higher in children with oligoanuria (1:15.5 episode:CPD-months) compared to infants with residual renal function (1:37.4 episode:CPD-months). Catheter survival rate was 70% at 12 months and 51% at 24 months. Catheter-related complications were similar in infants and older children (1:20.5 versus 1:19.8 episode:CPD-months), while clinical complications were more frequent in children under 1 year of age (1:18.3 versus 1:25.2 episode:CPD-months; P < 0.05). During the follow-up period, 33 patients were transplanted (39.3%), 18 were shifted to haemodialysis (21.4%) and 8 died (9.5%). The mortality rate was 4-fold greater than in older children (2.3%). CONCLUSIONS: Our data confirm that infants on CPD represent a high-risk group; however, our experience demonstrated that growth was acceptable and a large portion was successfully transplanted. Increased efforts should be aimed at optimizing dialysis efficiency and preventing peritonitis. The higher mortality rate in infants was largely caused by comorbidities.

Effect of carnitine supplementation on lipid profile and anemia in children on chronic dialysis.

We prospectively evaluated the effects of L-carnitine supplementation on plasma free carnitine (FC) levels, serum lipid profile, and erythropoietin (rhEPO) requirement in 24 children treated with peritoneal dialysis (PD; n=16) or hemodialysis (HD; n=8). The study was divided into a 3-month observation period, and a 3-month treatment period during which patients received 20 mg/kg per day of L-carnitine given orally. Clinical, biochemical, and hematological data were collected every 3 months. FC levels were measured in plasma and peritoneal dialysate by tandem mass spectrometry. There were no statistically significant changes in lipid levels, hemoglobin, or rhEPO requirements during the course of the study. Fifteen patients (13 PD, 2 HD) had plasma FC levels measured before and after treatment; FC levels increased from 32.1 +/- 14.1 micromol/l to 80.9 +/- 38.7 micromol/l (P<0.001). In PD patients, dialysate FC losses increased from 106 +/- 78 micromol/day at baseline to 178 +/- 119 micromol/day after supplementation. Positive correlations between FC plasma levels and dialysate levels (R=0.507) or daily excretion (R=0.603) were found after treatment. In our case series, an oral dose of 20 mg/kg per day of L-carnitine restored FC levels and produced a positive carnitine balance with no significant effects on hematological parameters or lipid profile over a 3-month period. Prolonged treatment duration may be required to obtain significant results.

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.

Chronic peritoneal dialysis catheters in children: a fifteen-year experience of the Italian Registry of Pediatric Chronic Peritoneal Dialysis.

OBJECTIVE: To analyze data on 503 chronic peritoneal dialysis (CPD) catheters implanted between 1986 and 2000 in pediatric patients enrolled in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (the Registry), comparing three different time periods: 1986-1990, 1991-1995, and 1996-2000. DESIGN: Retrospective study. SETTING: 23 dialysis centers participating in the Registry. METHODS: Data were collected from questionnaires filled in every year. The information for each peritoneal catheter included type, site and technique of insertion, exit-site orientation, exit-site care, complications, survival, and reason for removal. PATIENTS: 503 catheters were implanted in 363 pediatric patients aged younger than 15 years at the start of CPD: 97 catheters in patients under 2 years of age, 67 in patients aged 2-5 years, and 339 in patients over 5 years of age. Mean patient age at onset of CPD was 8.0 +/- 5.1 years. All catheters were surgically implanted and omentectomy was performed in 82.4% of cases. The catheters used were Tenckhoff [468 (93.0%): 443 double cuff, 25 single cuff] and double-cuffed Valli [35 (7.0%)]. The entry site was in the midline in 153 cases (30.4%) and paramedian in 350 (69.6%). RESULTS: During 9048 dialysis-months we observed 451 catheter-related complications, yielding an incidence of 1 episode/20.1 CPD-months: 330 catheter infections (exit-site and/or tunnel infections), 26 leakages, 26 dislocations, 24 obstructions, 22 cuff extrusions, 6 hemoperitoneums, 17 others. 171 catheters were removed due to catheter-related causes; exit-site and/or tunnel infections were the main cause for removal (75.4%), followed by obstruction, dislocation, outer-cuff extrusion, and leakage. Younger children (< 2 years) had a higher risk of infectious causes of catheter removal compared to children aged 2-5 years (p = 0.004) and over 5 years of age (p = 0.002). During the 15-year observation period, a significant reduction in the incidence of leakage was observed and risk of leakage was lower in catheters with paramedian entry site compared to catheters with midline entry site. Removal and replacement of peritoneal catheters during the same surgical operation was performed in 76.3% of catheter removals. Catheter survival rate was 78.1% at 12 months, 58.5% at 24 months, 43.8% at 36 months, and 34.6% at 48 months. No difference in catheter survival was observed in younger children (< 2 years) compared with the two other age groups: < 2 years versus 2-5 years hazard ratio 0.7, 95% confidence interval (95%CI) 0.4-1.2; < 2 years versus > 5 years hazard ratio 0.8, 95%CI 0.5-1.1. CONCLUSIONS: In this survey, we observed better catheter survival in comparison with data reported by the Registry in 1998. Catheter survival improved especially in younger children (< 2 years), a group that previously had a decreased catheter survival rate compared to older age groups. In addition to the progressive increase in experience acquired by dialysis centers, this upward trend may also be related to greater use of double-cuffed catheters, with paramedian exit site, and a higher frequency of omentectomy.

A multicenter experience on patient and technique survival in children on chronic dialysis.

In this study we compared patient and technique survival of 163 new hemodialysis (HD) patients (age 11.4+/-3.1 years) and 295 peritoneal dialysis patients (7.7+/-4.8 years. P< 0.001), treated in 23 dialysis centers participating in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) during the years 1989-2000. Three HD (1.8%) and 17 CPD (5.8%) patients died; the overall average death rate was 9.8/1,000 patient-years in HD and 29.8/1,000 patient-years in CPD patients. No statistically significant difference in patient survival between CPD and HD was found, while the survival of 102 CPD children younger than 5 years at the start of dialysis was lower ( P=0.0001) than that of 193 CPD and 160 HD patients aged 5-15 years. We registered 12 modality failures among HD (7.4%) patients and 44 among CPD (14.9%) patients. The main causes were vascular access failure and patient choice in HD, and infection in CPD patients. Technique survival was lower ( P=0.007) in CPD than in HD patients; a statistically significant difference ( P=0.01) was also observed between both the 0- to 5- and the 5- to 15-year-old CPD patients and the HD patients aged 5-15 years. Logistic regression analysis confirmed age at initiation of dialysis to be a predictor of patient death ( P=0.0001) in the whole patient population, and of technique failure in HD ( P=0.006) but not in CPD patients ( P=0.16).

Middle molecule and small protein removal in children on peritoneal dialysis.

BACKGROUND: Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the contribution of residual renal function in peritoneal dialysis (PD) children. METHODS: Seventeen patients of 12 +/- 4 years undergoing automated PD were studied. Ten patients had 563 +/- 355 mL/day of urine output, and 7 were anuric. During a standardized nightly intermittent PD (NIPD) session, a single-injection inulin clearance was performed. Urea, creatinine, inulin (measured by HPLC), cystatin C and beta2-microglobulin (beta2m) were measured in blood, urine and dialysate. Clearances (L/week/1.73 m2) and weekly solute removal index (SRI) were calculated for all the solutes; weekly Kt/V was calculated for urea. RESULTS: In non-anuric versus anuric patients the total clearances were: urea 82.6 +/- 18.3 versus 71.3 +/- 26.4; creatinine 82.7 +/- 28.6 versus 47.8 +/- 18.8; inulin 42.8 +/- 11.3 versus 32.8 +/- 20.4; beta2m 14.2 +/- 13.8 versus 9.2 +/- 8.3; cystatin C 20.2 +/- 9.4 versus 9.7 +/- 4.8. In the patients with residual diuresis, the urea was removed mainly by PD (69.2%), while inulin, beta2m and cystatin C were removed by renal clearance (64.0%, 79.5% and 62.8%, respectively). Total, peritoneal and renal weekly Kt/V values in the subjects with residual renal function, were 2.86 +/- 0.70, 1.99 +/- 0.40 and 0.87 +/- 0.43, respectively. Peritoneal weekly Kt/V in the anuric patients was 2.36 +/- 0.85; total weekly Kt/V in the total group was 2.65 +/- 0.78. Weekly SRIs in non-anuric versus anuric patients were: urea 2.56 +/- 0.58 versus 2.09 +/- 0.74; creatinine 2.66 +/- 0.73 versus 1.46 +/- 0.56; inulin 2.36 +/- 0.92 versus 1.64 +/- 1.60; beta2m 1.26 +/- 1.10 versus 1.20 +/- 1.90; cystatin C 1.72 +/- 0.83 versus 1.58 +/- 1.62. CONCLUSIONS: Solutes removed during PD tend to decrease following an increase in molecular weight of the substance. Since anuric patients are at higher risk of middle molecule and small protein accumulation, more attention should be paid to the removal of middle molecules. Further studies should be undertaken to evaluate whether removing them has a clinical impact and to determine their threshold levels.