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Background: Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis., Methods: Patients < 18 years old on hemodialysis (HD) or peritoneal dialysis (PD) in six European Pediatric Dialysis Working Group centers were recruited. sNaB was calculated from enteral Na, obtained by a 3-day diet diary, Na intake from medications, and 24-h urinary Na (uNa). Primary outcomes were systolic blood pressure and diastolic blood pressure standard deviation scores (SBP and DBP SDS), obtained by 24-h ambulatory blood pressure monitoring or office BP according to age, and interdialytic weight gain (IDWG)., Results: Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3%) received Na-containing drugs, accounting for 0.6 (0.7) mEq/kg/day. Median total Na intake was 1.5 (1.1) mEq/kg/day, corresponding to 60.6% of the maximum recommended daily intake for healthy children. Median uNa and sNaB were 0.6 (1.8) mEq/kg/day and 0.9 (1.7) mEq/kg/day, respectively. The strongest independent predictor of sNaB in the cohort was urine output. In patients receiving HD, sNaB correlated with IDWG, pre-HD DBP, and first-hour refill index, a volume index based on blood volume monitoring. sNaB was the strongest predictor of IDWG in multiple regression analysis (β = 0.63; p = 0.005). Neither SBP SDS nor DBP SDS correlated with sNaB., Conclusions: Na intake is higher than uNa in children on dialysis, and medications may be an important source of Na. sNaB is best predicted by urine output in the population, and it is a significant independent predictor of IDWG in children on HD. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Previous studies investigating hospitalizations in dialysis patients have focused primarily on patient-centered factors. We analyzed the impact of hospital and dialysis unit characteristics on pediatric dialysis patients' hospitalizations for access-related complications (ARCs)., Methods: This cross-sectional study involved 102 hemodialysis (HD) and 163 peritoneal dialysis (PD) patients. Data between July 2017 and July 2018 were analyzed., Results: Children's hospitals (CHs) had more pediatric nephrologists and longer PD experience (years) than general hospitals (GHs) (p = 0.026 and p = 0.023, respectively). A total of 53% of automated PD (APD) and 6% of continuous ambulatory PD (CAPD) patients were in CHs (p < 0.001). Ninety-three percent of APD and 69% of CAPD patients were treated in pediatric-specific PD units (p = 0.001). CHs had a higher prevalence in providing hemodiafiltration (HDF) than GHs (83% vs. 30%). Ninety-seven percent of HDF vs. 66% for conventional HD (cHD) patients, and 94% of patients with arteriovenous fistula (AVF) vs. 70% of those with central venous catheters (CVC), were dialyzed in pediatric-specific HD units (p = 0.001 and p = 0.016, respectively). Eighty patients (51 PD and 29 HD) had 135 (84 PD, 51 HD) hospitalizations. CAPD was an independent risk factor for hospitalizations for infectious ARCs (I-ARCs) (p = 0.009), and a health center's PD experience negatively correlated with CAPD patient hospitalizations for I-ARCs (p = 0.041). cHD and dialyzing in combined HD units significantly increased hospitalization risk for non-infectious (NI-)ARCs (p = 0.044 and p = 0.017, respectively)., Conclusions: CHs and pediatric-specific dialysis units have higher prevalence of APD and HDF use. Hospitalizations for I-ARCs in CAPD are lower in centers with longer PD experience, and pediatric HD units are associated with fewer hospitalizations due to NI-ARCs. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Sociocultural issues play a key role in children needing kidney replacement therapy (KRT)., Methods: Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ("resident foreign patients," RFPs) and those from native parents ("domestic patients," DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2)., Results: We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups., Conclusions: The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups. Graphical abstract.

Background: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic., Methods: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics., Results: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines., Conclusions: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists' response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US.

Background: High volume haemodiafiltration (HDF) is associated with better survival than conventional haemodialysis (HD) in adults, but data concerning its use in children are lacking. The aim of this study was to assess the prevalence of paediatric HDF use and its associated factors in recent years in Italy., Methods: We retrospectively reviewed the files of patients from the Italian Pediatric Dialysis Registry's database who were registered between January 1, 2004 and December 31, 2016 and treated with extracorporeal dialysis for at least 6 months, looking in particular at modality and its associated factors., Results: One hundred forty-one out of 198 patients were treated exclusively with bicarbonate HD (71.2%), 57 with HDF (28.8%). Patients treated with HDF were younger (median 9.7 vs 13.2 years, p = 0.0008), were less often incident patients (52.6% vs 75.9%, p = 0.0031), had longer duration of the HD cycle (26.9 vs 20.8 months, p = 0.0036) and had a longer time to renal transplantation (32 vs 25 months, p = 0.0029) than those treated with bicarbonate HD only. The percentage of patients treated with HDF increased with dialysis vintage (16.9% at 6 months, 38.1% after more than 2 years of dialysis). The use of HDF was stable over time and was more common in the largest centres., Conclusions: Over the observation period, HDF use in Italy has been limited to roughly a quarter of patients on extracorporeal dialysis, in particular to those with high dialysis vintage, younger age or a long expected waiting time to renal transplantation.

Background: Children with congenital nephrotic syndrome (CNS) commonly develop end stage renal failure in infancy and require dialysis, but little is known about the complications and outcomes of dialysis in these children., Methods: We conducted a retrospective case note review across members of the European Society for Pediatric Nephrology Dialysis Working Group to evaluate dialysis management, complications of dialysis, and outcomes in children with CNS., Results: Eighty children (50% male) with CNS were identified form 17 centers over a 6-year period. Chronic dialysis was started in 44 (55%) children at a median age of 8 (interquartile range 4-14) months. Of these, 17 (39%) were on dialysis by the age of 6 months, 30 (68%) by 1 year, and 40 (91%) by 2 years. Peritoneal dialysis (PD) was the modality of choice in 93%, but 34% switched to hemodialysis (HD), largely due to catheter malfunction (n = 5) or peritonitis (n = 4). The peritonitis rate was 0.77 per patient-year. Weight and height SDS remained static after 6 months on dialysis. In the overall cohort, at final follow-up, 29 children were transplanted, 18 were still on dialysis (15 PD, 3 HD), 19 were in pre-dialysis chronic kidney disease (CKD), and there were 14 deaths (8 on dialysis). Median time on chronic dialysis until transplantation was 9 (6-18) months, and the median age at transplantation was 22 (14-28) months., Conclusions: Infants with CNS on dialysis have a comparable mortality, peritonitis rate, growth, and time to transplantation as infants with other primary renal diseases reported in international registry data.

Background: Volume overload is a known risk factor for cardiovascular complications in children on hemodialysis (HD), but a measurable index of volume overload is still lacking., Methods: We propose a novel index of pre-HD volume overload based on blood volume (BV) monitoring, the first hour refill index (RI), calculated as the ratio between the ultrafiltration rate indexed for body weight during the first HD hour and the percent BV change at the first hour of the treatment. This parameter was retrospectively calculated in 121 sessions in 11 oligoanuric children and young adults on chronic HD, with median age 14.3 years (range 5.4-22.4), and its association with left-ventricular mass index, pre-HD blood pressure, and number of antihypertensive medications was evaluated., Results: The median RI was 2.07 ml/kg/h/%. There was a significant correlation between RI and median LVMI (r 0.66, p = 0.028), which was 53.4 g/m 2.7 (45.7-64) in patients with a median RI > 2, and 36.6 g/m 2.7 (24.9-47) in those with a median RI < 2 ml/kg/h/% (p = 0.01). The number of antihypertensive drugs per patient was significantly higher in patients with a RI > 2 than in those with a RI < 2 ml/kg/h/% (three vs one per patient; p = 0.02) while blood pressure was not significantly different between the two groups., Conclusions: The ratio between the ultrafiltration rate per body weight and the BV change during the first hour of a HD session could be a promising index of refill capacity and pre-HD volume overload in children and young adults on chronic HD.

Background: Impairment in orexigenic/anorexigenic hormone balance may be key in the pathogenesis of protein energy wasting in children with chronic kidney disease (CKD). Measurement of ghrelin and obestatin concentrations in children with CKD would help assess the potential contribution of these hormones to uremic protein energy wasting., Methods: This was a cross-sectional case-control study. Acylated and unacylated ghrelin and obestatin were measured in 42 children on conservative treatment (CT), 20 children on hemodialysis, 48 pediatric renal transplant (RTx) recipients and 43 controls (CTR) (mean age 11.9, range 5-20 years). Weight, height and bicipital, tricipital, subscapular and suprailiac folds were measured, and the body mass index-standard deviation score (BMI-SDS), percentage of fat mass and fat-free mass were calculated. Urea and creatinine were measured and the glomerular filtration rate (GFR) calculated., Results: Unacylated ghrelin level was higher in patients than controls (p = 0.0001), with the highest levels found in hemodialysis patients (p = 0.001 vs. CKD-CT, p = 0.0001 vs. RTx, p < 0.0001 vs. CTR). Obestatin level was significantly higher in patients on hemodialysis than those on conservative treatment, RTx recipients and controls (p < 0.0001 in each case). Unacylated ghrelin negatively correlated with weight-SDS (p < 0.0001), BMI-SDS (p = 0.0005) and percentage fat mass (p = 0.004) and positively correlated with percentage fat-free mass (p = 0.004). Obestatin concentration negatively correlated with weight-SDS (p = 0.007). Unacylated ghrelin and obestatin concentrations positively correlated with creatinine and urea and inversely with eGFR, even after adjustments for gender, age, puberty and BMI-SDS (p < 0.0001 for each model)., Conclusions: Unacylated ghrelin and obestatin, negatively related to renal function, seem to be promising inverse indicators of nutritional status in children with CKD. Potential therapeutic implications in terms of optimization of their removal in patients on hemodialysis could be hypothesized.

Background: Chronic haemodialysis (HD) in small children has not been adequately investigated., Methods: This was a retrospective investigation of the use of chronic HD in 21 children aged  <2 years (n = 12 aged <1 year) who were registered in the Italian Pediatric Dialysis Registry. Data collected over a period of >10 years were analysed., Results: The median age of the 21 children at start of HD was 11.4 [interquartile range (IQR) 6.2-14.6] months, and HD consisted mainly of haemodiafiltration for 3-4 h in  ≥4 sessions/week. A total of 51 central venous catheters were placed, and the median survival of tunnelled and temporary lines was 349 and 31 days, respectively (p  < 0.001). Eight children (38 %) showed evidence of central vein thrombosis. Although 19 % of patients received growth hormone and 63.6 % received enteral feeding, the weight and height of these patients remained suboptimal. During the HD period the haemoglobin level increased in all patients, but not to normal levels (from 8.5 to 9.6 g/dl) despite erythropoietin administration (503-600 U/kg/week). The hospitalisation rate was 1.94/patient-year. Seventeen patients underwent renal transplantation at a median age of 3.0 years. Four patients, all affected by severe comorbidities, died during follow-up (in 2 cases due to absence of a vascular access). The 5- and 10-year cumulative survival was 82.4 and 68.7 %, respectively., Conclusions: Extracorporeal dialysis is feasible in children aged  <2 years, but comorbidities, vascular access, growth and anaemia remain major concerns.

Background: To date, no study has investigated the use of vitamin K antagonists (VKA) in children undergoing chronic haemodialysis (HD) with a central venous catheter (CVC)., Methods: Consecutive patients aged <18 years with a newly placed tunnelled CVC for chronic HD were enrolled over a 3-year period. Children with active nephrotic syndrome or a history of venous thrombosis received warfarin (VKA group) with therapeutic target international normalised ratios of between 2.0 and 3.0. Patients at standard risk of CVC malfunction were not treated with VKA (standard group). The primary end-point was overall CVC survival., Results: The VKA group consisted of nine patients (median age 10.6 years; range 1.2-15.3 years) with 11 CVC, and the standard group comprised eight patients (11.8 years; 6.1-17.3 years) with ten CVC. The 6- and 12-month CVC survival was significantly longer in the VKA group than in the standard group (100 vs. 60 % and 83.3 vs. 16.7 %, respectively; p < 0.05), with a median survival of 369 and 195 days, respectively (p < 0.05). None of the CVC in the VKA group required removal due to malfunction, as compared to four in the standard group. No major bleeding episodes occurred in either group., Conclusions: Therapy with VKA would appear to be safe in children on chronic HD and may improve CVC survival in patients at increased risk of CVC thrombosis.

Background: Hemodialysis (HD) in children with a concomitant ventriculoperitoneal shunt (VPS) is rare. Registry data suggest that peritoneal dialysis with a VPS is safe, but little is known about HD in the presence of a VPS., Methods: We performed a 10-year survey to determine the prevalence of a VPS, complications and outcome in children with a VPS on HD in 15 dialysis units from the 13 countries participating in the European Pediatric Dialysis Working Group., Results: Eleven cases of HD with a VPS were reported (prevalence 1.33 %; 328 patient-months) and compared with prospective Registry data. The median age at start of dialysis was 9.6 [inter-quartile range (IQR) 1.0-15.0] years and median HD vintage was 2.4 (IQR 1.7-3.0) years. Dialysis was performed through a central venous line (CVL) and through an arteriovenous fistula in six and five children, respectively. Three CVL infections occurred in two children, but these children did not develop VPS infections or meningitis. Symptoms of hemodynamic instability were reported in six (55 %) children at least once per week, with hypotension or hypertension occurring in four of these children and nausea, vomiting and headaches occurring in two; four other children reported less frequent symptoms. Seizures on dialysis occurred in two children, at a frequency of less than once per month, with one child also experiencing visual disturbances. During follow-up (median 4.0; IQR 0.38-7.63 years), three children remained on HD and eight had a functioning transplant. No patients were switched to PD., Conclusions: Hemodialysis in children with a VPS is safe, but associated with frequent symptoms of hemodynamic instability. No episodes of VPS infection or meningitis were seen among the children in the survey, not even in those with CVL sepsis.

Background: Pleural or pericardial effusions secondary to pleuro-peritoneal fistula (PPF) and pericardio-peritoneal fistula (PcPF) are rare but serious complications of peritoneal dialysis (PD)., Methods: We conducted a 10-year survey across all participating centres in the European Paediatric Dialysis Working Group to review the incidence, diagnostic techniques, therapeutic options and outcome of children on chronic PD with PPF and/or PcPF., Results: Of 1506 children on PD there were ten cases (8 of PPF, 1 each of PcPF and PPF + PcPF), with a prevalence of 0.66%. The median age at presentation was 1.5 [inter-quartile range (IQR) 0.4-2.4] years, and nine children were <3 years. The time on PD before onset of symptoms was 4.3 (IQR 1.3-19.8) months. Eight children had herniae and seven had abdominal surgery in the preceding 4 weeks. Symptoms at presentation were respiratory distress, reduced ultrafiltration and tachycardia. PD was stopped in all children; three were managed conservatively and thoracocentesis was performed in seven (with pleurodesis in 3). PD was restarted in only three children, in two of them with success., Conclusion: In conclusion, PPF and PcPF are rare in children on chronic PD, but are associated with significant morbidity, requiring a change of dialysis modality in all cases. Risk factors for PPF development include age of <3 years, herniae and recent abdominal surgery.

Background: Little is known about the clinical impact of interdialytic weight gain (IDWG) on oligoanuric children undergoing chronic hemodialysis (HD)., Methods: We retrospectively assessed IDWG, left ventricular mass index (LVMI) and its changes (ΔLVMI), pre-HD systolic and diastolic blood pressure (DBP), residual urine output, Kt/V, the frequency of intradialytic symptoms, normalized protein catabolic rate, and the 3-month change in the dry weight of 16 hemodialyzed oligoanuric patients with a median age of 14.8 years (range 5.0-17.9)., Results: There was a significant correlation between IDWG and median LVMI (r 0.55, p = 0.026), which was 27.3 g/m(2.7) (22.5-37.6) in the patients with a median IDWG of <4 %, and 44.3 g/m(2.7) (28.2-68.7) in those with a median IDWG of >4 % (p = 0.003). None of the four patients with an IDWG of <4 % showed left ventricular hypertrophy, compared with 10 of the 12 patients (83.3 %) with an IDWG of >4 % (p = 0.003); the former also had a better median ΔLVMI (-33.5 % vs -13.0 %; p = 0.02) and a lower median DBP sds (0.24 vs 1.72, p = 0.04)., Conclusions: There is a significant correlation between IDWG and LVMI in pediatric oligoanuric patients on chronic HD: those with an IDWG of >4 % are at a higher risk of left ventricular hypertrophy.

Background: The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol, Methods: This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to <15 years who presented with onset of nephrotic syndrome to 54 pediatric units and six pediatric nephrology units in Italy between 2007 and 2009 were eligible for entry into the study., Results: Median steroid dosing was 55 (range 27-75) mg/m(2)/day. The overall median cumulative dose regimen for the first episode was 3,440 (1,904-6,035) mg/m(2), and the median duration of the therapeutic regimen was 21 (9-48) weeks. The total duration and cumulative steroid dose were significantly higher in patients treated by pediatricians than in those treated by pediatric nephrologists (p = 0.001 and p = 0.008). Among the patient cohort, 55, 64 and 22 % received albumin infusions, diuretics and acetyl salicylic acid treatment, respectively, but the laboratory and clinical data did not differ between children treated or not treated with symptomatic drugs. Albumin and diuretic use did not vary between patients in pediatric units and those in pediatric nephrology units., Conclusions: This study shows major differences in steroid and symptomatic treatment of nephrotic syndrome by pediatricians and pediatric nephrologists. As these differences can influence the efficacy of the treatments and the appearance of side-effects, shared guidelines and their implementation through widespread educational activities are necessary.

Background: Few observations on apheresis in pediatric nephrology units have been published., Methods: This retrospective study involved children ≤18 years undergoing plasma exchange (PE), immunoadsorption (IA), or double filtration plasmapheresis (DFPP) in 12 European pediatric nephrology units during 2012., Results: Sixty-seven children underwent PE, ten IA, and three DFPP, for a total of 738 PE and 349 IA/DFPP sessions; 67.2 % of PE and 69.2 % of IA/DFPP patients were treated for renal diseases, in particular focal segmental glomerulosclerosis (FSGS), hemolytic-uremic syndrome (HUS), and human leukocyte antigen (HLA) desensitization prior to renal transplantation; 20.9 % of PE and 23.1 % of IA/DFPP patients had neurological diseases. Membrane filtration was the most common technique, albumin the most frequently used substitution fluid, and heparin the preferred anticoagulant. PE achieved full disease remission in 25 patients (37.3 %), partial remission in 22 (32.8 %), and had no effect in 20 (29.9 %). The response to IA/DFPP was complete in seven patients (53.8 %), partial in five (38.5 %), and absent in one (7.7 %). Minor adverse events occurred during 6.9 % of PE and 9.7 % of IA/DFPP sessions., Conclusions: PE, IA, and DFPP are safe apheresis methods in children. Efficacy is high in pediatric patients with recurrent focal segmental glomerulosclerosis (FSGS), atypical hemolytic uremic syndrome (HUS), human leukocyte antigen (HLA) sensitization, and neurological autoimmune diseases.

Background: There is increasing focus on the problems involved in the transition and transfer of young adult patients from paediatric to adult renal units. This situation was addressed by the 2011 International Pediatric Nephrology Association/International Society of Nephrology (IPNA/ISN) Consensus Statement on transition., Methods: We performed a survey of transition practices of 15 paediatric nephrology units across Europe 2 years after publication of the consensus statement., Results: Two thirds of units were aware of the guidelines, and one third had integrated them into their transition practice. Forty-seven per cent of units transfer five or fewer patients with chronic kidney disease (CKD) stage 5 per year to a median of five adult centres, with higher numbers of CKD stages 2-4 patients. Seventy-three per cent of units were required by the hospital or government to transfer patients by a certain age. Eighty per cent of units commenced transition planning after the patient turned 15 years of age and usually within 1-2 years of the compulsory transfer age. Forty-seven per cent of units used a transition or transfer clinic. Prominent barriers to effective transition were patient and parent attachment to the paediatric unit and difficulty in allowing the young person to perform self-care., Conclusions: Whereas awareness of the consensus statement is suboptimal, it has had some impact on practice. Adult nephrologists receive transferred patients infrequently, and the process of transition is introduced too late by paediatricians. Government- and hospital-driven age-based transfer policies distract focus from the achievement of competencies in self care. Variable use of transition clinics, written patient information and support groups is probably due to economic and human-resource limitations. The consensus statement provides a standard for evolving and evaluating transition policies jointly agreed upon by paediatric and adult units.

Protein-energy wasting (PEW) is defined as a state of decreased body protein mass and fuel reserves (body protein and fat mass) and is a common complication of chronic kidney disease (CKD). It is multifactorial: the main causative factors are hormonal imbalances and a low nutrient intake, but low residual renal function, inadequate dialysis dose, chronic inflammation and metabolic acidosis are other important contributory factors. Adult PEW has been defined, but there is no accepted definition of pediatric PEW and consequently no precise diagnostic criteria. Assessing nutritional status in children is also complicated by the absence of a gold standard, specific abnormalities in body composition, and the slowly progressive course of the disease. The evaluation of PEW should take into account all of its pathogenetic aspects, which include dietary assessment, clinical and anthropometric assessment (based on weight, height, and body mass index), a panel of biochemical parameters, and a normalized protein catabolic rate (in the case of adolescents on hemodialysis). Bioimpedance indices can be used in individual patients on a regular basis in centers with expertise. The longitudinal follow-up data relating to the above parameters are valuable for comparing patient and normative data. Given the complex nature of PEW, only a multidisciplinary approach can provide an accurate assessment of nutritional status and its derangements in children with CKD and on dialysis.

Background: Intradialytic exercise has been poorly investigated in pediatric patients on chronic hemodialysis (HD). The aim of this study was to assess the acceptability, safety and efficacy of intradialytic exercise in children and young adults on HD., Methods: The intradialytic exercise program consisted of 30-min sessions of intra-HD exercise using a cycloergometer two to three times a week for 3 months. Study endpoints were the 6-min walking test (6MWT) distances, lung function, number of stands in the chair test, lower extremity strength (LES), anthropometry, dietary intake, dialysis adequacy, incidence of symptomatic sessions, biochemistry and left ventricular mass index., Results: Ten pediatric patients with a median age of 15.3 (range 9.1-24.2) years were enrolled. Two of these underwent kidney transplantation; the remaining eight completed the study and adapted well to the exercise program. At the end of the 3-month study period, all patients had significantly improved results for the 6MWT (+4.9 %; p < 0.05), chair test (+19 %; p < 0.05) and LES (+29.3 %; p < 0.05). Pre-HD albumin, creatinine and total protein levels and post-HD creatinine levels had also significantly improved. The incidence of symptomatic sessions did not increase during the study period. No adverse events occurred., Conclusions: Based on our results, we conclude that a 30-min exercise program of intradialytic cycling is feasible for the majority of pediatric patients on chronic HD and will be well accepted. Such an exercise program can lead to a significant improvement in the exercise capacity of this patient population.

Background: Many factors may impact upon choice of renal replacement therapy (RRT) for children and adolescents, including patient and family choice, patient size and distance from the renal centre as well as logistic issues such as facilities and staffing at the unit. We report a survey of factors influencing treatment choice in 14 European paediatric nephrology units., Methods: A questionnaire was developed by consensus and completed by 14 members of the European Paediatric Dialysis Working Group on facilities, staffing and family assessments impacting on choice of therapy as well as choice of therapy for 97 patients commencing initial RRT in 2011., Results: All units offered all modalities of RRT, but there were limitations for pre-emptive transplantation (PET) and largely adult surgical dependence for creation of arteriovenous fistulae and transplantation. The average waiting time for a deceased donor kidney was 18.5 (range 3-36) months. Full time dietetic support was available in six of the 14 units. There was no social worker, psychology, play therapy or teaching support in three, two, seven and four units, respectively. Assessment by other members of the multidisciplinary team and home visits before choice of therapy was carried out in 50 % of units, and although all patients were discussed at team meetings, the medical opinion predominated. In terms of types of RRT, 50 % of patients were commenced on chronic peritoneal dialysis (PD), 34 % on haemodialysis (HD) and 16 % underwent pre-emptive transplantation (PET). Chronic PD predominated in patients aged <5 years and HD predominated in those aged >10 years. Patient and family choice and age or size of patient were predominant factors in choice of therapy with a predictable decline in renal function favouring PET and social factors HD., Conclusions: Chronic peritoneal dialysis predominated as primary choice of RRT, especially in younger children. The PET rates remain low. The influence of surgeons predominanted, and national transplant rules may be significant. Most units had insufficient multiprofessional support, which may impact upon initial choice of therapy as well as sustaining families through RRT.

Background: Alport syndrome (AS) is a progressive hereditary glomerular disease. Recent data indicate that aldosterone promotes fibrosis mediated by the transforming growth factor-β1 (TGF-β1) pathway, which may worsen proteinuria. Spironolactone (SP) antagonizes aldosterone and this study aimed to evaluate the efficacy of SP in reducing proteinuria and urinary TGF-β1 excretion in proteinuric AS patients., Methods: The study involved ten children with AS, normal renal function, and persistent proteinuria (>6 months; uPr/uCr ratio >1). SP 25 mg once a day for 6 months was added to existing ACE inhibitor treatment with or without angiotensin-II receptor blockade. Urine and blood samples were examined monthly. Urinary TGF-β1 levels were measured twice before and three times during SP treatment. Plasma renin activity (PRA) and serum aldosterone levels were also measured. In eight patients, uProt/uCreat was also assessed after 9 months and 12 months of SP treatment., Results: After beginning SP therapy, all patients showed significant decrease in mean uProt/uCreat ratio (1.77 ± 0.8 to 0.86 ± 0.6; p < 0.001) and mean urinary TGF-β1 levels (104 ± 54 to 41 ± 20 pg/mgCreatinine; p < 0.01), beginning after 30 days of treatment and remaining stable throughout SP administration. PRA remain unchanged, and mean serum aldosterone increased from 105 ± 72 pg/ml to 303 ± 156 pg/ml (p < 0.001). The only side effect was gynecomastia in an obese boy. After 1 year of therapy, mean uProt/uCreat remains low (0.82 ± 0.48)., Conclusions: Addition of SP to ACE-I treatment with or without angiotensin II receptor blokers (ARB) significantly reduced proteinuria. This was mediated by decreased urinary TGF-β1 levels and not associated with major side effects.

Background: To provide recommendations for the care of infants with stage 5 chronic kidney disease (CKD5)., Setting: European Paediatric Dialysis Working Group., Data Sources: Literature on clinical studies involving infants with CKD5 (end stage renal failure) and consensus discussions within the group., Recommendations: There has been an important change in attitudes towards offering RRT (renal replacement therapy) to both newborns and infants as data have accumulated on their improved survival and long-term outcomes. The management of this challenging group of patients differs in a number of ways from that of older children. The authors have summarised the basic recommendations for treating infants with CKD5 in order to support the multidisciplinary teams who endeavour on this difficult task.

Background: The simultaneous use of plasma-exchange (PE) and haemodialysis (HD), known as tandem PE and HD (TPH), may be an additional resource for treating patients who need both therapies at the same time. However, little experience is reported in the paediatric setting., Case-Diagnosis/treatment: We retrospectively reviewed the TPH sessions performed in the last 5 years in our unit. Thirty-nine TPH treatments in eight pediatric patients were traced. The median age of the patients was 10.5 (range 5.1-19.2) years, and median weight was 27.6 (range 14.7-66.2) kg. Indications for TPH were atypical haemolytic uremic syndrome due to factor H or factor I dysregulation, or to a not yet defined abnormality, in most of the sessions (34/39 sessions). The remaining five sessions were performed for vasculitis, focal segmental glomerulosclerosis and hyperimmunization in a patient waiting for kidney transplant. In all treatments, TPH was completed and reached the desired ultrafiltration and substitution volumes; the duration of PE was shorter than that of HD. No significant adverse events were observed., Conclusions: In those rare patients who require both PE and HD, TPH can improve their quality of life by reducing the time spent in extracorporeal circulation. This tandem treatment is safe and well-tolerated, even in subjects of relatively small body size.

Introduction: Major indications for peritoneal dialysis catheter removal include chronic exit-site infection (ESI) or tunnel infection (TI). No consensus on the optimal treatment of these infections in children exists., Patients: During the last 10 years, 13 patients (7 females, mean age 56 months) on peritoneal dialysis were treated for recurrent ESI (N: 4) or TI (N: 9). Staphylococcus aureus (12 patients) and Pseudomonas aeruginosa (1 patient) were isolated. All patients had a double-cuff straight Tenchkoff catheter and underwent the shaving of the external cuff, with a new tunnel tightly adherent to the catheter, and an exit-site in the opposite abdominal region. A mean follow-up of 31 months/catheter demonstrated no recurrence of ESI and TI., Discussion: Little pediatric experience with cuff shaving exists: reported catheter salvage rates are 48-100%. In our experience, good results were obtained by shaving off the external cuff and re-creating a new tunnel, with a different course, strictly adherent to the catheter. This measure seems to guarantee an effective barrier against infections, while obviating the need of the external cuff., Conclusions: Sometimes, in case of recurrent ESI or TI, the external cuff may facilitate the persistence of bacteria. A conservative surgical treatment offers good results in children.

Protein-calorie malnutrition, otherwise known as cachexia, is a common problem in children undergoing chronic peritoneal dialysis (PD) and is a frequent source of significant morbidity and mortality. Recent evidence suggests that the main factors involved in the pathogenesis are metabolic acidosis, a decreased response to anabolic hormones, and chronic inflammation, associated with hormonal imbalances and an increased metabolic rate. Given the complexity and multifactorial nature of cachexia, the assessment of nutritional status in children on PD requires a complete history and physical examination; assessment of dietary intake, biochemical indices, and anthropometry; and possibly bioimpedance analysis and combined score systems. Its management should likewise be multidisciplinary and include ensuring an adequate energy and protein intake; optimal metabolic control, with the correction of acidosis, anaemia, and hyperparathyroidism; an optimal (or at least adequate) dialysis dose; and, if necessary, prescription of specific drugs such as recombinant human growth hormone.

In most Asian subjects with postural proteinuria, ultrasonic imaging and Doppler flow scanning disclose entrapment of the left renal vein in the fork between the aorta and the superior mesenteric artery. Little information is available on the possible occurrence of left venal rein entrapment in European subjects with postural proteinuria. Renal ultrasound with Doppler flow imaging was therefore performed on 24 Italian or Swiss patients with postural proteinuria (14 girls and ten boys, aged between 5.2 years and 16 years). Signs of aorto-mesenteric left renal vein entrapment were noted in 18 of the 24 subjects. In conclusion, aorto-mesenteric left renal vein entrapment is common also among European subjects with postural proteinuria.

The evaluation of urinary erythrocyte morphology (UEM) has been proposed for patients with isolated microscopic haematuria (IMH) to early orientate the diagnosis towards a glomerular or a nonglomerular disease. However, to date, the role of this test in patients with IMH has very rarely been investigated. Sixteen patients (ten children, six adults) with persistent IMH classified as glomerular on the basis of repeated UEM evaluations (55 urine samples, two to eight per patient) were submitted to renal biopsy. This showed a glomerular disease in 14/16 patients (87.5%) (nine thin basement membrane disease; three Alport syndrome; two other), whereas in two patients, no abnormalities were found. Of four microscopic criteria investigated to define a IMH as glomerular, >80% dysmorphic erythrocytes were not found in any sample, >or=40% dysmorphic erythrocytes alone were seen in seven samples (12.7%), >or=5% acanthocytes alone in 15 samples (27.3%) and erythrocytic casts in six samples (10.9%). There was >or=40% dysmorphic erythrocytes associated with >or=5% acanthocytes in 25 samples (45.5%). Sensitivity and positive predictive values in diagnosing a glomerular haematuria were 59.2% and 90.6%, respectively, for >or=40% dysmorphic erythrocytes, 69.4% and 85% for >or=5% acanthocytes/G1 cells and 12.2% and 100% for erythrocytic casts. Our findings demonstrate that the evaluation of UEM is useful to identify patients with an IMH of glomerular origin.

Despite advancements in catheter design and dialysis technique, catheter related complications still remain a common clinical problem in paediatric patients on chronic peritoneal dialysis (PD); in particular, infections are a common cause of patient's morbidity and technique failure. In the present paper, data on 89 catheters implanted between January 1986 and December 2002 are reviewed to analyse the major causes of complications and/or PD failure and to ascertain their optimal management. A total of 89 catheters were implanted in 78 patients at the start of chronic PD: 26 in children under 2 years of age, 14 in children aged 2-5 years and 49 in patients over 5 years. Mean age of patients was 76.1 +/- 73.0 months and median treatment time 14.5 +/- 13.1 months. All catheters were surgically implanted and partial omentectomy was performed in 70% of cases. Straight Tenckhoff catheters were used in 70 cases (78%), curled ones in 19 (22%). Sixty-three catheters (71%) had two cuffs, 26 (29%) a single cuff. The entry-site was the midline in 34 patients (38%) and the paramedian line in 55 patients (62%). Catheter survival rate was 80% at 12 months, 62% at 24 months and 58% at 36 and 48 months, respectively. The incidence of catheter-related complications was one episode every 6.4 PD-months, and they were mainly represented by peritonitis (61%), exit-site infections and tunnel infection (ESI + TI: 23%), catheter obstruction (5%), dislocation (3.5%), leakage (2.5%). After the introduction of curled single-cuff catheters, a considerable reduction in the peritonitis incidence was observed during the last 7 years. A more prolonged catheter survival was observed in older children (>5 vs. <2 years: P < 0.05). Leakage was less common in catheters with paramedian entry-site compared with catheters implanted on the midline. In 7 out of 11 (64%) patients with catheter obstruction, omentectomy had not been performed. Single-cuff catheters had a lower infection-rate than double-cuff catheter (P < 0.01). Single cuff-curled Tenckhoff catheter can be considered the first choice catheter. Single cuff-catheters are not associated with an increase of infections. The surgical technique requires a strict adherence to a standardized procedure and a dedicated team, in order to obtain a reduction of the complications, a prolonged catheter duration and a better quality of life.

Brain abscesses caused by Nocardia are rare, but it is very important to detect and treat them early because the associated mortality is 3 times higher than that associated with other bacterial brain abscesses. This infection is prevalent among adults on long-term immunosuppressive therapy; we report the case of a male kidney transplant recipient aged 12.7 years who developed early multiple Nocardia-induced brain abscesses that were successfully treated with linezolid, a novel antibiotic therapy.

Infectious complications of the central venous catheter (CVC) are a major source of morbidity among children treated with hemodialysis (HD), with catheter-related bloodstream infections (CRBSI) being the most important clinical manifestations. As only a few studies of children on HD have been published, the management of CVC-related infections in this population is mainly based on data derived from adults or occasionally from children not affected by end-stage renal disease (ESRD). The aim of this review is to discuss current knowledge concerning the epidemiology, prevention, and treatment of catheter-related infections in children on HD. Catheters impregnated with antibiotics/antiseptics, lock antibiotic prophylaxis, nasal mupirocin, and the application of ointments at the exit-site have all been proposed as means of reducing the risk of CVC infections, but their real efficacy in the pediatric population has not yet been demonstrated. Furthermore, it is not clear how long antibiotic therapy should be continued, and there is still debate as to whether the catheter has to be removed. We propose some practical guidelines for the management of CRBSI in children with percutaneously inserted and surgically implanted HD catheters, but a number of unresolved clinical issues still remain, which will require prospective clinical trials specifically performed in pediatric patients with ESRD.

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).

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.

Peritoneal teledialysis (telePD) is a modem-based communication link between the patients' cyclers and a computer in the dialysis unit that allows the transmission and storage of a series of automated peritoneal dialysis (APD) treatment data. In order to evaluate the usefulness of telePD in quantifying the problems that may occur during pediatric APD, we retrospectively studied four patients with a median age of 14.1+/-1.8 years during their initial months of telePD. The selection criteria were potential non-compliance in two cases (patients 1 and 2) and catheter malposition or fibrin occlusion in two (patients 3 and 4). The patients were treated using a Fresenius PD Night Cycler with teledialysis software. Thirty consecutive treatments per patient in the 1st and 4th months were examined, and a series of treatment parameters was calculated. The percentage of treatments with alarms and the number of alarms per treatment were high in both the 1st and the 4th month, particularly in patients 3 and 4. The main causes of the alarms were tube kinking, catheter malfunction, fibrin occlusion, and failure of electrical power. The number of shortened treatments significantly decreased in the 4th month of telePD. One non-compliant family was identified during the 1st month of PD, but psychosocial support helped to decrease the number of shortened treatments due to non-compliance in the 4th month. During the 4th month of telePD, the dwell time/total treatment time ratio (which represents the time of contact between the peritoneum and dialysis fluid) increased as a result of technical interventions aimed at reducing the infusion plus drain time. In conclusion, telePD proved to be useful in detecting and solving the clinical and technical problems of APD.

Verocytotoxin-producing Escherichia coli(VTEC) infections cause most cases of hemolytic uremic syndrome (HUS); 10-30% of patients, however, are negative for VTEC infection. The etiology of HUS in VTEC-negative cases remains poorly understood. Before the association between VTEC infection and HUS was recognized, sporadic cases of HUS with enterovirus infection were reported in the literature. Since May 1988, most cases of HUS in Italy have been reported to the Italian surveillance system, and in 73% of these, evidence of VTEC infection was demonstrated. The aim of this study was to determine whether the frequency of enteroviral infections was different in the acute phase of VTEC-positive and VTEC-negative HUS. Eighty-nine patients were investigated for enteroviral infection, of whom 58 were VTEC positive and 31 VTEC negative. Two serum samples from each patient were examined for seroconversion to enterovirus (coxsackie, echovirus, and picornavirus) by a complement fixation test. Serological evidence of acute infection with non-polio enterovirus was found in 33 patients (37%) [20/58 (34.5%) VTEC positive and 13/31 (41.9%) VTEC negative]. There was no statistically significant difference between the two groups. These results demonstrate that there are no significant differences for enteroviral infection in VTEC-positive and VTEC-negative patients and, therefore, enteroviral infections should not be considered a cause of HUS in VTEC-negative children.

In pediatric kidney transplant recipients, tacrolimus has been proposed either for primary immunosuppression or as a rescue agent for refractory acute rejection, chronic rejection, and cyclosporine toxicity. This paper describes our experience with tacrolimus conversion from cyclosporine-based therapy in six selected cases: four due to refractory acute rejections unresponsive to conventional therapy, one to chronic graft rejection, and one to cyclosporine-related hypertrichosis. A "simple-switch" conversion was used without any overlap, starting with a dose of 0.2 mg/kg per day. The time to conversion varied from 10 to 730 days after the transplant. In the patients with acute rejection, the median time to reversal after tacrolimus conversion was 12 days. The symptoms of the patient with cyclosporine toxicity completely resolved without any loss of allograft function. The patient with chronic rejection maintained stable renal function for more than 1 year after conversion. A new onset of post-transplant diabetes mellitus and dose-related nephrotoxicity were recorded as adverse events. In conclusion, our experience suggests that tacrolimus can play an important role in the salvage treatment of pediatric kidney transplantations with deteriorating graft function due to acute rejection refractory to standard therapy. Tacrolimus conversion also provides excellent results in the presence of cyclosporine toxicity.