Diversity of Pediatric Workforce and Education in 2012 in Europe: A Need for Unifying Concepts or Accepting Enjoyable Differences?

OBJECTIVE: To evaluate differences in child health care service delivery in Europe based on comparisons across health care systems active in European nations. STUDY DESIGN: A survey involved experts in child health care of 40 national pediatric societies belonging both to European Union and non-European Union member countries. The study investigated which type of health care provider cared for children in 3 different age groups and the pediatric training and education of this workforce. RESULTS: In 24 of 36 countries 70%-100% of children (0-5 years) were cared for by primary care pediatricians. In 12 of 36 of countries, general practitioners (GPs) provided health care to more than 60% of young children. The median percentage of children receiving primary health care by pediatricians was 80% in age group 0-5 years, 50% in age group 6-11, and 25% in children >11 years of age. Postgraduate training in pediatrics ranged from 2 to 6 years. A special primary pediatric care track during general training was offered in 52% of the countries. One-quarter (9/40) of the countries reported a steady state of the numbers of pediatricians, and in one-quarter (11/40) the number of pediatricians was increasing; one-half (20/40) of the countries reported a decreasing number of pediatricians, mostly in those where public health was changing from pediatric to GP systems for primary care. CONCLUSIONS: An assessment on the variations in workforce and pediatric training systems is needed in all European nations, using the best possible evidence to determine the ideal skill mix between pediatricians and GPs.

Early kidney transplantation improves neurocognitive outcome in patients with severe congenital chronic kidney disease.

Renal replacement therapy has become available for the majority of patients suffering from severe congenital chronic kidney disease (CKD). Data on the long-term neurocognitive outcome and the impact of early kidney transplantation (KTx) in this setting is unclear. Neurocognitive outcomes in 15 patients (11 male) with isolated congenital CKD (stage 3-5) requiring KTx at a mean age of 2.8 ± 1.3 were assessed at a mean age of 8.3 ± 1.4 years. Patients underwent neurological examination and testing for neuromotor and neurocognitive function using three independent tests. Pre-emptive KTx was performed in six patients, and nine patients were dialyzed prior to KTx for a mean period of 11.1 ± 8.6 months. Neuromotor function was abnormal in 8/15 patients. HAWIK-III showed a global intelligence quotient (IQ) of 93.5 ± 11.4 (P = 0.05) due to a significantly reduced performance IQ of 89.1 ± 11.3 (P < 0.01). In three patients, the global IQ was clinically significantly reduced by >1 SD to <85. In patients with neuromotor dysfunction, performance IQ was lower than in patients with normal neuromotor function (83.8 ± 10.2 vs. 96.2 ± 9.0, P = 0.04). Time on dialysis was inversely correlated to verbal IQ (r = 0.78, P = 0.02). Pre-emptive KTx and duration of dialysis treatment <3 months was associated with superior neurocognitive outcome. Early (pre-emptive) KTx results in superior long-term neurocognitive outcome in children with severe congenital CKD.

Growth and maturation improvement in children on renal replacement therapy over the past 20 years.

BACKGROUND: The attainment of normal growth and maturation remains a major challenge in the management of children and adolescents requiring renal replacement therapy (RRT). METHODS: We compared growth and maturation in 384 German children with RRT who were followed between 1998 and 2009 with 732 children who were enrolled in the European Dialysis and Transplant Association (EDTA) Registry from 1985 to 1988; of these children, 78 and 88 %, respectively, were transplanted. RESULTS: The data on the German patients included in the EDTA registry did not differ significantly from those of the patients from other European countries. Overall, the mean height standard deviation score (SDS) has improved over the past 20 years from -3.03 to -1.80 (p < 0.001). Until the age of 6 years, the difference in height SDS was not significant, whereas it improved significantly in adolescence (-3.40 vs. -1.52; p < 0.001). Significant improvements in the delay of the pubertal growth spurt, age at menarche, bone maturation and body mass index (BMI) were noted in the recent German group compared to the EDTA group (each p < 0.001). CONCLUSIONS: Our findings demonstrate a marked improvement of growth and maturation in paediatric patients on RRT during the past 20 years.

Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy.

Alport syndrome inevitably leads to end-stage renal disease and there are no therapies known to improve outcome. Here we determined whether angiotensin-converting enzyme inhibitors can delay time to dialysis and improve life expectancy in three generations of Alport families. Patients were categorized by renal function at the initiation of therapy and included 33 with hematuria or microalbuminuria, 115 with proteinuria, 26 with impaired renal function, and 109 untreated relatives. Patients were followed for a period whose mean duration exceeded two decades. Untreated relatives started dialysis at a median age of 22 years. Treatment of those with impaired renal function significantly delayed dialysis to a median age of 25, while treatment of those with proteinuria delayed dialysis to a median age of 40. Significantly, no patient with hematuria or microalbuminuria advanced to renal failure so far. Sibling pairs confirmed these results, showing that earlier therapy in younger patients significantly delayed dialysis by 13 years compared to later or no therapy in older siblings. Therapy significantly improved life expectancy beyond the median age of 55 years of the no-treatment cohort. Thus, Alport syndrome is treatable with angiotensin-converting enzyme inhibition to delay renal failure and therapy improves life expectancy in a time-dependent manner. This supports the need for early diagnosis and early nephroprotective therapy in oligosymptomatic patients.

Sequential maintenance therapy with cyclosporin A and mycophenolate mofetil for sustained remission of childhood steroid-resistant nephrotic syndrome.

BACKGROUND: There is currently no established standard for maintenance therapy of steroid-resistant nephrotic syndrome (SRNS). We report the long-term clinical course, medication, pharmacokinetic data, and renal function of 23 children with primary, non-familial SRNS with focal segmental glomerulosclerosis (FSGS). METHODS: To achieve initial remission, patients were treated with high-dose intravenous (i. v.) methylprednisolone and oral cyclosporin A (CsA). Maintenance therapy included transient alternate day oral prednisolone, CsA and angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers. In 18 patients, mycophenolate mofetil (MMF) (adjusted to achieve blood mycophenolic acid trough concentrations > 2 µg/mL) was sequentially added, and 16 patients were converted to MMF monotherapy. RESULTS: During a mean follow-up time of 7.0 years (1.7-16.5 years; cumulative observation time 161 patient-years), sustained remission could be achieved in all patients. Five of 23 patients (21%) experienced 10 relapses; all responded to relapse therapy. Maintenance therapy could be permanently discontinued in seven patients (30%). After conversion from CsA to MMF, renal function improved significantly; the eGFR at last follow-up was 137 (range 106-198) mL/min × 1.73 m(2). The mean number of anti-hypertensive drugs decreased from 1.86 per patient after initial remission to 0.57 on MMF monotherapy (P < 0.002). CONCLUSIONS: The data of this uncontrolled retrospective study indicate that in children with SRNS/FSGS achieving initial remission, a sequential steroid-free therapy consisting of a combination of CsA and MMF followed by MMF alone (with the addition of ACE inhibitors and angiotensin receptor blockers), can provide sustained long-term remission, preservation of renal function and better control of blood pressure.

Diagnostic pathways for exclusion and diagnosis of kidney diseases.

In 2006, the German Society for Clinical Chemistry and Laboratory Medicine together with the Society of Nephrology founded a working group with the aim to develop diagnostic pathways for the detection and differentiation of renal diseases. Based on existing recommendations, these pathways may be structured to be a basis for implementation into hospital and laboratory information systems. The present paper describes the contents of these pathways regarding glomerular filtration rate, hematuria, leukocyturia and proteinuria.

Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease.

Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides.

Effective treatment of anemia in pediatric kidney transplant recipients with methoxy polyethylene glycol-epoetin beta.

MPG-EPO is a continuous erythropoietin receptor activator with a longer half-life than darbepoetin, hence requires less frequent injections. It has been successfully used in adults, but currently, there are no published data available for its use in children. This pilot study was performed to verify the effect of MPG-EPO on Hb levels in children. Twelve patients (age 6.4-17.2 yr) were treated with MPG-EPO as an individual "Heilversuch" according to German law after RTx. Five patients were switched from DA, and seven were naïve to erythropoietin. Over a period of six months, Hb levels were measured monthly. A median MPG-EPO dose of 2.5 µg/kg was administered intravenously in a single dose every four wk. The median Hb value increased in naïve patients from 9.9 to 11.2 g/dL (median, p = 0.004) and from 10.3 to 11.6 g/dL (median, p = 0.39) in patients switched from DA to MPG-EPO. No adverse events secondary to MPG-EPO therapy were detected. Our results indicate that a once-monthly injection of MPG-EPO is an effective treatment of anemia in children after renal transplantation. Larger randomized trials will have to confirm our findings.

Regional citrate anticoagulation--a safe and effective procedure in pediatric apheresis therapy.

Regional citrate anticoagulation (RCA) has been considered to be a standard component of pediatric apheresis therapy for more than a decade. However, data on dosing recommendations and evaluations of the effectiveness and safety of anticoagulation are rarely found in published reports. The aim of this retrospective analysis was to present our single-center experience with RCA in pediatric apheresis therapy with the aim of developing an operating procedure. Five children aged 7-14 years underwent a total of 72 (range 3-44) therapeutic apheresis sessions with RCA in the form of immunoadsorption therapy (2 patients), low-density lipoprotein (LDL)-apheresis (1 patient), and plasmapheresis (two patients). A 3% citrate solution was used. Citrate flow was started at 4.0% of the blood flow velocity and was adapted to match post-filter ionized calcium levels ≤ 0.30 mmol/l. Once the patient's ionized calcium fell to <1.05 mmol/l, an intravenous 10% calcium gluconate solution was administered. Twenty pediatric apheresis patients who received standard heparinization, matched for age, body surface area, processed plasma volume, and blood flow velocity, were enrolled in the study as a comparison group. No side effects were experienced in 72 apheresis session. The 3% citrate solution had to be reduced gradually during the apheresis session and was infused at a mean of 2.8-3.8% of the blood flow rate. Serum bicarbonate levels before and after the apheresis session with RCA [23.9 (range 18.9-30.1) vs. 26.3 (20.2-33.0) mmol/l, respectively] were significantly different (p=0.013). All patients required intravenous calcium substitution to maintain serum calcium levels within the physiological range. Due to the administration of the 3% citrate solution and calcium, all patients significantly gained weight during the procedure, with a median weight gain of 2.5% (p<0.001). The extra fluid load caused problems in patients with kidney failure. Our regimen with RCA is safe, feasible, and effective in pediatric therapeutic apheresis therapy. For RCA in apheresis, we recommend (1) a citrate (3%) flow of 3.3% of the blood flow, (2) prophylactic intravenous calcium substitution from the beginning, and (3) a more highly concentrated citrate solution in the case of oliguric patients.

Haemorrhagic complications in paediatric dialysis-dependent acute kidney injury: Incidence and impact on outcome.

BACKGROUND: The occurrence of haemorrhagic complications in children with dialysis-dependent acute kidney injury (dAKI) and its contribution to morbidity and mortality is unclear. The objective of this retrospective analysis was to investigate the dialysis modalities, haemorrhagic complications and outcome of dAKI in children and adolescents. METHODS: Data from 198 children and adolescents (median age 3 years, range 0-18 years) with dAKI from 2000 to 2006 was analysed for bleeding risks, haemorrhagic complications, underlying diseases, associated variables and mortality. One hundred and seven patients underwent peritoneal dialysis (PD), 71 continuous haemofiltration (CVVH) and 20 intermittent haemodialysis (HD) using systemic heparinization. RESULTS: Fifty-three of 198 children (27%) suffered from one or more haemorrhagic complications; 63% of these complications were life-threatening. Bleeding was mainly diffuse (35 of 53). The incidence of haemorrhagic complications was significantly higher in patients on HD or CVVH compared to those on PD. Regression analysis of data showed that previous bleeding episodes or surgery, the underlying disease and the presence of multi-organ dysfunction syndrome (MODS) were strongly associated with haemorrhagic complications (P = 0.001). The overall mortality rate was 37%. Death was directly caused by bleeding complications (severe lung haemorrhage) in only three cases. Highly significant associated factors for mortality were the underlying disease, very young age, presence of MODS and acute haemorrhagic complications (P < 0.001). CONCLUSIONS: We conclude that bleeding is a frequent and life-threatening complication in children with dAKI. Haemorrhagic complications seem to be a predictive, rather than a causative, factor for mortality.

Self-adjustment of phosphate binder dose to meal phosphorus content improves management of hyperphosphataemia in children with chronic kidney disease.

BACKGROUND: Hyperphosphataemia in patients with chronic kidney disease (CKD) is associated with mineral and bone disorder and increased cardiovascular mortality. Despite phosphate binders (PB), nutrition counselling and dialysis therapy, the prevalence of hyperphosphataemia remains unacceptably high. It was hypothesized that an inadequate relation of PB dose to meal inorganic phosphorus (iP) content may be an important factor for failure of phosphate management. METHODS: The innovative 'Phosphate Education Program' (PEP) bases on patient empowerment to eye-estimate meal iP content by newly defined 'Phosphate Units' (PU; 1 PU per 100 mg phosphorus) and self-adjust PB dosage to dietary iP intake by an individually prescribed PB/PU ratio (PB pills per PU). In a prospective study, 16 children (aged 4-17 years) with CKD and their parents were trained with the PEP concept and followed up for 24 weeks for changes in serum electrolyte levels, dietary behaviour and PB dose. RESULTS: Within 6 weeks after PEP training, the percentage of children with serum phosphate (PO) >1.78 mmol/l dropped from 63% (10/16) to 31% (5/16). Mean serum PO level decreased from 1.94 ± 0.23 at baseline to 1.68 ± 0.30 (SD) mmol/l in Week 7-12 (P = 0.02) and to 1.78 ± 0.36 (SD) mmol/l in Week 19-24 (P = 0.2), whereas serum calcium [2.66 ± 0.3 vs 2.60 ± 0.23 (SD) mmol/l in Weeks 7-12 (P = 0.45) and 2.66 ± 0.23 (SD) mmol/l in Week 19-24 (P = 0.21)] and serum potassium [4.69 ± 0.48 vs 4.58 ± 0.68 (SD) mmol/l in Week 7-12 (P = 0.40) and 4.65 ± 0.49 (SD) mmol/l in Week 19-24 (P = 0.73)] remained unchanged. The mean daily PB dose rose from 6.3 ± 2.9 to 8.2 ± 5.4 (SD) pills during observation period with an increased meal-to-meal variability (P = 0.04). Dietary iP intake was not affected by PEP concept. CONCLUSION: The empowerment of children with CKD and their parents to self-adjust PB dose to eye-estimated meal iP content significantly improved management of hyperphosphataemia without reducing dietary iP intake.

Prematurity, small for gestational age and perinatal parameters in children with congenital, hereditary and acquired chronic kidney disease.

BACKGROUND: Low birth weight has been identified as a risk factor for chronic kidney disease (CKD). METHODS: We analysed perinatal parameters taken from the National Birth Certificates of 435 children with CKD stages 3-5 of different aetiology and time of onset of CKD. Diseases were classified as congenital with onset of renal disease during fetal life (n = 260; 60%), hereditary as genetically determined with onset after 3 months of life (n = 93; 21%) and acquired CKD (n = 82; 19%). RESULTS: The rates of prematurity and small for gestational age (SGA) were elevated in children with congenital (39.3% and 29.2%), hereditary (24.7% and 22.6%) and acquired CKD (15.5% and 29.3%); these compared to 8% (for both) in the normal population. Newborns with congenital CKD had a significantly lower gestational age [median 38 weeks, interquartile range (IQR) 36-40 weeks] than those with hereditary (39.9 weeks, IQR 37.5-40 weeks) or acquired CKD (40 weeks, IQR 38-40 weeks; P < 0.001). Median birth weight and length were lower in newborns with congenital than in hereditary and acquired diseases [2975 g (IQR 2460-3420 g) versus 3250 g (IQR 2740-3580 g) and 3260 g (IQR 2858-3685 g) (P < 0.01); 49 cm (IQR 47-52) versus 50 cm (IQR 48-52.8) and 51 cm (IQR 49-53) (P < 0.01)]. Head circumference was smaller (P < 0.05), and Apgar scores were lower (P < 0.005) in newborns with congenital diseases than in hereditary and acquired diseases. CONCLUSIONS: Children with congenital CKD had the highest rate of prematurity, a significantly lower birth weight, length, head circumference and Apgar score than newborns with hereditary or acquired CKD. Irrespective of the aetiology of CKD, all of the children had a significantly higher rate of SGA and prematurity than the reference population. We conclude that both SGA and prematurity predispose for advanced renal disease in childhood and that fetal kidney disease impairs fetal growth.

Regional citrate anticoagulation is safe in intermittent high-flux haemodialysis treatment of children and adolescents with an increased risk of bleeding.

BACKGROUND: Regional citrate anticoagulation (RCA) is strongly recommended for adults with an increased risk of bleeding complications. The objective of this retrospective analysis was to evaluate an RCA protocol concerning feasibility and safety in intermittent high-flux haemodialysis (iHD) treatment in children and adolescents. METHODS: Eighteen children and adolescents aged 5-17 years (median 15 years) underwent 74 iHD treatment sessions with RCA. Twelve of 18 patients presented with overt local or diffuse haemorrhage before beginning the HD sessions, and six had an increased risk of haemorrhagic complications. Forty children on acute haemodialysis with general heparin anticoagulation, matched for bleeding risk, age and body surface area, served as a control group. Citrate 3% solution was begun with 3.3% blood flow rate, and calcium gluconate 10% substitution was started with 0.4% of blood flow rate. Citrate flow was adapted to achieve a post-filter ionized calcium of ≤0.30 mmol/L; calcium substitution was adapted to maintain the patients' serum calcium levels within the physiological range. Calcium-free dialysis fluid was used. The blood flow rate ranged from 3 to 5 mL per minute and kilogram body weight. RESULTS: Regional anticoagulation was successfully achieved within the extracorporeal blood circuit, while the coagulation of all 18 patients remained within physiological parameters. No adverse effects of RCA were observed. In all 18 children, neither new haemorrhage nor worsening of the bleeding situation occurred, and in 10/12 patients, bleeding stopped during dialysis with RCA. In contrast, one-third of the control group developed new haemorrhagic complications or presented with worsening of pre-existing bleeding during haemodialysis (P = 0.006). CONCLUSION: RCA is feasible, safe and effective in paediatric intermittent haemodialysis treatment.

End-stage renal disease due to ARPKD in the first months of life: transplantation or dialysis?--two case reports.

ARPKD with renal insufficiency during the first months of life is a clinical challenge. We report on two children with ARPKD with massively enlarged kidneys requiring renal replacement therapy in early infancy. Patient 1 developed pulmonary insufficiency due to massively enlarged kidneys. At the age of six months the girl was listed for KT as "high urgency" on the Eurotransplant waiting list. A kidney from a deceased donor was pre-emptively transplanted and simultaneous nephrectomy performed. No postoperative complications were observed, and the patient was discharged from in-patient care 42 days after transplantation. Unexpectedly, she died at the age of one yr due to cerebral vascular spasms of unknown origin. Patient 2 was transferred at the age of three months to our clinic with life-threatening pulmonary insufficiency. Pre-emptive KT was not possible; therefore, bilateral nephrectomy was performed and PD begun. The boy is still doing well on PD one yr later. Pre-emptive KT and bilateral nephrectomy followed by PD are two options for infants with ARPKD and excessive kidney enlargement. PD could be complicated and in some cases become impossible by peritoneal damage during nephrectomy. On the other hand, KT covers a high risk of infections caused by immunosuppression. The decision, which method to choose, should be driven by the individual situation of the patient and the expertise of the center.

Chronic Mycoplasma pneumoniae infection in a child after renal transplantation.

Mycoplasma pneumoniae has rarely been reported in renal transplant recipients. We present the case of a 10-yr-old boy with a six-month history of chronic cough, recurrent pyrexia, and weight loss three yr after RTx. The patient's post-transplant course was complicated by recurrence of NS that resolved with plasmapheresis and PTLD, which was successfully treated with an anti-CD20 monoclonal antibody. Chest X-ray showed a round mass-like lesion in the left upper lobe; MRT, PET, and bronchoscopy ruled out a PTLD. BAL fluid revealed M. pneumoniae-DNA. A three-wk course of macrolide therapy induced rapid recovery. We conclude that M. pneumoniae infection should be considered in immunosuppressed patients with long-lasting respiratory complaints and fever of unknown origin. Antibiotic treatment should be given for a minimum of three wk.

Estimation of glomerular filtration rate in liver-transplanted children: comparison of simplified procedures using 51Cr-EDTA and endogenous markers with Sapirstein's method as a reference standard.

This study evaluated simple procedures for GFR determination in 48 liver-transplanted children. After injection of (51)Cr-EDTA, blood samples were obtained up to four h, and activity retention in the body was measured for 60 min with scintillation probes. As a reference, GFR was calculated according to Sapirstein. Simplified calculations were performed according to Brochner-Mortensen, Russel, Devaux and Oberhausen. Additionally, GFR was determined using plasma creatinine and cystatin C according to Schwartz and Filler, respectively. The reference revealed mildly reduced GFR (62 +/- 20 mL/min/1.73 m(2)). Russel's method provided the highest degree of correlation (r(2) = 0.95), the smallest bias in GFR determination (-2%), and only one false exclusion plus one false diagnosis of chronic kidney disease. Oberhausen's method with blood sampling at one h post-injection performed slightly worse (r(2) = 0.67, bias: 3%). All other methods resulted in significantly different GFR estimates compared to the reference. Nevertheless, notably, the second narrowest 95% limits of agreement (-31% to 45%) was observed using cystatin C. In conclusion, this data implies to prefer Russel's method as a simplified procedure, and if patients cannot be available long enough (four h) for measurements, Oberhausen's method instead. If radiotracer methods are not available at all or for screening GFR, cystatin C appears to be the procedure of choice.

Management of regional citrate anticoagulation in pediatric high-flux dialysis: activated coagulation time versus post-filter ionized calcium.

Recent years has seen an increasing use of regional citrate anticoagulation in pediatric dialysis. Several approaches have been described for monitoring anticoagulation in the extracorporeal circuit, such as serum citrate levels, post-filter ionized calcium (iCa), and activated coagulation time (ACT). However, no standard recommendations have yet been established for applying any of these parameters, especially for iCa. The objective of this retrospective analysis was to establish adequate coagulation management using post-filter iCa values. Normal values for ACTester-based ACT were established using a group of 64 children who were divided into two subgroups, with one subgroup comprising children without chronic kidney disease or coagulation disorder (age 1.2-17.5 years, median 9.7 years) and one consisting of 32 uremic patients (age 0.6-17.5 years, median 13.7 years). In a second group of 13 patients (aged 7-17 years), all of whom were undergoing high-flux dialysis (HD) with regional citrate anticoagulation (RCA), we assessed 73 post-filter blood samples for ionized calcium and ACT. A receiver operating characteristic graph was used to identify the iCa threshold needed to achieve adequate anticoagulation. Normal values for ACT were 90 s [2 standard deviations (SD) 72-109] in healthy children and 94 s (2 SD 75-113) in the uremic children. There was no statistically significant difference between the groups. In the children undergoing HD with RCA, the post-filter iCa level correlated with ACT (r = -0.94, p < 0.001). A post-filter iCa level of < or = 0.30 mmol/l reliably predicted an ACT >120 s. Our citrate protocol [citrate 3% rate (ml/h) approximately blood flow rate (ml/min) x 2] meets the established criteria with a high sensitivity. Based on these results, we conclude that the post-filter iCa level can be reliably used for the management of extracorporeal anticoagulation with citrate in pediatric HD. We recommend the application of our citrate prescription protocol in the setting of pediatric intermittent hemodialysis.