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Background: Protein loss and glucose absorption in children on acute peritoneal dialysis (PD) is important to inform dietary prescription, yet data are lacking in this regard. This study was a secondary analysis of a previously published crossover randomised controlled trial, aiming to describe glucose uptake and protein loss into dialysate among children with acute kidney injury (AKI) receiving PD., Methods: This secondary analysis described and compared dialysate albumin loss and glucose absorption in 15 children with AKI receiving PD or continuous flow peritoneal dialysis (CFPD). In addition, correlations between albumin loss, glucose absorption and other patient and dialysis factors were analysed., Results: Median (range) age and weight of participants were 6.0 (0.2-14) months and 5.8 (2.3-14.0) kg, respectively. Patients received approximately 8 h of dialysis on each modality; however, results were extrapolated and expressed per day. The mean ± SD albumin loss on conventional PD and CFPD was 0.3 ± 0.19 g/kg/day and 0.56 ± 0.5 g/kg/day, respectively, and the mean ± SD glucose absorption was 4.67 ± 2.87 g/kg/day and 3.85 ±4.1 g/kg/day, respectively. There was a moderate correlation between ultrafiltration and albumin loss during CFPD only (Pearson's R = 0.61; p = 0.02). There were no significant differences between PD and CFPD for either glucose absorption or albumin loss; however, the study was not powered for this outcome., Conclusions: Protein losses and glucose absorption in children on PD with AKI are significant and should be considered when prescribing nutritional content. Protein losses on CFPD were twice as high as on conventional PD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Our previously demonstrated continuous flow peritoneal dialysis (CFPD) technique in children with acute kidney injury (AKI), although effective, was manpower heavy and expensive due to the high-volume pumps required. The aim of this study was to develop and test a novel gravity-driven CFPD technique in children using readily available, inexpensive equipment and to compare this technique to conventional PD., Methods: After development and initial in vitro testing, a randomised crossover clinical trial was conducted in 15 children with AKI requiring dialysis. Patients received both conventional PD and CFPD sequentially, in random order. Primary outcomes were measures of feasibility, clearance and ultrafiltration (UF). Secondary outcomes were complications and mass transfer coefficients (MTC). Paired t-tests were used to compare PD and CFPD outcomes., Results: Median (range) age and weight of participants were 6.0 (0.2-14) months and 5.8 (2.3-14.0) kg, respectively. The CFPD system was easily and rapidly assembled. There were no serious adverse events attributed to CFPD. Mean ± SD UF was significantly higher on CFPD compared to conventional PD (4.3 ± 3.15 ml/kg/h vs. 1.04 ± 1.72 ml/kg/h; p < 0.001). Clearances for urea, creatinine and phosphate for children on CFPD were 9.9 ± 3.10 ml/min/1.73 m 2 , 7.9 ± 3.3 ml/min/1.73 m 2 and 5.5 ± 1.5 ml/min/1.73 m 2 compared to conventional PD with values of 4.3 ± 1.68 ml/min/1.73 m 2 , 3.57 ± 1.3 ml/min/1.73 m 2 and 2.53 ± 0.85 ml/min/1.73 m 2 , respectively (all p < 0.001)., Conclusion: Gravity-assisted CFPD appears to be a feasible and effective way to augment ultrafiltration and clearances in children with AKI. It can be assembled from readily available non-expensive equipment. 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.)

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.

Acute kidney injury (AKI) is an increasingly frequent complication among hospitalized children. It is associated with high morbidity and mortality, especially in neonates and children requiring dialysis. The different renal replacement therapy (RRT) options for AKI have expanded from peritoneal dialysis (PD) and intermittent hemodialysis (HD) to continuous RRT (CRRT) and hybrid modalities. Recent advances in the provision of RRT in children allow a higher standard of care for increasingly ill and young patients. In the absence of evidence indicating better survival with any dialysis method, the most appropriate dialysis choice for children with AKI is based on the patient's characteristics, on dialytic modality performance, and on the institutional resources and local practice. In this review, the available dialysis modalities for pediatric AKI will be discussed, focusing on indications, advantages, and limitations of each of them.

The number of children with acute kidney injury (AKI) requiring dialysis is increasing. To date, systematic analysis has been largely limited to critically ill children treated with continuous renal replacement therapy (CRRT). We conducted a survey among 35 European Pediatric Nephrology Centers to investigate dialysis practices in European children with AKI. Altogether, the centers perform dialysis in more than 900 pediatric patients with AKI per year. PD and CRRT are the most frequently used dialysis modalities, accounting for 39.4% and 38.2% of treatments, followed by intermittent HD (22.4%). In units treating more than 25 cases per year and in those with cardiothoracic surgery programs, PD is the most commonly chosen dialysis modality. Also, nearly one quarter of centers, in countries with a gross domestic product below $35,000/year, do not utilize CRRT at all. Dialysis nurses are exclusively in charge of CRRT management in 45% of the cases and pediatric intensive care nurses in 25%, while shared management is practiced in 30%. In conclusion, this survey indicates that the choice of treatment modalities for dialysis in children with AKI in Europe is affected by the underlying ethiology of the disease, organization/set-up of centers and socioeconomic conditions. PD is utilized as often as CRRT, and also intermittent HD is a commonly applied treatment option. A prospective European AKI registry is planned to provide further insights on the epidemiology, management and outcomes of dialysis in pediatric AKI.

Background: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce., Methods: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score., Results: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher β 2-microglobulin. The HDF cohort had lower β 2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time., Conclusions: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required., (Copyright © 2019 by the American Society of Nephrology.)

Background: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population., Methods: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m 2 ; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38)., Discussion: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD., Trial Registration: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.

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.

Ethylmalonic encephalopathy is a fatal, rapidly progressive mitochondrial disorder caused by ETHE1 mutations, whose peculiar clinical and biochemical features are due to the toxic accumulation of hydrogen sulphide and of its metabolites, including thiosulphate. In mice with ethylmalonic encephalopathy, liver-targeted adeno-associated virus-mediated ETHE1 gene transfer dramatically improved both clinical course and metabolic abnormalities. Reasoning that the same achievement could be accomplished by liver transplantation, we performed living donor-liver transplantation in an infant with ethylmalonic encephalopathy. Unlike the invariably progressive deterioration of the disease, 8 months after liver transplantation, we observed striking neurological improvement with remarkable achievements in psychomotor development, along with dramatic reversion of biochemical abnormalities. These results clearly indicate that liver transplantation is a viable therapeutic option for ETHE1 disease., (© The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Mortality among critically ill children requiring continuous renal replacement therapy (CRRT) is high. Several factors have been identified as outcome predictors. Many studies have specifically reported a positive association between the fluid overload at CRRT initiation and the mortality of critically ill pediatric patients., Methods: This study is a retrospective single-center analysis including all patients admitted to the pediatric intensive care unit (PICU) of our hospital who received CRRT between 2000 and 2012. One hundred thirty-one patients were identified and subsequently classified according to primary disease. Survival rates, severity of illness and fluid balance differed among subgroups. The primary outcome was patient survival to PICU discharge., Results: Overall survival to PICU discharge was 45.8 %. Based on multiple regression analysis, mortality was independently associated with onco-hematological disease [odds ratio (OR) 11.7, 95 % confidence interval (CI) 1.3-104.7; p = 0.028], severe multiple organ dysfunction syndrome (MODS) (OR 5.1, 95 % CI 1.7-15; p = 0.003) and hypotension (OR 11.6, 95 % CI 1.4-93.2; p = 0.021). In the subgroup analysis, a fluid overload (FO) of more than 10 % (FO>10 %) at the beginning of CRRT seems to be a negative predictor of mortality (OR 10.9, 95 % CI 0.78-152.62; p = 0.07) only in children with milder disease (renal patients). Due to lack of statistical power, the independent effect of fluid overload on mortality could not be analyzed in all subgroups of patients., Conclusions: In children treated with CRRT the underlying diagnosis and severity of illness are independent risk factors for mortality. The degree of FO is a negative predictor only in patients with milder disease.

Angiotensin-converting enzyme inhibitors (ACEi) for renin-angiotensin-aldosterone system (RAAS) blockade are routinely used to slow CKD progression. However, vitamin D may also promote renoprotection by suppressing renin transcription through cross-talk between RAAS and vitamin D-fibroblast growth factor-23 (FGF-23)-Klotho pathways. To determine whether vitamin D levels influence proteinuria and CKD progression in children, we performed a post hoc analysis of the Effect of Strict Blood Pressure Control and ACE Inhibition on Progression of CKD in Pediatric Patients (ESCAPE) cohort. In 167 children (median eGFR 51 ml/min per 1.73 m(2)), serum 25-hydroxyvitamin D (25(OH)D), FGF-23, and Klotho levels were measured at baseline and after a median 8 months on ACEi. Children with lower 25(OH)D levels had higher urinary protein/creatinine ratios at baseline (P=0.03) and at follow-up (P=0.006). Levels of 25(OH)D and serum vitamin D-binding protein were not associated, but 25(OH)D ≤50 nmol/L associated with higher diastolic BP (P=0.004). ACEi therapy also associated with increased Klotho levels (P<0.001). The annualized loss of eGFR was inversely associated with baseline 25(OH)D level (P<0.001, r=0.32). Five-year renal survival was 75% in patients with baseline 25(OH)D ≥50 nmol/L and 50% in those with lower 25(OH)D levels (P<0.001). This renoprotective effect remained significant but attenuated with ACEi therapy (P=0.05). Renal survival increased 8.2% per 10 nmol/L increase in 25(OH)D (P=0.03), independent of eGFR; proteinuria, BP, and FGF-23 levels; and underlying renal diagnosis. In children with CKD, 25(OH)D ≥50 nmol/L was associated with greater preservation of renal function. This effect was present but attenuated with concomitant ACEi therapy., (Copyright © 2016 by the American Society of Nephrology.)

Background: In severe neonatal hyperammonemia, extracorporeal dialysis (ECD) provides higher ammonium clearance than peritoneal dialysis (PD). However, there are limited outcome data in relation to dialysis modality., Methods: Data from infants with hyperammonemia secondary to inborn errors of metabolism (IEM) treated with dialysis were collected in six Italian centers and retrospectively analyzed., Results: Forty-five neonates born between 1990 and 2011 were enrolled in the study. Of these, 23 were treated with PD and 22 with ECD (14 with continuous venovenous hemodialysis [CVVHD], 5 with continuous arteriovenous hemodialysis [CAVHD], 3 with hemodialysis [HD]). Patients treated with PD experienced a shorter duration of predialysis coma, while those treated with HD had a shorter ammonium decay time compared with all the other patients (p < 0.05). No difference in ammonium reduction rate was observed between patients treated with PD, CAVHD or CVVHD. Carbamoyl phosphate synthetase deficiency (CPS) was significantly associated with increased risk of death (OR: 9.37 [1.52-57.6], p = 0.016). Predialysis ammonium levels were significantly associated with a composite end-point of death or neurological sequelae (adjusted OR: 1.13 [1.02-1.27] per 100 μmol/l, p = 0.026). No association was found between outcome and dialysis modality., Conclusions: In this study, a delayed ECD treatment was not superior to PD in improving the short-term outcome of neonates with hyperammonemia secondary to IEM.

Background: Anterior ischemic optic neuropathy (AION) is characterized by infarction of the optic nerve head due to hypoperfusion of the posterior ciliary arteries and causes sudden blindness in adults on chronic dialysis, but has rarely been described in children. Unlike adults, children do not have comorbidities related to aging., Methods: We retrospectively analyzed data of 7 children on nocturnal continuous cycling peritoneal dialysis (CCPD) who developed AION identified within the Italian Registry of Pediatric Chronic Dialysis. We also summarized data from 10 cases reported in the literature., Results: Our 7 patients suffered from acute onset bilateral blindness. Their mean age was 3.2 years and chronic hypotension had been observed prior the AION in 3 of the 7 children. Low systolic blood pressure (SBP) was associated with higher risk of developing AION according to statistical analysis. None recovered completely. In total, 11 out of 16 experienced a partial recovery and no clear evidence emerged favoring specific treatments., Conclusions: Hypotensive children treated with CCPD are at increased risk of developing AION, which often results in irreversible blindness., (Copyright © 2015 International Society for Peritoneal Dialysis.)

This study evaluated the performance of the pediatric RIFLE (pRIFLE) score for acute kidney injury (AKI) diagnosis and prognosis after pediatric cardiac surgery. It was a single-center prospective observational study developed in a pediatric cardiac intensive care unit (pCICU) of a tertiary children's hospital. The study enrolled 160 consecutive children younger than 1 year with congenital heart diseases and undergoing cardiac surgery with cardiopulmonary bypass. Of the 160 children, 50 (31 %) were neonates, and 20 (12 %) had a univentricular heart. Palliative surgery was performed for 53 patients (33 %). A diagnosis of AKI was determined for 90 patients (56 %), and 68 (42 %) of these patients achieved an "R" level of AKI severity, 17 patients (10 %) an "I" level, and 5 patients (3 %) an "F" level. Longer cross-clamp times (p = 0.045), a higher inotropic score (p = 0.02), and a higher Risk-Adjusted Classification for Congenital Heart Surgery score (p = 0.048) but not age (p = 0.27) correlated significantly with pRIFLE class severity. Patients classified with a higher pRIFLE score required a greater number of mechanical ventilation days (p = 0.03) and a longer pCICU stay (p = 0.045). Renal replacement therapy (RRT) was needed for 13 patients (8.1 %), with two patients receiving continuous hemofiltration, and 11 patients receiving peritoneal dialysis. At the start of dialysis, the distribution of RRT patients differed significantly within pRIFLE classes (p = 0.015). All deceased patients were classified as pRIFLE "I" or "F" (p = 0.0001). The findings showed that pRIFLE is easily and feasibly applied for pediatric patients with congenital heart disease. The pRIFLE classification showed that AKI incidence in pediatric cardiac surgery infants is high and associated with poorer outcomes.

Background/aims: We hypothesized that sepsis could have an impact on the sensitivity of serum and urinary neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C (CysC) for acute kidney injury (AKI) diagnosis in critically ill children., Methods: Serum NGAL (sNGAL) and urinary NGAL (uNGAL) and CysC were measured daily in the first 48 h from pediatric intensive care unit admission in 11 consecutive critically ill children with severe sepsis; a single measurement was made in a population of 10 healthy controls undergoing minor ambulatory surgery to exclude possible biases in the laboratory methods., Results: uNGAL, serum CysC (sCysC), and urinary CysC (uCysC) levels were significantly increased in patients with septic AKI compared with septic patients without AKI, while sNGAL levels were not significantly different between septic patients with and without AKI. Median serum creatinine levels did not show significant differences between AKI and non-AKI patients., Conclusions: uNGAL, sCysC and uCysC were not altered by sepsis and were good predictors of AKI. In a septic state, sNGAL alone did not discriminate patients with AKI from those without AKI., (Copyright © 2013 S. Karger AG, Basel.)

Background: Autologous arteriovenous fistulas (AVFs) are the current gold standard for vascular access in hemodialysis (HD). However, in pediatric patients, specific clinical settings may contraindicate the procedure, thus mandating the use of a prosthetic graft (PG)., Case-Diagnosis/treatment: We report a case of successful polycarbonate urethane graft implantation and subsequent resumption of HD 12 h after the procedure in a young girl with end-stage renal disease (ESRD), challenging vascular anatomy and the absence of vascular access., Conclusions: The use of polycarbonate urethane PGs in children with ESRD and difficult vascular accesses may represent a valid alternative for early resumption of HD.

Primary hyperoxaluria Type 1 is a rare autosomal recessive inborn error of glyoxylate metabolism, caused by a deficiency of the liver-specific enzyme alanine:glyoxylate aminotransferase. The disorder results in overproduction and excessive urinary excretion of oxalate, causing recurrent urolithiasis and nephrocalcinosis. As glomerular filtration rate declines due to progressive renal involvement, oxalate accumulates leading to systemic oxalosis. The diagnosis is based on clinical and sonographic findings, urine oxalate assessment, enzymology and/or DNA analysis. Early initiation of conservative treatment (high fluid intake, pyridoxine, inhibitors of calcium oxalate crystallization) aims at maintaining renal function. In chronic kidney disease Stages 4 and 5, the best outcomes to date were achieved with combined liver-kidney transplantation.

Secondary hyperparathyroidism is a common complication of chronic renal failure. Kidney transplantation corrects renal insufficiency and most metabolic abnormalities but hyperparathyroidism persists in 50% of children after transplantation. The aim of this study was to investigate parathyroid hormone (PTH) course and potential risk factors for hyperparathyroidism in children after renal transplant. We collected data from 145 transplanted children (mean follow-up 4.7 years). Intact PTH level (iPTH) rapidly decreased in the first 6 months post-transplant and continued to decline in the following years. iPTH was above the normal range in 69.1% of the patients at the time of transplant and in 47% 1 year later, this improvement continuing thereafter. Hypercalcemia was present in 20.3% of the patients before transplant and in 6.3 and 4.1% of patients 6 months and 1 year after transplant, respectively. Hypophosphatemia was present in 5.5% of the patients at 6 months, and 45.5% of the patients needed phosphorus supplements during the first 6 months after transplant. Multivariate analysis indicated pre-transplant hyperparathyroidism, dialysis duration, creatinine clearance and hypophosphatemia as predictors of persistent hyperparathyroidism. In kidney transplanted children, serum iPTH normalized in the long term in the majority of cases. Thus, parathyroidectomy should be reserved for selected patients.

Unlabelled: Cobalamin C (Cbl-C) defect is the most common inborn error of cobalamin metabolism which causes a block in the pathway responsible for the synthesis of its two metabolically active forms methyl- and adenosylcobalamin. Cbl-C defect causes the accumulation of methylmalonic acid and homocysteine and decreased methionine synthesis. The clinical presentation of patients with early-onset Cbl-C defect, characterized by a multisystem disease with severe neurological, ocular, hematological, renal, gastrointestinal, cardiac, and pulmonary manifestations, differs considerably from what observed in the "classical" form of methylmalonic aciduria caused by defect of methylmalonyl-CoA mutase. This last condition is in most cases dominated in the neonatal period by a metabolic encephalopathy "intoxication type" with severe hyperammonemia and ketoacidosis. We report a Cbl-C defect patient presenting a neonatal encephalopathy with severe hyperammonemia and ketoacidosis who was successfully treated with peritoneal dialysis., Conclusion: To the best of our knowledge, there are no reported cases of Cbl-C defect showing an acute presentation resembling a classical methylmalonic aciduria. This observation enlarges the spectrum of inherited diseases to be considered in the differential diagnosis of neonatal hyperammonemia.

Background: Although inhibition of the renin-angiotensin system delays the progression of renal failure in adults with chronic kidney disease, the blood-pressure target for optimal renal protection is controversial. We assessed the long-term renoprotective effect of intensified blood-pressure control among children who were receiving a fixed high dose of an angiotensin-converting-enzyme (ACE) inhibitor., Methods: After a 6-month run-in period, 385 children, 3 to 18 years of age, with chronic kidney disease (glomerular filtration rate of 15 to 80 ml per minute per 1.73 m(2) of body-surface area) received ramipril at a dose of 6 mg per square meter of body-surface area per day. Patients were randomly assigned to intensified blood-pressure control (with a target 24-hour mean arterial pressure below the 50th percentile) or conventional blood-pressure control (mean arterial pressure in the 50th to 95th percentile), achieved by the addition of antihypertensive therapy that does not target the renin-angiotensin system; patients were followed for 5 years. The primary end point was the time to a decline of 50% in the glomerular filtration rate or progression to end-stage renal disease. Secondary end points included changes in blood pressure, glomerular filtration rate, and urinary protein excretion., Results: A total of 29.9% of the patients in the group that received intensified blood-pressure control reached the primary end point, as assessed by means of a Kaplan-Meier analysis, as compared with 41.7% in the group that received conventional blood-pressure control (hazard ratio, 0.65; confidence interval, 0.44 to 0.94; P=0.02). The two groups did not differ significantly with respect to the type or incidence of adverse events or the cumulative rates of withdrawal from the study (28.0% vs. 26.5%). Proteinuria gradually rebounded during ongoing ACE inhibition after an initial 50% decrease, despite persistently good blood-pressure control. Achievement of blood-pressure targets and a decrease in proteinuria were significant independent predictors of delayed progression of renal disease., Conclusions: Intensified blood-pressure control, with target 24-hour blood-pressure levels in the low range of normal, confers a substantial benefit with respect to renal function among children with chronic kidney disease. Reappearance of proteinuria after initial successful pharmacologic blood-pressure control is common among children who are receiving long-term ACE inhibition. (ClinicalTrials.gov number, NCT00221845.), (2009 Massachusetts Medical Society)

Residual renal function (RRF) has been associated with a better nutritional status in adult patients on chronic dialysis, but there is as yet no data available for young patients on chronic hemodialysis (HD). We have retrospectively analyzed 3-day dietary reports and simultaneous urea kinetic monitoring data (n = 179) of 30 children, adolescents and young adults on chronic HD. The protein catabolic rate (PCR) was calculated and normalized by body weight (nPCR). The HD dialysis dose (Kt/VHD), RRF (calculated by urea clearance, Ku, and expressed as residual Kt/V) and total Kt/V (Kt/Vtot) were evaluated. In all patients, nPCR was correlated with dietary protein intake (nDPI) (p < 0.0001) and Kt/Vtot (p < 0.0001) but not with Kt/VHD (p = 0.11). In patients with RRF, Ku was associated with nPCR (p < 0.0001), while Kt/VHD was not (p = 0.10), and nPCR was higher than in patients without RRF (1.46 +/- 0.41 vs. 1.03 +/- 0.33 g/kg/day; p < 0.0001). Patients on recombinant growth hormone (rhGH) treatment showed higher nPCR values than those without rhGH (1.34 +/- 0.41 vs. 1.01 +/- 0.39 g/kg/day; p < 0.0001). In a multiple regression model including age, rhGH treatment, RRF, Kt/Vtot and Kt/VHD, and nPCR showed the best correlation with RRF (beta = 0.128; p < 0.0001). In conclusion, in children, adolescents and young adults on chronic HD treatment, RRF positively affects nutrition independently of HD efficiency and rhGH treatment.

Primary hyperoxaluria (PH1) is a rare inborn autosomal recessive metabolic disorder due to the deficiency of hepatic alanine-glyoxylate-aminotransferase. This deficiency results in excessive synthesis and urinary excretion of oxalate, inducing renal stone formation and deposition of calcium oxalate in the kidney, bone, myocardium, and vessels (systemic oxalosis, SO) in the most severely affected individuals. We report renal and skeletal changes in a 3-month-old girl with PH1 and SO. Intense cortico-medullary hyperechogenicity and increased homogeneous radiopacity of normal-sized kidneys suggested the diagnosis of SO. Skeletal survey showed osteopenia and characteristic symmetrical metaphyseal transverse bands in long bones, progressively becoming more dense and migrating towards the diaphysis. Multiple pathological and slowly healing fractures of the limbs occurred at the dense band level. A radiopaque rim was then observed in flat bones, epiphyseal nuclei, and vertebral bodies. Inflammatory granulomatous reaction, induced by the presence of oxalate crystals in the marrow spaces, coexisted with progressively evident radiological signs of secondary hyperparathyroidism, with partially overlapping features. The patient was treated by peritoneal dialysis and hemodialysis until combined liver-kidney transplantation. There are no previous reports of infants treated with hemodialysis for more than 2 years.

The infant who develops acute kidney injury (AKI) after cardiopulmonary bypass (CPB) surgery presents unique challenges and opportunities to the clinician and to the investigator interested in the study of AKI pathophysiology. Infants do not have many of the comorbid conditions that confound CPB outcome studies of adults. Because the timing of the AKI event is known in this clinical setting, collaboration between cardiology intensivists, nephrologists, and perfusion technologists is essential to minimize the impact of CPB on the kidney. Early institution of ultrafiltration in the operating room and renal replacement therapy in the postoperative period may decrease the proinflammatory milieu and its resultant systemic effects. In addition, early initiation of renal replacement therapy to prevent fluid overload may result in improved infant outcomes.

Optimal care of the neonate with hyperammonemia requires expertise in the evaluation, medical management, and decision to initiate dialytic therapy, and therefore compels expeditious collaboration between neonatal intensive care physicians, medical geneticists, and pediatric nephrologists. Neonatal and dialysis nursing expertise also is paramount for the successful provision of dialysis therapy in this setting. The current article addresses the underlying causes, medical management strategies, and dialytic therapy considerations in caring for the neonate with hyperammonemia.

Pediatric nephrologists and critical care physicians are faced with a heterogeneous patient population with varied epidemiology caring for children with acute kidney injury or other diseases that may require renal replacement therapy provision. We have composed 4 detailed case scenarios to highlight the challenges and interdisciplinary approach required for optimal care provision to children, and that serve to direct the different articles contained in this special issue of Seminars of Nephrology devoted to acute kidney injury in children.

Increased left ventricular (LV) mass in children with chronic renal insufficiency (CRI) might be adaptive to sustain myocardial performance in the presence of increased loading conditions. It was hypothesized that in children with CRI, LV systolic function is impaired despite increased LV mass (LVM). Standard echocardiograms were obtained in 130 predialysis children who were aged 3 to 18 yr (59% boys) and had stages II through IV chronic kidney disease and in 130 healthy children of similar age, gender distribution, and body build. Systolic function was assessed by measurement of fractional shortening at the endocardial (eS) and midwall (mS) levels and computation of end-systolic stress (myocardial afterload). The patients with CRI exhibited a 6% lower eS (33.1 +/- 5.5 versus 35.3 +/- 6.1%; P < 0.05) and 10% lower mS (17.8 +/- 3.1 versus 19.7 +/- 2.7%; P < 0.001) than control subjects in the presence of significantly elevated BP, increased LVM, and more concentric LV geometry. Whereas the decreased eS was explained entirely by augmented end-systolic stress, mS remained reduced after correction for myocardial afterload. The prevalence of subclinical systolic dysfunction as defined by impaired mS was more than five-fold higher in patients with CRI compared with control subjects (24.6 versus 4.5%; P < 0.001). Systolic dysfunction was most common (48%) in patients with concentric hypertrophy and associated with lower hemoglobin levels. CRI in children is associated with impaired intrinsic LV contractility, which parallels increased LVM.

Left ventricular hypertrophy (LVH) is the most important independent marker of cardiovascular risk in adults with chronic kidney disease. Cardiovascular morbidity seems increased even in children with chronic renal insufficiency (CRI), but the age and stage of CRI when cardiac alterations become manifest are unknown. For assessing the prevalence and factors associated with abnormal LV geometry in children with CRI, echocardiograms, ambulatory BP monitoring, and biochemical profiles were obtained in 156 children aged 3 to 18 yr with stages 2 through 4 chronic kidney disease (GFR 49 +/- 19 ml/min per 1.73 m2) and compared with echocardiograms obtained in 133 healthy children of comparable age and gender. LV mass was indexed to height2.7. Concentric LV remodeling was observed in 10.2%, concentric LVH in 12.1%, and eccentric LVH in 21% of patients. LVH was more common in boys (43.3 versus 19.4%; P < 0.005). Probability of LVH independently increased with male gender (odds ratio [OR] 2.62; P < 0.05) and standardized body mass index (OR 1.56; P = 0.01). Low hemoglobin, low GFR, young age, and high body mass index were independent correlates of LV mass index (0.005 < P < 0.05). LV concentricity (relative wall thickness) was positively associated with serum albumin (P < 0.05). Probability of abnormal LV geometry increased with C-reactive protein >10 mg/dl (OR 26; P < 0.001). In conclusion, substantial cardiac remodeling of both concentric and eccentric type is present at young age and early stages of CRI in children. Prevalence of LVH is related to male gender, anemia, and ponderosity but not to BP. Additional effects of volume status and inflammation on cardiac geometry are also evident.

We have previously described severe hyperparathyroidism during the pubertal growth spurt in three uremic adolescents treated with recombinant human growth hormone (rhGH). Here we investigate the possible role of puberty in the genesis of hyperparathyroidism during rhGH treatment of a large cohort of patients. Data from 67 uremic patients treated with rhGH from five Italian pediatric nephrology centers were retrospectively recorded every 3 months starting 1 year before rhGH administration. The mean (+/-SD) rhGH treatment observation period was 19.9+/-5.9 months. The mean age at the start of rhGH treatment was 8.3+/-3.6 years. Of the 67 patients, 15 reached pubertal stage 2 during the 1st year of rhGH treatment and 12 of these 15 progressed to pubertal stage 3. The relative increase in parathyroid hormone (PTH) levels after rhGH initiation was greater in pubertal [1.95, 95% confidence interval (CI) 1.43-2.66] than in prepubertal patients (1.19, 95% CI 1.01-1.40). Increases in PTH levels were significantly different between the two groups (Delta=1.64, 95% CI 1.16-3.19, P=0.007). Multiple regression analysis showed an inverse correlation between PTH and calcium levels and a positive correlation between PTH and pubertal stage 3. There was no correlation with phosphate levels and calcitriol dosage. In conclusion, these results suggest that in uremic adolescents treated with rhGH puberty may influence PTH levels.

Objectives: We sought to investigate the effectiveness of glucocorticoid administration or continuous venovenous hemodiafiltration on endothelin and corticotropin-releasing factor release or clearance during prolonged fetal cardiac bypass and on the overall performance of fetuses., Methods: Circulating endothelin 1, 2, and 3 and corticotropin-releasing factor levels were measured in fetal ewes during a 60-minute cardiac bypass period performed with an inline axial flow pump. Blood samples were collected before, during, and 90 minutes after cardiac bypass. Animals were divided into 4 groups. The betamethasone group (n = 6) received maternal treatment with 12 mg of betamethasone 1 and 2 days before the experiment. The methylprednisolone group (n = 5) received fetal treatment with 40 mg/kg intravenous methylprednisolone at the beginning of cardiac bypass. The continuous venovenous hemodiafiltration group (n = 4) underwent continuous venovenous hemodiafiltration with a 0.3-m(2) polysulfone filter during cardiac bypass. The final group was the control group (n = 4)., Results: Maternal steroid pretreatment failed to decrease endothelin or corticotropin-releasing factor production when compared with levels in the control animals. Fetal treatment with methylprednisolone produced a significant decrease in endothelin 2 production during cardiac bypass (P <.02) and endothelin 1 production at the end of the experiment (P <.02). Continuous venovenous hemodiafiltration blocked completely the increase of endothelin and corticotropin-releasing factor levels during cardiac bypass (P <.02), which was maintained 90 minutes after cardiac bypass. Acid-base balance was preserved during cardiac bypass by the continuous venovenous hemodiafiltration but worsened after disconnection of the extracorporeal circuit, whereas animals treated with methylprednisolone had better pH, Paco(2), and bicarbonate levels by the end of the experiment. The overall tolerance of the procedure was better in the continuous venovenous hemodiafiltration group during cardiac bypass and in the methylprednisolone group at the end of the experiment., Conclusions: Continuous venovenous hemodiafiltration provides sustained stability of endothelin levels during fetal cardiac bypass. This technique might help, in association with fetal steroid treatment, to contain the inflammatory response leading to postbypass placental dysfunction.