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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.sup.2, 7.9 ± 3.3 ml/min/1.73 m.sup.2 and 5.5 ± 1.5 ml/min/1.73 m.sup.2 compared to conventional PD with values of 4.3 ± 1.68 ml/min/1.73 m.sup.2, 3.57 ± 1.3 ml/min/1.73 m.sup.2 and 2.53 ± 0.85 ml/min/1.73 m.sup.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. Graphical abstract, Author(s): Peter Nourse [sup.1] , Mignon McCulloch [sup.1] , Ashton Coetzee [sup.1] , Tim Bunchman [sup.2] , Stefano Picca [sup.3] , Jody Rusch [sup.4] , Andre Brooks [sup.5] , Hilton [...]

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., Author(s): Lara de Galasso [sup.1] , Stefano Picca [sup.1] , Isabella Guzzo [sup.1] Author Affiliations: (1) grid.414125.7, 0000 0001 0727 6809, Division of Nephrology and Dialysis, Department of Pediatrics, Bambino [...]

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 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 [greater than or equal to]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, Author(s): Fabio Paglialonga[sup.1] , Silvia Consolo[sup.1] , Carmine Pecoraro[sup.2] , Enrico Vidal[sup.3] , Bruno Gianoglio[sup.4] , Flora Puteo[sup.5] , Stefano Picca[sup.6] , Maria Teresa Saravo[sup.2] , Alberto Edefonti[sup.1] , Enrico [...]

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., Author(s): Lara de Galasso[sup.1] , Francesco Emma[sup.2] , Stefano Picca[sup.2] , Matteo Di Nardo[sup.3] , Emanuele Rossetti[sup.3] , Isabella Guzzo[sup.2] Author Affiliations: (1) Nephrology and Dialysis A Unit, 'Sapienza' University [...]

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 [mu]mol/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. Electronic supplementary material The online version of this article (doi:10.1007/s00467-014-2945-x) contains supplementary material, which is available to authorized users, Author(s): Stefano Picca[sup.1] , Carlo Dionisi-Vici[sup.2] , Andrea Bartuli[sup.3] , Tommaso De Palo[sup.4] , Francesco Papadia[sup.5] , Giovanni Montini[sup.6] , Marco Materassi[sup.7] , Maria Alice Donati[sup.8] , Enrico Verrina[sup.9] , [...]

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. [ABSTRACT FROM AUTHOR]

The article discusses 2 cases of infants treated with Continuous Venovenous Hemodialysis (CVVHD) following accidental ingestion of boric-acid-saturated water to prepare milk formula. One infant showed moderate dehydration, prolonged capillary refill time and tachypnea and the other infant was treated with intravenous fluids to induce forced diuresis. CVVHD was started 14 and 21 hours after last ingestion respectively considering the elevated amount of boric acid ingested in both patients.

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 m2 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.) N Engl J Med 2009;361:1639-50. [ABSTRACT FROM AUTHOR]

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.)

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/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.)

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.