Hyperparathyroidism Is an Independent Risk Factor for Allograft Dysfunction in Pediatric Kidney Transplantation

Allograft outcome; Hyperparathyroidism; Kidney transplantationResultado del aloinjerto; Hiperparatiroidismo; Trasplante de riñónResultat de l'aloempelt; Hiperparatiroïdisme; Trasplantament de ronyóIntroduction Little is known about the consequences of deranged chronic kidney disease–mineral and bone disorder (CKD-MBD) parameters on kidney allograft function in children. We examined a relationship between these parameters over time and allograft outcome. Methods This registry study from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) collected data at baseline, months 1, 3, 6, 9, and 12 after transplant; and every 6 months thereafter up to 5 years. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤30 ml/min per 1.73 m2 or a ≥50% decline from eGFR at month 1 posttransplant was performed. Associations of parathyroid hormone (PTH), calcium, phosphate, and 25-hydroxyvitamin D (25(OH)D) with allograft outcome were investigated using conventional stratified Cox proportional hazards models and further verified with marginal structural models with time-varying covariates. Results We report on 1210 patients (61% boys) from 16 European countries. The composite end point was reached in 250 grafts (21%), of which 11 (4%) were allograft losses. In the conventional Cox proportional hazards models adjusted for potential confounders, only hyperparathyroidism (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.82–4.74) and hyperphosphatemia (HR, 1.94; 95% CI, 1.28–2.92) were associated with the composite end point. Marginal structural models showed similar results for hyperparathyroidism (HR, 2.74; 95% CI, 1.71–4.38), whereas hyperphosphatemia was no longer significant (HR, 1.35; 95% CI, 0.87–2.09), suggesting that its association with graft dysfunction can be ascribed to a decline in eGFR. Conclusion Hyperparathyroidism is a potential independent risk factor for allograft dysfunction in children.This study was supported by a research grant from the European Society for Paediatric Nephrology to AP. The authors gratefully acknowledge the funding of the Cooperative European Paediatric Renal Transplant Initiative Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology, and the German Society for Paediatric Nephrology and by grants from the pharmaceutical companies Astellas and Novartis

Computational investigation of the haemodynamics shows criticalities of central venous lines used for chronic haemodialysis in children

Background: Haemodialysis is a life-saving treatment for children with kidney failure. The majority of children have haemodialysis through central venous lines (CVLs). The use of CVLs in pediatric patients is often associated to complications which can lead to their replacement. The aim of this study is to investigate haemodynamics of pediatric CVLs to highlight the criticalities of different line designs. Methods: Four models of CVLs for pediatric use were included in this study. The selected devices varied in terms of design and sizes (from 6.5 Fr to 14 Fr). Accurate 3D models of CVLs were reconstructed from high-resolution images including venous and arterial lumens, tips and side holes. Computational fluid dynamics (CFD) analyses were carried out to simulate pediatric working conditions of CVLs in ideal and anatomically relevant conditions. Results: The arterial lumens of all tested CVLs showed the most critical conditions with the majority of blood flowing through the side-holes. A zone of low flow was identified at the lines' tip. The highest shear stresses distribution (>10 Pa) was found in the 8 Fr line while the highest platelet lysis index in the 10 Fr model. The analysis on the anatomical geometry showed an increase in wall shear stress measured in the 10 F model compared to the idealised configuration. Similarly, in anatomical models an increased disturbance and velocity of the flow was found inside the vein after line placement. Conclusion: This study provided a numerical characterization of fluid dynamics in pediatric CVLs highlighting performance criticalities (i.e. high shear stresses and areas of stagnation) associated to specific sizes (8 Fr and 10 Fr) and conditions (i.e. anatomical test)

Vitamin D prescribing in children in UK primary care practices:a population-based cohort study

OBJECTIVE: To examine temporal changes in the incidence and patterns of vitamin D supplementation prescribing by general practitioners (GPs) between 2008 and 2016. DESIGN: Population-based cohort study. SETTING: UK general practice health records from The Health Improvement Network. PARTICIPANTS: Children aged 0 to 17 years who were registered with their general practices for at least 3 months. OUTCOME MEASURES: Annual incidence rates of vitamin D prescriptions were calculated, and rate ratios were estimated using multivariable Poisson regression to explore differences by sociodemographic factors. Data on the type of supplementation, dose, dosing schedule, linked 25-hydroxyvitamin D (25(OH)D) laboratory test results and clinical symptoms suggestive of vitamin D deficiency were analysed. RESULTS: Among 2 million children, the crude annual incidence of vitamin D prescribing increased by 26-fold between 2008 and 2016 rising from 10.8 (95% CI: 8.9 to 13.1) to 276.8 (95% CI: 264.3 to 289.9) per 100 000 person-years. Older children, non-white ethnicity and general practices in England (compared with Wales/Scotland/Northern Ireland) were independently associated with higher rates of prescribing. Analyses of incident prescriptions showed inconsistent supplementation regimens with an absence of pre-supplementation 25(OH)D concentrations in 28.7% to 56.4% of prescriptions annually. There was an increasing trend in prescribing at pharmacological doses irrespective of 25(OH)D concentrations, deviating in part from UK recommendations. Prescribing at pharmacological doses for children with deficient status increased from 3.8% to 79.4%, but the rise was also observed in children for whom guidelines recommended prevention doses (0% to 53%). Vitamin D supplementation at pharmacological doses was also prescribed in at least 40% of children with no pre-supplementation 25(OH)D concentrations annually. CONCLUSIONS: There has been a marked and sustained increase in vitamin D supplementation prescribing in children in UK primary care. Our data suggests that national guidelines on vitamin D supplementation for children are not consistently followed by GPs

Delivery of a nutritional prescription by enteral tube feeding in children with chronic kidney disease stages 2-5 and on dialysis-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

The nutritional prescription (whether in the form of food or liquid formulas) may be taken orally when a child has the capacity for spontaneous intake by mouth, but may need to be administered partially or completely by nasogastric tube or gastrostomy device ("enteral tube feeding"). The relative use of each of these methods varies both within and between countries. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, has developed clinical practice recommendations (CPRs) based on evidence where available, or on the expert opinion of the Taskforce members, using a Delphi process to seek consensus from the wider community of experts in the field. We present CPRs for delivery of the nutritional prescription via enteral tube feeding to children with chronic kidney disease stages 2-5 and on dialysis. We address the types of enteral feeding tubes, when they should be used, placement techniques, recommendations and contraindications for their use, and evidence for their effects on growth parameters. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgement. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.Peer reviewe

SP890VENTRICULO-PERITONEAL SHUNTS IN CHILDREN ON HEMODIALYSIS: A SURVEY OF THE EUROPEAN PAEDIATRIC DIALYSIS WORKING GROUP (EPDWG)

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Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis

Introduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged &gt;3 years, its efficacy and safety for children aged &lt;3 years is unknown. Methods: We identified 26 children aged &lt;3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. Results: Median (interquartile range) age at the start of cinacalcet was 18 (interquartile range: 11–27) months, serum parathyroid hormone (PTH) was 792 (411–1397) pg/ml, corresponding to 11.6 (5.9–19.8) times the upper limit of normal (ULN). Serum calcium was 2.56 (2.43–2.75) mmol/l, and serum phosphate 1.47 (1.16–1.71) mmol/l. Serum 25-OH vitamin D (25–OHD) was 70 (60–89) nmol/l, 3 children were vitamin D deficient (&lt;50 nmol/l). The initial cinacalcet dose was 0.4 (0.2–0.8) mg/kg/d and the maximum dose was 1.1 (0.6–1.2) mg/kg/d. The median follow-up under cinacalcet was 1.2 (0.7–2.0) years. PTH decreased to 4.3 (2.2–7.8) times the ULN after 6 months, to 2.0 (1.0–5.3) times ULN after 12 months, and to 1.6 (0.5–3.4) times thereafter (P = 0.017/0.003/&lt;0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes &lt;2.10 mmol/l. Oral calcium intake was 84% (66%–117%) of recommended nutrient intake at start, 100% (64%–142%) at 3 months and declined to 78% (65%–102%) at 12 months of therapy. Three children developed clinical signs of precocious puberty.Conclusion: Cinacalcet efficiently controlled severe sHPT in children aged &lt;3 years and was associated with hypocalcemic episodes (similar to what is observed in older children) and precious puberty, thereby mandating meticulous control of calcium (considering nutrition, supplementation, and dialysate) and endocrine changes.</p

Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis

Introduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged &gt;3 years, its efficacy and safety for children aged &lt;3 years is unknown. Methods: We identified 26 children aged &lt;3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. Results: Median (interquartile range) age at the start of cinacalcet was 18 (interquartile range: 11–27) months, serum parathyroid hormone (PTH) was 792 (411–1397) pg/ml, corresponding to 11.6 (5.9–19.8) times the upper limit of normal (ULN). Serum calcium was 2.56 (2.43–2.75) mmol/l, and serum phosphate 1.47 (1.16–1.71) mmol/l. Serum 25-OH vitamin D (25–OHD) was 70 (60–89) nmol/l, 3 children were vitamin D deficient (&lt;50 nmol/l). The initial cinacalcet dose was 0.4 (0.2–0.8) mg/kg/d and the maximum dose was 1.1 (0.6–1.2) mg/kg/d. The median follow-up under cinacalcet was 1.2 (0.7–2.0) years. PTH decreased to 4.3 (2.2–7.8) times the ULN after 6 months, to 2.0 (1.0–5.3) times ULN after 12 months, and to 1.6 (0.5–3.4) times thereafter (P = 0.017/0.003/&lt;0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes &lt;2.10 mmol/l. Oral calcium intake was 84% (66%–117%) of recommended nutrient intake at start, 100% (64%–142%) at 3 months and declined to 78% (65%–102%) at 12 months of therapy. Three children developed clinical signs of precocious puberty.Conclusion: Cinacalcet efficiently controlled severe sHPT in children aged &lt;3 years and was associated with hypocalcemic episodes (similar to what is observed in older children) and precious puberty, thereby mandating meticulous control of calcium (considering nutrition, supplementation, and dialysate) and endocrine changes.</p

Nutritional management of the infant with chronic kidney disease stages 2-5 and on dialysis

The nutritional management of children with chronic kidney disease (CKD) is of prime importance in meeting the challenge of maintaining normal growth and development in this population. The objective of this review is to integrate the Pediatric Renal Nutrition Taskforce clinical practice recommendations for children with CKD stages 2-5 and on dialysis, as they relate to the infant from full term birth up to 1 year of age, for healthcare professionals, including dietitians, physicians, and nurses. It addresses nutritional assessment, energy and protein requirements, delivery of the nutritional prescription, and necessary dietary modifications in the case of abnormal serum levels of calcium, phosphate, and potassium. We focus on the particular nutritional needs of infants with CKD for whom dietary recommendations for energy and protein, based on body weight, are higher compared with children over 1 year of age in order to support both linear and brain growth, which are normally maximal in the first 6 months of life. Attention to nutrition during infancy is important given that growth is predominantly nutrition dependent in the infantile phase and the growth of infants is acutely impaired by disruption to their nutritional intake, particularly during the first 6 months. Inadequate nutritional intake can result in the failure to achieve full adult height potential and an increased risk for abnormal neurodevelopment. We strongly suggest that physicians work closely with pediatric renal dietitians to ensure that the infant with CKD receives the best possible nutritional management to optimize their growth and development.Peer reviewe

Energy and protein requirements for children with CKD stages 2-5 and on dialysis-clinical practice recommendations from the Pediatric Renal Nutrition Taskforce

Dietary management in pediatric chronic kidney disease (CKD) is an area fraught with uncertainties and wide variations in practice. Even in tertiary pediatric nephrology centers, expert dietetic input is often lacking. The Pediatric Renal Nutrition Taskforce (PRNT), an international team of pediatric renal dietitians and pediatric nephrologists, was established to develop clinical practice recommendations (CPRs) to address these challenges and to serve as a resource for nutritional care. We present CPRs for energy and protein requirements for children with CKD stages 2-5 and those on dialysis (CKD2-5D). We address energy requirements in the context of poor growth, obesity, and different levels of physical activity, together with the additional protein needs to compensate for dialysate losses. We describe how to achieve the dietary prescription for energy and protein using breastmilk, formulas, food, and dietary supplements, which can be incorporated into everyday practice. Statements with a low grade of evidence, or based on opinion, must be considered and adapted for the individual patient by the treating physician and dietitian according to their clinical judgment. Research recommendations have been suggested. The CPRs will be regularly audited and updated by the PRNT.Peer reviewe