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Pediatric chronic kidney disease (CKD) is characterized by many co-morbidities, including impaired growth and development, CKD-mineral and bone disorder, anemia, dysregulated iron metabolism, and cardiovascular disease. In pediatric CKD cohorts, higher circulating concentrations of fibroblast growth factor 23 (FGF23) are associated with some of these adverse clinical outcomes, including CKD progression and left ventricular hypertrophy. It is hypothesized that lowering FGF23 levels will reduce the risk of these events and improve clinical outcomes. Reducing FGF23 levels in CKD may be accomplished by targeting two key stimuli of FGF23 production-dietary phosphate absorption and iron deficiency. Ferric citrate is approved for use as an enteral phosphate binder and iron replacement product in adults with CKD. Clinical trials in adult CKD cohorts have also demonstrated that ferric citrate decreases circulating FGF23 concentrations. This review outlines the possible deleterious effects of excess FGF23 in CKD, summarizes data from the adult CKD clinical trials of ferric citrate, and presents the Ferric Citrate and Chronic Kidney Disease in Children (FIT4KiD) study, a randomized, placebo-controlled trial to evaluate the effects of ferric citrate on FGF23 in pediatric patients with CKD stages 3-4 (ClinicalTrials.gov Identifier NCT04741646).

Author(s): Amy J. Kogon [sup.1] , Lance S. Ballester [sup.2] , Jarcy Zee [sup.3] , Natalie Walker [sup.1] , Joshua J. Zaritsky [sup.4] , Meredith A. Atkinson [sup.5] , Christine [...], Background Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects. Methods Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio [greater than or equal to] 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration. Results Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001). Conclusion Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown. Clinical trial NCT01835639. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Background In its first 3 years, the Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative demonstrated a statistically significant increase in the likelihood of compliance with a standardized follow-up care bundle and a significant reduction in peritonitis. We sought to determine if compliance with care bundles and low peritonitis rates could be sustained in centers continuously participating for 84 months. Methods Centers that participated from collaborative launch through the 84-month study period and provided pre-launch peritonitis rates were included. Children on maintenance peritoneal dialysis were eligible for enrollment. Changes in bundle compliance were assessed using a logistic regression model or a generalized linear mixed model (GLMM). Changes in average annualized peritonitis rates over time were modeled using GLMMs. Results Nineteen centers contributed 1055 patients with 1268 catheters and 17,247 follow-up encounters. The likelihood of follow-up compliance increased significantly over the study period (OR 1.05 95% confidence interval (CI) 1.03, 1.07; p < 0.001). Centers achieved [greater than or equal to] 80% follow-up bundle compliance by 28 months and maintained a mean compliance of 84% between 28 and 84 months post-launch. Average monthly peritonitis rates decreased from 0.53 (95% CI 0.37, 0.70) infections per patient-year pre-launch to 0.30 (95% CI 0.23, 0.43) at 84 months post-launch, p < 0.001. Conclusions Centers participating in the SCOPE Collaborative for 84 months achieved and maintained a high level of compliance with a standardized follow-up care bundle and demonstrated a significant and continued reduction in average monthly peritonitis rates. Graphical abstract, Author(s): Alicia M. Neu [sup.1] , Troy Richardson [sup.2] , Heidi Gruhler De Souza [sup.2] , Allison Redpath Mahon [sup.3] , Mahima Keswani [sup.4] , Joshua Zaritsky [sup.5] , Raj [...]

Ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) particle that is FDA-approved for parenteral treatment of iron deficiency anemia in adults with chronic kidney disease. Because of the association between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with severe chronic kidney disease, we sought to evaluate the diagnostic role of ferumoxytol-enhanced MR venography in children with chronic kidney disease. Twenty children underwent 22 high-resolution ferumoxytol-enhanced MR venography examinations at 3.0 T. High-resolution 3-D contrast-enhanced imaging was performed at a minimum of 3 time points following injection of ferumoxytol at a total dose of 4 mg/kg. Two blinded pediatric radiologists independently scored six named veins on ferumoxytol-enhanced MR venography examinations according to a three-point subjective score, where a score ≥2 was considered diagnostic. Additionally, all relevant venous structures in the included field of view were analyzed for occlusive or non-occlusive thrombosis, compression and presence of collaterals. All patients underwent ferumoxytol-enhanced MR venography successfully and without adverse event. The overall scores of the reviewing radiologists for all venous structures were 2.7-2.9. In all cases, the reviewers were confident basing their diagnoses on the ferumoxytol-enhanced MR venography findings. In 12 of 22 examinations, findings on follow-up imaging or invasive procedures were available to correlate with the findings on ferumoxytol-enhanced MR venography. There was complete concordance between the findings from follow-up imaging and invasive procedures with findings from ferumoxytol-enhanced MR venography. Ferumoxytol holds promise as a powerful alternative to gadolinium-based contrast agents for reliable, high-resolution MR venography in children with chronic kidney disease.

Outcomes for pediatric SBT patients requiring perioperative RRT in the PICU remain unknown. The objectives were to document our center's experience with PICU SBT patients receiving perioperative RRT and to identify variables predictive of survival to discharge. A retrospective chart review of patients (ages, 0-18 yr) between January 1, 2000 and December 31, 2011 that received RRT within a SBT perioperative period and were transplanted at our university-affiliated, tertiary care children's hospital was performed. Six SBT patients received perioperative RRT (ages, 5-12 yr). Three patients (50%) survived to hospital discharge. Among survivors, RRT was required for a total of 1-112 days (mean, 49.7 days). All three survivors survived to hospital discharge without renal transplantation and free of RRT. There was a trend toward increased survival among older patients receiving RRT (p = 0.05). Survivors had a higher I-125 GFR prior to PICU admission (p = 0.045). A higher I-125 GFR prior to PICU admission among survivors may support this test's utility during SBT evaluation. In our experience, a high survival rate and freedom from RRT at the time of discharge support RRT use in the SBT population.

BackgroundExposure to gadolinium-based contrast agents (GBCA) in patients with chronic kidney disease (CKD) has been associated with the development of a potentially fatal disorder, nephrogenic systemic fibrosis (NSF). Although contrast-enhanced computed tomography (CT) is an alternative to magnetic resonance imaging (MRI), it carries the risk of radiation exposure and further reduction of residual renal function. Therefore we sought to assess the feasibility of ferumoxytol as an alternative to GBCA for contrast-enhanced MR angiography (MRA) in a pediatric cohort with CKD. Ferumoxytol is a parenteral iron supplement that contains ultrasmall superparamagnetic iron oxide (USPIO) and is a potent relaxivity agent for MRI.MethodsWe describe the MRI findings in ten pediatric patients who needed detailed vascular mapping. Ferumoxytol (4 mg/kg) was administered intravenously for contrast-enhanced MRA. The patients tolerated the procedure without complications.ResultsResulting studies were highly diagnostic and were pivotal in guiding patient management. The images were notable for clear delineation of multiple vascular occlusions.ConclusionsGiven the concerns associated with the use of GBCAs in renal failure, ferumoxytol is an excellent alternative contrast agent in pediatric end stage renal disease (ESRD) patients. Future studies are needed in order to further evaluate safety and efficacy of ferumoxytol in this patient population.

Introduction: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. Objective: FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. Design: FIONA (NCT05196035; Eudra-CT: 2021–002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021–002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. Conclusion: FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. Trial registration: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022. [ABSTRACT FROM AUTHOR]

Background Children who were born prematurely, those with a very low birthweight, or who have survived the neonatal intensive care unit (NICU) are at risk for the development of hypertension and chronic kidney disease (CKD), and thus require blood pressure screening less than 3 years of age, per American Academy of Pediatrics (AAP) 2004 and 2017 guidelines. Methods We reviewed the practice patterns of a large pediatric health care system and assessed adherence to the AAP clinical practice guidelines on blood pressure measurements in children less than 3 years of age for hypertension and CKD with the following risk factors: prematurity, very low birthweight, and a neonatal intensive care setting encounter. This retrospective chart review included a total of 9965 patients with a median gestational age of 34 weeks. Results Overall, 38% of patients had at least one blood pressure measured less than 3 years of age. Primary care accounted for 41% of all outpatient encounters and 4% of all blood pressure measurements. Surgical specialties (i.e., ophthalmology, otolaryngology, and orthopedics) accounted for many non-primary care visits and were less likely than medical specialties (i.e., cardiology and nephrology) to obtain a blood pressure measurement (p < 0.0001). Conclusions This study of a large healthcare system's practice revealed a lack of basic screening for hypertension in a population known to be at risk for hypertension and CKD., Author(s): Lokesh Shah [sup.1] , Jobayer Hossain [sup.2] , Shirlly Xie [sup.3] , Joshua Zaritsky [sup.2] Author Affiliations: (Aff1) 0000 0001 0680 8770, grid.239552.a, Children's Hospital of Philadelphia, , 3401 [...]

Background Iron deficiency is a common cause of anemia in pediatric patients with hemodialysis-dependent chronic kidney disease (CKD-5HD). Ferric pyrophosphate citrate (FPC, Triferic®) donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Administration of FPC via dialysate or intravenously (IV) may provide a suitable therapeutic option to current IV iron preparations for these patients. Methods The pharmacokinetics and safety of FPC administered via dialysate and IV to patients aged < 6 years (n = 3), 6 to < 12 years (n = 4), and 12 to Results Mean serum total iron concentrations peaked 3 to 4 h after administration via dialysate and 2 to 4 h after IV administration and returned to baseline by 10 h after the start of hemodialysis for both routes. Iron exposure was greater after administration via dialysate than after IV administration. The absolute amount of absorbed iron after administration via dialysate roughly doubled with increasing age, but the weight-normalized amount of absorbed iron was relatively constant across age groups (~ 0.06-0.10 mg/kg). FPC was well tolerated in the small number of patients studied. Conclusions FPC iron can be administered to pediatric patients with CKD-5HD via dialysate or by the IV route. Further study of FPC administered to maintain hemoglobin concentration is indicated., Author(s): Raymond D. Pratt [sup.1] , Sarah Grimberg [sup.1] , Joshua J. Zaritsky [sup.2] , Bradley A. Warady [sup.3] Author Affiliations: (Aff1) Rockwell Medical, Inc., , 30142 Wixom Rd, Wixom, [...]

Context and implementation approaches can impede the spread of patient safety interventions. The objective of this article is to characterize factors associated with improved outcomes among 9 hospitals implementing a medication safety intervention. Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a pharmacist-driven intervention that led to a sustained reduction in nephrotoxic medication-associated acute kidney injury (NTMx-AKI) at 1 hospital. Using qualitative comparative analysis, the team prospectively assessed the association between context and implementation factors and NTMx-AKI reduction during NINJA spread to 9 hospitals. Five hospitals reduced NTMx-AKI. These 5 had either (1) a pharmacist champion and >2 pharmacists working on NINJA (Scon 1.0, Scov 0.8) or (2) a nephrologist-implementing NINJA with minimal competing organizational priorities (Scon 1.0, Scov 0.2). Interviews identified ways NINJA team leaders obtained pharmacist support or successfully implemented without that support. In conclusion, these findings have implications for future spread of NINJA and suggest an approach to study spread of safety interventions more broadly. [ABSTRACT FROM AUTHOR]

Background Maintenance peritoneal dialysis (PD) is the dialysis modality of choice for infants and young children. However, there are limited outcome data for those who undergo PD catheter insertion and initiate maintenance PD within the first year of life. Methods Using data from the Children's Hospital Association's Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (ESRD) Collaborative (SCOPE), we examined peritonitis rates and patient survival in 156 infants from 29 North American pediatric dialysis centers who had a chronic PD catheter placed prior to their first birthday. Results In-hospital and overall annualized rates of peritonitis were 1.73 and 0.76 episodes per patient-year, respectively. Polycystic kidney disease was the most frequent renal diagnosis and pulmonary hypoplasia the most common co-morbidity in infants with peritonitis. Multivariable regression models demonstrated that nephrectomy at or prior to PD catheter placement and G-tube insertion after catheter placement were associated with a nearly sixfold and nearly threefold increased risk of peritonitis, respectively. Infants with peritonitis had longer initial hospital stays and lower overall survival (86.3 vs. 95.6%, respectively; P < 0.02) than those without an episode of peritonitis. Conclusions In this large cohort of infants with ESRD, the frequency of peritonitis was high and several risk factors associated with the development of peritonitis were identified. Given that peritonitis was associated with a longer duration of initial hospitalization and increased mortality, increased attention to the potentially modifiable risk factors for infection is needed., Author(s): Joshua Jacob Zaritsky [sup.1] , Coral Hanevold [sup.2] , Raymond Quigley [sup.3] , Troy Richardson [sup.4] , Cynthia Wong [sup.5] , Jennifer Ehrlich [sup.6] , John Lawlor [sup.4] , [...]

Background: Ambulatory blood pressure monitoring (ABPM) is a standard screening tool for the diagnosis of hypertension in children, adolescents, and adults. However, there is confusion and misunderstanding about which guidelines can provide the most accurate diagnostic values. Local problem: At a large, free-standing pediatric hospital, ABPM testing was historically being conducted by both nephrology and cardiology departments. The nephrology service was using the American Heart Association (AHA) guidelines, published in 2014 for interpretation of results and for diagnosis of hypertension, whereas the cardiology service depended on the 2004 National High Blood Pressure Education Program (NHBEP) fourth report, which led to discrepancies in diagnosis of hypertension in this patient population. Methods: A nurse practitioner–led quality improvement project was designed and implemented to determine the best method of ABPM monitoring and test interpretation based on comparing results of patients using height, gender, and application of either the 2004 NHBEP fourth report or 2014 AHA guidelines. Interventions: Using a retrospective chart review, ABPM monitoring results from both cardiology and nephrology services were reviewed and compared to identify the most accurate methods and to recommend changes to practice. Results: Accuracy of interpretation for ABPM is best accomplished using the 2014 AHA guidelines. Conclusions: Using a single method of interpretation provides consistent diagnosis and treatment of hypertension in children. Nurse practitioners can apply this knowledge in other settings to manage hypertension and provide similar services in different settings, including primary care. [ABSTRACT FROM AUTHOR]