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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. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B-containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome-associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently-developed anti-PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome. [ABSTRACT FROM AUTHOR]

Background The utilization of short-term daily hemodialysis has increased over the last few years, but little is known on its effects on the control of serum phosphate and fibroblast growth factor 23 (FGF23) levels. Methods We therefore performed a cross-sectional study to compare FGF23 levels as well as other biochemical variables between 24 patients undergoing short daily hemodialysis using the NxStage System® and 54 patients treated with conventional in-center hemodialysis. FGF23 levels were measured using the second-generation Immutopics® C-terminal assay. Results Short daily hemodialysis patients were younger than patients on conventional hemodialysis but there were no differences between groups in the duration of end-stage renal disease nor in the number of patients with residual renal function. A greater number of short daily hemodialysis patients received vitamin D sterol therapy than did conventional in-center hemodialysis patients while there were no differences in the use of different phosphate binders and calcimimetic therapy between groups. Overall serum calcium, phosphorus and intact parathyroid hormone levels were similar between groups. While serum phosphorus levels correlated with FGF23 concentrations in each group separately [r = 0.522 (P < 0.01) and r = 0.42 (P < 0.01) in short daily and conventional in-center hemodialysis, respectively], FGF23 levels were lower [823 RU/mL (263, 2169)] in the patients receiving short daily hemodialysis than in patients treated with conventional hemodialysis [2521 RU/mL (909, 5556)] (P < 0.01 between groups). Conclusions These findings demonstrate that FGF23 levels are significantly lower in short daily hemodialysis patients and suggest that FGF23 levels may be a more sensitive biomarker of cumulative phosphate burden than single or multiple serum phosphorus determinations in patients treated with hemodialysis. [ABSTRACT FROM AUTHOR]

Current data demonstrate pediatric patients who remain on hemodialysis (HD) therapy are more likely to be dialyzed via central venous catheters (CVCs) than arteriovenous grafts (AVGs) and fistulae (AVFs). We retrospectively compared complications and health-related quality of life (HRQOL) associated with different vascular access types at two large centers over a 1-year period. Patients included in the study were younger than 25 years of age, weighed >20 kg, and had received HD for at least 3 months. Thirty CVC patients and 21 AVG/AVF patients received a total of 2,393 and 3,506 HD treatments, respectively. The infectious complication rate was higher for CVC patients, who were hospitalized 3.7 days for each 100 HD treatments versus 0.2 days for AVG/AVF patients ( p < 0.01). CVC patients also had a much higher rate of access revision, needing 2.7 hospital days every 100 HD treatments compared with 0.2 days for AVG/AVF patients ( p < 0.01). HRQOL scores did not differ between groups. Thus, despite similar HRQOL, CVCs were associated with more complications and greater morbidity when compared with AVG/AVFs. These findings further emphasize the need to use AVG/AVFs as primary HD access for pediatric patients expected to receive a long course of maintenance HD. [ABSTRACT FROM AUTHOR]

Control of serum phosphorus remains a vexing problem in chronic kidney disease. Although novel dialysis regimens may provide excellent phosphorus control, phosphate binders remain necessary for most dialysis patients. Block et al. present a phase I clinical trial examining the safety and efficacy of SBR759, a novel non-calcium, iron-based phosphate binder. Although the risks of iron accumulation and hypocalcemia must be addressed, this phosphate binder appears to be well tolerated and effective and offers a powder-based formulation. [ABSTRACT FROM AUTHOR]

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: Genetic testing is at the forefront of medical diagnosis, management, and preventative care particularly within the field of nephrology, but such testing can be prohibitively expensive for patients from disadvantaged backgrounds. This study is aimed at exploring how use of a low-cost, comprehensive commercial panel could increase availability of genetic testing to patients served by an inner-city American hospital and overcome many of the obstacles faced by these patients, including lack of availability of pediatric geneticist and genetic counselors, leading to delay in care and management, cost of genetic testing, and inaccessibility of genetic testing to underserved populations. Methods: Single-center retrospective analysis patients who underwent genetic testing with NATERA Renasight Kidney Gene Panels run between November 2020 and October 2021. Results: Genetic testing was offered to 208 patients, with 193 tests performed, 10 pending, and 4 deferred. Seventy-six patients were found to have results of clinical significance; 117 patients were found to have a negative result, of which 79 were found to have a variant of unknown significance (VUS); and 8 of these 79 VUS were later determined to be clinically significant leading to a change in management. Patient payment data breakdown showed that of 173, 68% used public insurance coverage, 27% used commercial or private insurance, and 5% were unknown. Conclusions: Genetic testing with the NATERA Renasight Panel provided a high positivity rate for genetic testing using next generation sequencing. It also allowed us to provide access to genetic testing to a larger population, specifically underserved and underrepresented patients. [ABSTRACT FROM AUTHOR]

This corrects the article DOI: 10.1038/nrneph.2017.155. [ABSTRACT FROM AUTHOR]

Background: Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC). Methods: This retrospective multicenter cross-sectional study was conducted on children ≤ 21 years old with NL/NC from pediatric nephrology/urology centers that underwent the Invitae Nephrolithiasis Panel 1/1/2019–9/30/2021. The diagnostic yield of the genetic panel was calculated. Bivariate and multiple logistic regression were performed to assess for predictors of positive genetic testing. Results: One hundred and thirteen children (83 NL, 30 NC) from 7 centers were included. Genetic testing was positive in 32% overall (29% NL, 40% NC) with definite diagnoses (had pathogenic variants alone) made in 11.5%, probable diagnoses (carried a combination of pathogenic variants and variants of uncertain significance (VUS) in the same gene) made in 5.4%, and possible diagnoses (had VUS alone) made in 15.0%. Variants were found in 28 genes (most commonly HOGA1 in NL, SLC34A3 in NC) and 20 different conditions were identified. Compared to NL, those with NC were younger and had a higher proportion with developmental delay, hypercalcemia, low serum bicarbonate, hypophosphatemia, and chronic kidney disease. In multivariate analysis, low serum bicarbonate was associated with increased odds of genetic diagnosis (β 2.2, OR 8.7, 95% CI 1.4–54.7, p = 0.02). Conclusions: Genetic testing was high-yield with definite, probable, or possible explanatory variants found in up to one-third of children with NL/NC and shows promise to improve clinical practice. [ABSTRACT FROM AUTHOR]

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 <18 years (n = 15) were investigated in a multicenter, open-label, two-period, single-dose study. FPC (0.07 mg iron/kg) was infused IV into the venous blood return line during hemodialysis session no. 1. FPC iron was added to bicarbonate concentrate to deliver 2 μM (110 μg/L) iron via dialysate during hemodialysis session no. 2.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. [ABSTRACT FROM AUTHOR]

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 ≥ 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 < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 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. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Plasma hepcidin levels are elevated but responsive to erythropoietin therapy in renal disease," by D. R. Ashby and colleagues.

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]

Background Protein-energy wasting, inflammation and refractory anemia are common in long-term hemodialysis patients. A decreased responsiveness to erythropoiesis-stimulating agents (ESA) is often the cause of the refractory anemia. We hypothesized that the malnutrition–inflammation complex is an independent predictor of decreased responsiveness to ESAs in hemodialysis patients. Methods This cohort study of 754 hemodialysis patients was examined for an association between inflammatory and nutritional markers, including the malnutrition–inflammation score (MIS) and responsiveness to ESA. Cubic spline models were fitted to verify found associations. Results The mean (±SD) age of patients was 54 ± 15 years, 53% were diabetic and 32% blacks. MIS was worse in the highest quartile of ESAs responsiveness index (ERI, ESA dose divided by hemoglobin) when compared with 1st quartile (6.5 ± 4.5 versus 4.4 ± 3.4; P < 0.001). Both C-reactive protein (log CRP) (β = 0.19) and interleukin-6 (log IL-6) (β = 0.32) were strong and independent predictors of ERI using multivariate linear regression. Serum albumin (β = −0.30) and prealbumin levels (β = −0.14) were inversely associated with ERI. Each 1 SD higher MIS, higher CRP and lower albumin were associated with 86, 44 and 97% higher likelihood of having highest versus three lowest ERI quartiles in fully adjusted models [odds ratio (and 95% confidence interval) of 1.86 (1.31–2.85), 1.44 (1.08–1.92) and 1.97 (1.41–2.78)], respectively. Cubic splines confirmed the continuous and incremental nature of these associations. Conclusions Malnutrition–inflammation complex is an incremental predictor of poor responsiveness to ESAs in hemodialysis patients. Further studies are needed to assess whether modulating inflammatory or nutritional processes can improve anemia management. [ABSTRACT FROM AUTHOR]

Background The implications of chemical hyperparathyroidism on bone and mineral metabolism measures in maintenance hemodialysis (MHD) are not well known. We hypothesized that a higher serum intact parathyroid hormone (iPTH) level is associated with the higher likelihood of hyperphosphatemia, hyperphosphatasemia [high serum alkaline phosphatase (ALP) levels] and hypercalcemia. Methods Over an 8-year period (July 2001–June 2009), we identified 106 760 MHD patients with iPTH and calcium (Ca), phosphorous (P) and ALP data from a large dialysis clinic. Logistic regression models were examined to assess the association between serum iPTH increments and the likelihood of hyperphosphatemia (P ≥5.5 mg/dL), hypercalcemia (Ca ≥10.2 mg/dL) and hyperphosphatasemia (ALP ≥120 U/L). Results Patients were 61 ± 16 years old and included 45% women, 59% diabetics and 33% Blacks. Compared with an iPTH level of 100 to <200 pg/mL, patients with an iPTH level of 600–700, 700 to <800 and ≥800 pg/mL had 122% (OR: 2.22, 95% CI: 2.04–2.41), 153% (OR: 2.53, 95% CI: 2.29–2.80) and 243% (OR: 3.43, 95% CI: 3.22–3.66) higher risk of hyperphosphatemia, respectively, and had 109% (OR: 2.09, 95% CI: 1.93–2.26), 130% (OR: 2.30, 95% CI: 2.10–2.52) and 376% (OR: 4.76, 95% CI: 4.50–5.04) higher risk of hyperphosphatasemia, respectively. Compared with an iPTH level of 100 to <200 pg/mL, both the low iPTH (<100 pg/mL, OR: 2.45, 95% CI: 2.27–2.64) and the high iPTH (≥800 pg/mL: OR: 2.13, 95% CI: 1.95–2.33) levels were associated with hypercalcemia. Conclusions Higher levels of iPTH are incremental correlates of hyperphosphatemia and hyperphosphatasemia, whereas both very low and high PTH levels are linked to hypercalcemia. If these associations are causal, correction of hyperparathyroidism may have overarching implications on bone and mineral disorders in MHD patients. [ABSTRACT FROM AUTHOR]

Background Maintenance hemodialysis (MHD) patients with polycystic kidney disease (PKD) have better survival than non-PKD patients. Mineral and bone disorders (MBD) are associated with accelerated atherosclerosis and cardiovascular death in MHD patients. It is unknown whether the different MBD mortality association between MHD populations with and without PKD can explain the survival differential. Methods Survival models were examined to assess the association between different laboratory markers of MBD [such as serum phosphorous, parathyroid hormone (PTH), calcium and alkaline phosphatase] and mortality in a 6-year cohort of 60 089 non-PKD and 1501 PKD MHD patients. Results PKD and non-PKD patients were 57 ± 13 and 62 ± 15 years old and included 46 and 45% women and 14 and 32% Blacks, respectively. Whereas PKD individuals with PTH 150 to <300 pg/mL (reference) had the lowest risk for mortality, the death risk was higher in patients with PTH <150 [hazard ratio (HR): 2.16 (95% confidence interval 1.53–3.06)], 300 to <600 [HR: 1.30 (0.97–1.74)] and ≥600 pg/mL [HR: 1.46 (1.02–2.08)], respectively. Similar patterns were found in non-PKD patients. Fully adjusted death HRs of time-averaged serum phosphorous increments <3.5, 5.5 to <7.5 and ≥7.5 mg/dL (reference: 3.5 to <5.5 mg/dL) for PKD patients were 2.82 (1.50–5.29), 1.40 (1.12–1.75) and 2.25 (1.57–3.22). The associations of alkaline phosphatase and calcium with mortality were similar in PKD and non-PKD patients. Conclusion Bone–mineral disorder markers exhibit similar mortality trends between PKD and non-PKD MHD patients, although some differences are observed in particular in low PTH and phosphorus ranges. [ABSTRACT FROM PUBLISHER]

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 ≥ 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. [ABSTRACT FROM AUTHOR]

Provides information on a study which characterized whole-cell potassium currents that are under circadian control in cultured basal retinal neurons (BRN) of Bulla. Materials and methods of the study; Outward potassium current; Circadian modulation of outward currents.

Background: Focal segmental glomerulosclerosis (FSGS) in pediatric patients is typically difficult to treat and will progress to end-stage renal disease (ESRD) in about 10% of cases. Following kidney transplantation, FSGS can recur in up to 56% of renal allografts—with a near 100% recurrence in subsequent transplants. Methods: Four different pediatric centers across the USA and the UK employed a protocol using LDL-apheresis (LDL-A) and pulse solumedrol to treat recurrent FSGS after transplantation in seven patients. All the patients included in this series demonstrated immediate, or early, recurrence of FSGS, which clinically presented as nephrotic-range proteinuria within hours to days after implantation of the kidney. Results: All patients experienced reductions in urinary protein to creatinine ratios resulting in partial or complete remission. All patients demonstrated improvements in their estimated GFRs at their most recent follow-up since LDL-A discontinuation. Conclusions: This case series describes the successful treatment, across four different pediatric centers, of seven pediatric patients with recurrent post-transplant FSGS using the Liposorber® LA-15 in combination with pulse solumedrol. [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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Exposure 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. Methods: We 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. Results: Resulting studies were highly diagnostic and were pivotal in guiding patient management. The images were notable for clear delineation of multiple vascular occlusions. Conclusions: Given 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. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD), who usually display low serum 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are at high risk of infection, notably those undergoing peritoneal dialysis (PD). We hypothesized that peritoneal macrophages from PD patients are an important target for vitamin D-induced antibacterial activity. Dialysate effluent fluid was obtained from 27 non-infected PD patients. Flow cytometry indicated that PD cells were mainly monocytic (37.9±17.7% cells CD14+/CD45+). Ex vivo analyses showed that PD cells treated with 25D (100 nM, 6 hrs) or 1,25D (5 nM, 6 hrs) induced mRNA for antibacterial cathelicidin (CAMP) but conversely suppressed mRNA for hepcidin (HAMP). PD cells from patients with peritonitis (n = 3) showed higher baseline expression of CAMP (18-fold±9, p<0.05) and HAMP (64-fold±7) relative to cells from non-infected patients. In 12 non-infected PD patients, oral supplementation with a single dose of vitamin D2 (100,000 IU) increased serum levels of 25D from 18±8 to 41±15 ng/ml (p = 0.002). This had no significant effect on PD cell CD14/CD45 expression, but mRNA for HAMP was suppressed significantly (0.5-fold, p = 0.04). Adjustment for PD cell CD14/CD45 expression using a mixed linear statistical model also revealed increased expression of CAMP (mRNA in PD cells and protein in effluent) in vitamin D-supplemented patients. These data show for the first time that vitamin D supplementation in vitro and in vivo promotes innate immune responses that may enhance macrophage antibacterial responses in patients undergoing PD. This highlights a potentially important function for vitamin D in preventing infection-related complications in CKD. [ABSTRACT FROM AUTHOR]

Background: Neonates with inborn errors of metabolism (IEM) often develop hyperammonemia which, if not corrected quickly, may result in poor neurologic outcomes. As pharmacologic therapy cannot rapidly lower ammonia levels, dialysis is frequently required. Both hemodialysis (HD) and standard-dose continuous renal replacement therapy (CRRT) are effective; however, HD may be followed by post-dialytic ammonia rebound, and standard-dose CRRT may not effect a rapid enough decrease in ammonia levels. Case-Diagnosis/Treatment: We present two cases of IEM-associated neonatal hyperammonemia in which we employed a biphasic, high-dose CRRT treatment strategy, initially using dialysate flow rates of 5,000 mL/h (approximately 40,000 mL/h/1.73 m) in order to rapidly decrease ammonia levels, then decreasing the dialysate flow rates to 500 mL/h (approximately 4,000 mL/h/1.73 m) in order to prevent ammonia rebound. Conclusions: This biphasic dialytic treatment strategy for neonatal hyperammonemia effected rapid ammonia reduction without rebound and accomplished during a single dialysis run without equipment changes. [ABSTRACT FROM AUTHOR]

Calcific uremic arteriolopathy (CUA) is a rare, life-threatening disease, typically affecting patients with end-stage renal disease. It is characterized by widespread vascular calcification, endothelial fibrosis and end-organ ischemia. The mortality rate is high with infection and sepsis being the most common causes of death. Common therapies include restoration of calcium and phosphorous homeostasis, wound care and pain control. Although soft tissue calcification is a known complication in children with advanced renal disease, the incidence of CUA in pediatrics remains unknown. Additionally, current literature regarding its management in pediatric patients is lacking. We report the case of a 17-year-old African–American male patient with end-stage renal disease secondary to Wegener’s granulomatosis who developed CUA after 3 years on peritoneal dialysis. Treatment with sodium thiosulfate (STS) and hyperbaric oxygen (HBO) therapy alone was ineffective, forcing the patient to undergo bilateral below the-knee-amputation (BKA) 5 months after presentation. It was not until peritoneal dialysis had been changed to daily hemodialysis, while continuing STS and HBO therapy, that the patient demonstrated complete resolution of CUA on repeat bone scan. Based on these findings, and the extremely high mortality rate associated with this disease, CUA management requires early and aggressive intervention with multi-faceted therapy, including prompt conversion from peritoneal dialysis to hemodialysis, STS infusions and hyperbaric oxygen therapy. [ABSTRACT FROM AUTHOR]

Sevelamer hydrochloride (HCl), a calcium-free phosphate binder, is increasingly used due to concerns related to calcium exposure and the development of vascular calcifications. However, a common side effect of sevelamer HCl, metabolic acidosis, is particularly concerning in children, as it can contribute to poor growth. Sevelamer carbonate is now available and has been shown to increase serum bicarbonate in adult patients. We conducted a prospective single-center study of pediatric dialysis patients comparing serum bicarbonate before and 3 months after a switch from sevelamer HCl to sevelamer carbonate. Inclusion criteria were a minimum of 3 months of dialysis therapy and either a serum bicarbonate <20 mmol/L or the need for sodium bicarbonate supplementation. Ten hemodialysis and 14 peritoneal dialysis patients, aged 16 ± 3 years, were enrolled. Whereas serum calcium and phosphorus remained unchanged, serum bicarbonate increased from 20 (17.2–22.0) to 24.5 (20.75–26) mmol/L ( p < 0.001) after 3 months of sevelamer carbonate therapy. Sodium bicarbonate supplementation was stopped in all patients ( n = 10), reducing the mean daily sodium intake by an average of 2.3 g per patient. These results demonstrate that sevelamer carbonate is an effective phosphate binder that improves acid-base status in pediatric dialysis patients. [ABSTRACT FROM AUTHOR]

While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry. The overall prevalence of underweight, and overweight/obesity at start of CPD was 8.9% and 19.7%, respectively. Underweight was most prevalent in South and Southeast Asia (20%), Central Europe (16.7%) and Turkey (15.2%), whereas overweight and obesity were most common in the Middle East (40%) and the US (33%). BMI SDS at PD initiation was associated positively with current eGFR and gastrostomy feeding prior to PD start. Over the course of PD BMI SDS tended to increase on CPD in underweight and normal weight children, whereas it decreased in initially overweight patients. In infancy, mortality risk was amplified by obesity, whereas in older children mortality was markedly increased in association with underweight. Both underweight and overweight are prevalent in pediatric ESKD, with the prevalence varying across the globe. Late dialysis start is associated with underweight, while enteral feeding can lead to obesity. Nutritional abnormalities tend to attenuate with time on dialysis. Mortality risk appears increased with obesity in infants and with underweight in older children. [ABSTRACT FROM AUTHOR]