Chronic Kidney Disease In Children Research Articles

Association Between Salivary Cytokines, Chemokines and Growth Factors and Salivary Gland Function in Children with Chronic Kidney Disease.

Chronic kidney disease (CKD) is a systemic inflammatory disease that leads to multiple organ complications not only in the kidneys and the cardiovascular system, but also in the oral cavity. CKD children experience reduced saliva secretion (hyposalivation), which leads to increased incidence of dental caries and significant impairment of patients' quality of life. However, the causes of salivary gland dysfunction in children with CKD are unknown. The present study is the first to evaluate the inflammatory and anti-inflammatory profile in the saliva of children with CKD at different stages of renal failure with normal and reduced salivary gland function. Thirty children with CKD (age 9-16) and thirty age- and gender-matched healthy children were classified for the study. Salivary inflammatory and anti-inflammatory profile were assayed using the multiplex ELISA assay. We demonstrated statistically significant changes in salivary pro-inflammatory (↑TNF-α, ↓IL-7), anti-inflammatory (↑IL-10), Th1 (↑INF-γ, ↑IL-15), Th2 (↑IL-4, ↑IL-5, ↑IL-6, ↑IL-9) and Th17 (IL-17) cytokines as well as chemokines (↑MCP-1/CCL-2, ↑MIP-1α/CCL3, ↓MIP-1β/CCL4, ↓EOTAXIN/CCL11) and growth factors (↑G-CSF, ↑FGF) in unstimulated saliva of children with CKD compared to the controls. Although the evaluation of the salivary inflammatory profile does not indicate a particular dominance of any of the branches of the immune system, we observed a statistically significant increase in the concentration of all Th2 cytokines assayed. The multivariate regression analysis showed that the content of salivary cytokines, chemokines and growth factors depends on the secretory function of the salivary glands, ie, salivary flow, total protein concentration and amylase activity in the saliva. Salivary MIP-1α/CCL3 was the most effective to differentiate children with CKD and hyposalivation from patients with normal saliva secretion. Inflammation is involved in salivary gland dysfunction in children with CKD, although further studies on in vitro and in vivo models are necessary to confirm this hypothesis.

Abstract P212: Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children

Introduction: There is inconsistent evidence on the efficacy of a low-protein diet for patients with chronic kidney disease (CKD) and there is a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein among children with CKD and to assess whether protein-related metabolites are associated with CKD progression. Methods: We conducted non-targeted metabolomics using plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, non-drug metabolites and dietary intake of dairy, nuts and beans, red and processed meat, fish, chicken, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards regression models assessed the prospective association between protein-related metabolites and CKD progression defined as kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. We used a false discovery rate <0.05 as the statistical significance threshold to account for multiple comparisons. Results: Fifty-seven unique metabolites were significantly associated with dietary protein intake (dairy: n=21; nuts and beans: n=13; red and processed meat: n=20; fish: n=2; chicken: n=3; eggs: n=0). Among them, ten metabolites were significantly associated with CKD progression (TABLE) , including one amino acid, one cofactor and vitamin, four lipids, two nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-GPE (P-16:0/18:1) was positively associated with dietary intake of red and processed meat and CKD progression, and 3-ureidopropionate was inversely associated with dietary intake of red and processed meat and CKD progression. Conclusion: Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

Egyptian pediatric clinical practice adapted guidelines: evidence-based [2] steroid-resistant nephrotic syndrome (SRNS) 2022

BackgroundNephrotic syndrome is one of the most common chronic kidney diseases in children. Steroid sensitive type (SSNS) constitutes about 85–90%, whereas steroid-resistant type (SRNS) only 15–20% (Mickinney et al. Pediatr Nephrol 16:1040-1044, 2001). While MCD is the most common histopathology in SS type, children with SRNS have MCD, mesangial proliferative glomerulonephritis, or focal and segmental glomerulosclerosis (FSGS) (International Study Kidney Disease in children, Kidney Int 20;765-771, 1981). SRNS is defined as those who do not show remission after 6 weeks and standard dose of oral steroids ± 3 IV MPD doses (Trautmann et al. Pediatr Nephrol 35:1529-1561, 2020).ObjectivesThese national adapted guidelines aim to frame evidence-based recommendations adopted or adapted from the IPNA 2020, KDIGO 2021, and Japanese 2014 de novo guidelines for diagnosis and management of nephrotic children to be presented in two manuscripts: (1) steroid sensitive (SSNS) and (2) steroid-resistant nephrotic syndrome (SRNS).MethodologyFormulation of key questions was followed with a review of literature guided by our appraised guidelines using AGREE plus appraisal tool. Virtual monthly meetings all through the year 2021 were activated for reviewing and validation of final adaptation evidence-based draft, considering all comments of external reviewers including KDIGO assigned reviewer.DiscussionRationale behind the selection of adopted statements and tailoring of others to suit our local facilities, expertise, and our local disease profile was discussed in the text with reasons.ConclusionThe provided guidelines aim to optimize patient care and outcome and suggest research areas lacking validated research recommendations.

Egyptian evidence -based pediatric clinical practice adapted guidelines for management of [1] steroid sensitive nephrotic syndrome (EPG/SSNS 2022)

BackgroundNephrotic syndrome is one of the most common chronic kidney diseases in children. Steroid sensitive type constitutes about 90% and steroid resistant 10% of total cases. ObjectivesThese national adapted guidelines aim to frame evidence-based recommendations adopted or adapted from IPNA 2020, KDIGO 2021, and Japanese 2014 for diagnosis, evaluation, management and follow-up of nephrotic children for Steroid sensitive nephrotic syndrome (SSNS) as paper one to be followed with SRNS as paper two.MethodologyFormulation of key questions was followed with review of literature, guided by our retrieved and appraised guidelines using Agree plus appraisal tool. After virtual monthly meetings through the year 2021, the final draft was validated considering the comments of external local reviewers and KDIGO-assigned reviewers. DiscussionRationale behind the selection of adopted statements and tailoring of others to suit our local facilities’ expertise and disease profile was discussed in the text with reasons.ConclusionThe provided guidelines aim to optimize patient care and outcome and suggest research areas lacking validated research recommendations.

Bioelectrical Impedance Analysis for Nutritional Assessment in Children with Chronic Kidney Disease

Background: Malnutrition and growth failure are major problems among children with chronic kidney disease (CKD). No single metric can describe their nutritional status; therefore, a series of indices and methods are required for evaluation.
 Aim of the Work: Evaluation of the nutritional status of children with CKD using dietetic history, anthropometric measurements, biochemical parameters and BIA.
 Methods: This case-control study was conducted on forty CKD children (stages 3-5) from those attending Pediatric Department, Tanta University Hospitals between March 2021 and February 2022 in comparison to forty healthy control children. All were subjected to: dietetic history, anthropometric measurements including (weight, height, body mass index, mid-arm circumference, skin fold thickness), BIA using TANITA Body Composition Analyzer MC-980 MA-N plus III device and laboratory investigations: (CBC, urea, creatinine, ABG, sodium, potassium, phosphorus, calcium, alkaline phosphatase, parathormone hormone, serum proteins, albumin and 24hrs urinary proteins).
 Results: CKD children had significantly lower caloric intake and other nutrient consumption including protein, carbohydrate and fat intake (p < 0.05), significantly lower anthropometric measurements including weight, height, body mass index, skinfold thickness and mid-arm circumference than controls (p < 0.05) and significantly lower in BIA measurements including fat mass (FM), fat free mass (FFM), muscle mass (MM), total body water (TBW) and bone mass (BM) than controls. There was significant positive correlation between caloric intake and protein intake with FFM, MM, SMM, BM, TBW and BMR, also there was significant positive correlation between serum albumin and FFM, MM, SMM, BM and TBW in CKD patients.
 Conclusions: CKD children had low caloric and protein intake, low body composition parameters, so good nutritional assessment and improvement of their nutritional status is very important. BIA could be used with dietary assessment and anthropometric measurements to achieve more accurate nutritional evaluation in CKD children.

A rare presentation of end stage kidney disease in a 15-year-old girl: A case report

Introduction: Chronic kidney disease (CKD) among children is on the rise, both locally and globally. The burden of managing CKD in children from resource-poor centers and the developing nations as a whole is quite challenging. Pediatric CKD has remained a death sentence in many poor nations of the world, including Nigeria. Chronic kidney disease is asymptomatic in its earliest stages, although urinalysis findings or blood pressure may be abnormal. As CKD progresses to more advanced stages, signs and symptoms greatly increase, making the diagnosis of CKD more obvious. Case Report: We hereby report a rare presentation of only headache, sudden blindness, hypertension, and retinal detachment as the only pointer to end stage kidney disease (ESKD) in a 15-year-old girl. Conclusion: There is need for nephro-prevention in children, and a higher index of suspicion for CKD, with the intention of reducing or halting disease progression at earlier stages of the disease.

CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood

The global prevalence of chronic kidney disease (CKD) is increasing rapidly, due to increasing environmental stressors through the life cycle. Congenital anomalies of kidney and urinary tract (CAKUT) account for most CKD in children, with a spectrum that can lead to kidney failure from early postnatal to late adult life. A stressed fetal environment can impair nephrogenesis, now recognized as a significant risk factor for the development of adult CKD. Congenital urinary tract obstruction is the leading cause of CKD due to CAKUT and can itself impair nephrogenesis as well as contribute to progressive nephron injury. Early diagnosis by ultrasonography in fetal life by an obstetrician/perinatologist can provide important information for guiding prognosis and future management. This review focuses on the critical role played by the pediatrician in providing timely evaluation and management of the patient from the moment of birth to the transfer to adult care. In addition to genetic factors, vulnerability of the kidney to CKD is a consequence of evolved modulation of nephron number in response to maternal signaling as well as to susceptibility of the nephron to hypoxic and oxidative injury. Future advances in the management of CAKUT will depend on improved biomarkers and imaging techniques.

ACTUALITIES IN THE MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM DUE TO CHRONIC KIDNEY DISEASE IN CHILDREN.

Pediatric chronic kidney disease (CKD) has a substantial global impact because is associated with notable morbidity. Secondary hyperparathyroidism (SPHT) frequently emerges as a complication in the early stages of renal insufficiency, it is an adaptive response to uphold mineral balance. It is a component of the chronic kidney disease-mineral and bone disorder (CKD-MBD). The development of SHPT in CKD involves multiple factors and it is important to understand them in order to properly manage it, starting with early diagnosis and continuing with proper treatment. In children with CKD and SHPT, the difficulty in case management is due to non-adherence to proper diet which makes it difficult for the pediatric nephrologist to manage the case. In this review we want to focus on new data regarding this CKD complication.

Nutritional Assessment and Support in Children with Chronic Kidney Disease: The Benefits of Working with a Registered Dietitian.

An unbalanced dietary pattern, characterized by high animal protein content: may worsen metabolic control, accelerate renal deterioration and consequently aggravate the stage of the chronic kidney disease (CKD) in pediatric patients with this condition. to assess the effect of a registered dietitian (RD) intervention on the CKD children's eating habits. Anthropometric and dietetic parameters, obtained at baseline and 12 months after implementing healthy eating and nutrition education sessions, were compared in 16 patients (50% girls) of 8.1 (1-15) years. On each occasion, anthropometry, 3-day food records and a food consumption frequency questionnaire were carried out. The corresponding relative intake of macro- and micronutrients was contrasted with the current advice by the European Food Safety Authority (EFSA) and with consumption data obtained using the Spanish dietary guidelines. Student's paired t-test, Wilcoxon test and Mc Nemar test were used. At Baseline 6% were overweight, 69% were of normal weight and 25% were underweight. Their diets were imbalanced in macronutrient composition. Following nutritional education and dietary intervention 63%, 75% and 56% met the Dietary Reference Values requirements for fats, carbohydrates and fiber, respectively, but not significantly. CKD children decreased protein intake (p < 0.001), increased dietary fiber intake at the expense of plant-based foods consumption (p < 0.001) and a corresponding reduction in meat, dairy and processed food intake was noticed. There were no changes in the medical treatment followed or in the progression of the stages. RD-led nutrition intervention focused on good dieting is a compelling helpful therapeutic tool to improve diet quality in pediatric CKD patients.

Identification of Novel Genetic Risk Factors for Focal Segmental Glomerulosclerosis in Children: Results From the Chronic Kidney Disease in Children (CKiD) Cohort

Focal segmental glomerulosclerosis (FSGS) is a major cause of pediatric nephrotic syndrome, and African Americans exhibit an increased risk for developing FSGS compared with other populations. Predisposing genetic factors have previously been described in adults. Here we performed genomic screening of primary FSGS in a pediatric African American population. Prospective cohort with case-control genetic association study design. 140 African American children with chronic kidney disease from the Chronic Kidney Disease in Children (CKiD) cohort, including 32 cases with FSGS. Over 680,000 common single-nucleotide polymorphisms (SNPs) were tested for association. We also ran a pathway enrichment analysis and a human leucocyte antigen (HLA)-focused association study. Primary biopsy-proven pediatric FSGS. Multivariate logistic regression models. The genome-wide association study revealed 169 SNPs from 14 independent loci significantly associated with FSGS (false discovery rate [FDR]<5%). We observed notable signals for genetic variants within the APOL1 (P=8.6×10-7; OR, 25.8 [95% CI, 7.1-94.0]), ALMS1 (P=1.3×10-7; 13.0% in FSGS cases vs 0% in controls), and FGFR4 (P=4.3×10-6; OR, 24.8 [95% CI, 6.3-97.7]) genes, all of which had previously been associated with adult FSGS, kidney function, or chronic kidney disease. We also highlighted novel, functionally relevant genes, including GRB2 (which encodes a slit diaphragm protein promoting podocyte structure through actin polymerization) and ITGB1 (which is linked to renal injuries). Our results suggest a major role for immune responses and antigen presentation in pediatric FSGS through (1) associations with SNPs in PTPRJ (or CD148, P=3.5×10-7), which plays a role in T-cell receptor signaling, (2) HLA-DRB1∗11:01 association (P=6.1×10-3; OR, 4.5 [95% CI, 1.5-13.0]), and (3) signaling pathway enrichment (P=1.3×10-6). Sample size and no independent replication cohort with genomic data readily available. Our genetic study has identified functionally relevant risk factors and the importance of immune regulation for pediatric primary FSGS, which contributes to a better description of its molecular pathophysiological mechanisms. We assessed the genetic risk factors for primary focal segmental glomerulosclerosis (FSGS) by simultaneously testing over 680,000 genetic markers spread across the genome in 140 children, including 32 with FSGS lesions. Fourteen independent genetic regions were significantly associated with pediatric FSGS, including APOL1 and ALMS1-NAT8, which were previously found to be associated with FSGS and chronic kidney diseases in adults. Novel genes with relevant biological functions were also highlighted, such as GRB2 and FGFR4, which play a role in the kidney filtration barrier and in kidney cell differentiation, respectively. Finally, we revealed the importance of immune regulation in pediatric FSGS through associations involving cell surface proteins presenting antigens to the immune system and interacting with T-cell receptors.

Risk Factors for Progressive Chronic Kidney Disease in Children with Idiopathic Nephrotic Syndrome at Dr. Mohammad Hoesin General Hospital Palembang

Nephrotic syndrome (NS) is a kidney disease that is often found in children. NS can cause infectious and non-infectious complications, such as upper respiratory tract infections, urinary tract infections, edema, acute kidney injury (AKI), and hypertension. This study aimed to determine the risk factors of age, gender, nutritional status, hypertension, hematuria, AKI, hyperfiltration, and steroid sensitivity to the progression of chronic kidney disease (CKD) in children with the initial idiopathic NS in the pediatric ward of Dr. Mohammad Hoesin General Hospital Palembang. This study was an analytic observational study with a cross-sectional design. A total of 72 secondary data of research subjects were included in this study. Risk factor analysis was carried out with the help of SPSS version 24 software in univariate, bivariate, and multivariate ways. The most common risk factor for children with the initial idiopathic NS is age ≥10 years, males and females gender obtained the same number, and the nutritional status of obesity, hematuria, AKI, and hyperfiltration have quite low rates. However, hypertension and SRNS have high rates in children with initial idiopathic NS. In conclusion, hypertension and hyperfiltration are risk factors that play a role in initiating the progression of idiopathic NS to CKD in the pediatric ward of Dr. Mohammad Hoesin General Hospital, Palembang.

Comparing Estimated and Measured Glomerular Filtration Rate in Children with Posterior Urethral Valve.

Posterior urethral valve (PUV) is obstructive uropathy that may lead to chronic kidney disease (CKD) and end-stage renal disease (ESRD) in children. Glomerular filtration rate (GFR) measurement remains the gold standard for renal function measurement. However, due to its less availability and cumbersome, it is not commonly used, and GFR is estimated utilizing various endogenous filtration markers. This study includes pediatric patients with PUV. We aimed to compare the measured GFR (mGFR) with various creatinine-based estimated GFR methods (eGFR). A single-center retrospective study included 62 treated cases of PUV, postvalve fulguration. The mGFR measured by 99mTc-diethylenetriaminepentaacetate in vitro method and compared with eight eGFR (Schwartz, Cockcroft-Gault [CG], Counahan-Barratt [CB], CKD Epidemiology Collaboration [CKD-EPI], full-age spectrum [FAS] age, FAS height (FAS Ht), Schwartz-Lyon [SL], and Ht independent). Patients were subdivided into different CKD grades and compared with various eGFR. PUV is a common cause of CKD in children and needs special consideration as there is growth retardation associated with it. It decreases creatinine production and thus fallacies in eGFR measurement. There is a requisite to identify and closely monitor the subset of patients with baseline decreased renal function and therefore at risk of developing ESRD. A total of 62 patients were included. Mean age and serum creatinine levels were 8.02 ± 5.53 years and 1.15 ± 0.95 mg/dl (range: 0.4-4.5), respectively. The mean mGFR was 61.6 ± 31.80 mL/min/1.73 m2 and a positive variable correlation was 0.46-0.77 between mGFR and eGFR. Based on mGFR, there were 14 (22.6%), 21 (33.8%), 13 (20.9%), 9 (14.5%), and 5 (8.1%) patients in Grades I-V, respectively. The correct classification of the CKD grades was noted in 25 (40.3%), 16 (25.8%), 32 (51.6%), 16 (25.8%), 25 (40.3%), 27 (43.5%), 26 (41.9%), and 28 (45.2%) patients by Schwartz, CG, CB, CKD-EPI, FAS age, FAS Ht, SL, and Ht-independent equation. The eGFR overestimates GFR at the lower level and underestimates at higher levels. Our results confirm the considerable limitations of various creatinine-based clearance methods for estimating actual GFR. The creatinine clearance-based eGFR should not replace the measurement of the GFR. An initial measure of the mGFR followed by serial follow-up with the eGFR equation may be done. The most accurate eGFR equations are CB for Grade II, SL or Ht independent for Grade III, FAS age for Grade IV, and SL for Grade V CKD.

Структура кардиоваскулярных нарушений у детей с хронической болезнью почек

Objective. To study the structure of cardiovascular pathology in children with chronic kidney disease (CKD). Patients and methods. 74 children were examined, including 40 patients on dialysis and 34 patients at the predialysis stage of CKD. The following parameters were determined: the thickness of the interventricular septum and the posterior wall of the left ventricle (LV), the final systolic and final diastolic LV size, shock volume, ejection fraction. The myocardial mass index (LVMI) and the relative wall thickness (RWT) of the LV were calculated according to the following formulas. Results. According to echocardiography data in children receiving dialysis, LV myocardial hypertrophy was observed in the majority of children – 17 (42.5%, p &lt; 0.001), of which in 35.3% of cases (6 children) concentric remodeling was detected (RWT ≥0.45, LVH within 90 g/m2), in 41.2% of cases (in 7 patients), concentric hypertrophy was determined (RWT ≥0.45, LVMI 111.7 ± 11.4 g/m2), eccentric hypertrophy was detected in 23.5% of patients (in 4 – RWT ≤0.45, IMLJ 115.6 ± 11.9 g/m2); systolic dysfunction was found in 10 (25%) children with stage 5d CKD, in 8 (20%) – diastolic dysfunction, in 5 (12.5%) – the valvular damage. In 19 (55.9%) children with the predialysis stage, there is a normal LV geometry (RWT &lt;45 with normal LV), in 15 (44.1%) – concentric remodeling (RWT &gt;45 with normal LVMI). Conclusion. CKD in children, as in adults, is associated with the highest risk of accelerated development of cardiovascular pathology. Cardiovascular pathology in CKD is manifested mainly by LV myocardial hypertrophy. LV hypertrophy, being an important risk factor for arrhythmias and heart failure, is especially characteristic of patients with dialysis for,m of CKD. Key words: cardiovascular disorders, chronic kidney disease

Therapy with erythropoietin-alpha and erythropoietin-beta for anemia of chronic kidney disease in children on maintenance hemodialysis

Therapy with erythropoietin-alpha and erythropoietin-beta for anemia of chronic kidney disease in children on maintenance hemodialysis

Neuroimmunological renal function for zinc(Ⅱ) induced CKD prevention and modulatory progression

Zinc (Ⅱ) supplementation (30 mg/day) should become likely therapeutic chronic kidney disease (CKD) prevention implications with immense importance of CKD-associated immunological and neurological complications of central nervous system (CNS) disorder and peripheral nervous system (PNS) condition. Zinc induced neuro immunological inhibitive CKD progression with Stage 2～3A, 3B, zinc supplementation may be beneficial for nutritional status in CKD children and adolescents, and zinc could reduce urinary protein excretion composed of albumin and/or minimize proteinuria excretion in proteinuric CKD. In CKD 4～5 stage, risk of cardiovascular disease (CVD) become higher that zinc supplementation of 25 mg/day in zinc homeostasis has a beneficial effect for CVD in vascular dysfunction, in which zinc induced CKD Stage 5 (eGFR < 15) is involved that zinc is actively bound to several proteins that the decrease of circulating zinc levels in CKD is becoming zinc-deficiency with advanced stage CKD and ESRD in CKD. Zinc 15 mg/day and Selenium 50–70 μg/day that are recommended may be thought to prevent ESRD stage. Zinc induced NAD (P)H oxidase (Nox) activation occurring ROS generation in CKD cell involves assembly that ROS include the superoxide anion (O2•–), hydrogen peroxide (H2O2), and hydroxyl radicals (OH•) in the kidney. Zinc(Ⅱ) ions-binding protein molecular mechanism is involved that Zn2+ ions induced binding ligands of such as albumin, a-macroglobulin and transferrin in several proteins had been found on the binding specificity by Zn2+ ions-centered tetrahedral geometric coordination, in which causing zinc-activated serine, histidine and aspartate hydrogen residues enhance renal function activity and resulting inhibition of CKD progression proceeds.

Innovative Ultrasound Diagnostic Technologies for Chronic Kidney Disease in Children

The most pressing problems facing modern pediatrics and nephrology is chronic kidney disease (CKD) which is associated with an orderly onset of disorders in patients in childhood, a constant increase in the incidence of chronic progressive kidney disease and the occurrence of chronic renal failure (CRF). Despite recent advances in nephrology, reducing the risk of problems associated with delayed CRF and reduced kidney function remains a challenge in the early detection and prevention of kidney disease of various etiologies.

Blood Pressure Classification Status in Children With CKD Following Adoption of the 2017 American Academy of Pediatrics Guideline

Accurate detection of hypertension is crucial for clinical management of pediatric chronic kidney disease (CKD). The 2017 American Academy of Pediatrics (AAP) clinical practice guideline for childhood hypertension included new normative blood pressure (BP) values and revised definitions of BP categories. In this study, we examined the effect of applying the AAP guideline's normative data and definitions to the Chronic Kidney Disease in Children (CKiD) cohort compared with use of normative data and definitions from the 2004 Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Observational cohort study. Children and adolescents in the CKiD cohort. Clinic BP measurements. BP percentiles and hypertension stages calculated using the 2017 AAP guideline and the Fourth Report from2004. Agreement analysis compared the estimated percentile and prevalence of high BP based on the 2017 guideline and 2004 report to clinic and combined ambulatory BP readings. The proportion of children classified as having normal clinic BP was similar using the 2017 and 2004 systems, but the use of the 2017 normative data classified more participants as having stages 1-2 hypertension (22% vs 11%), with marginal reproducibility (κ=0.569 [95% CI, 0.538-0.599]). Those identified as having stage 2 hypertension by the 2017 guideline had higher levels of proteinuria compared with those identified using the 2004 report. Comparing use of the 2017 guideline and the 2004 report in terms of ambulatory BP monitoring categories, there were substantially more participants with white coat (3.5% vs 1.5%) and ambulatory (15.5% vs 7.9%) hypertension, but the proportion with masked hypertension was lower (40.2% vs 47.8%, respectively), and the percentage of participants who were normotensive was similar (40.9% vs 42.9%, respectively). Overall, there was good reproducibility (κ=0.799 [95% CI, 0.778-0.819]) of classification by ambulatory BP monitoring. Relationship with long-term progression and target organ damage was not assessed. A greater percentage of children with CKD were identified as having hypertension based on both clinic and ambulatory BP when using the 2017 AAP guideline versus the Fourth Report from 2004, and the 2017 guideline better discriminated those with higher levels of proteinuria. The substantial differences in the classification of hypertension when using the 2017 guideline should inform clinical care.

Longitudinal Relationship Between Anemia and Statural Growth Impairment in Children and Adolescents With Nonglomerular CKD: Findings From the Chronic Kidney Disease in Children (CKiD) Study

Anemia and statural growth impairment are both prevalent in children with nonglomerular chronic kidney disease (CKD) and are associated with poor quality of life and increased morbidity and mortality. However, to date no longitudinal studies have demonstrated a relationship between anemia and statural growth in this population. The CKD in Children (CKiD) study is a multicenter prospective cohort study with over 15 years of follow-up observation. CKiD participants younger than 22 years with nonglomerular CKD who had not reached final adult height. Age-, sex-, and race-specific hemoglobin z score. Age- and sex-specific height z score. The relationship between hemoglobin and height was quantified using (1) multivariable repeated measures paired person-visit analysis, and (2) multivariable repeated measures linear mixed model analysis. Both models were adjusted for age, sex, body mass index, estimated glomerular filtration rate, acidosis, and medication use. Overall, 67% of the 510 participants studied had declining hemoglobin z score trajectories over the follow-up period, which included 1,763 person-visits. Compared with average hemoglobin z scores of≥0, average hemoglobin z scores of less than -1.0 were independently associated with significant growth impairment at the subsequent study visit, with height z score decline ranging from 0.24 to 0.35. Importantly, in 50% of cases hemoglobin z scores ofless than -1.0 corresponded to hemoglobin values higher than those used as cutoffs defining anemia in the KDIGO clinical practice guideline for anemia in CKD. When stratified by age, the magnitude of the association peaked in participants aged 9 years. In line with paired-visit analyses, our mixed model analysis demonstrated that in participants with baseline hemoglobin z scoreless than -1.0, a hemoglobin z score decline over the follow-up period was associated with a statistically significant concurrent decrease in height z score. Limited ability to infer causality. Hemoglobin decline is associated with growth impairment over time in children with mild to moderate nonglomerular CKD, even before hemoglobin levels reach the cutoffs that are currently used to define anemia in this population.

Estimation of glomerular filtration rate in a pediatric population using non-contrast kidney phase contrast magnetic resonance imaging.

Glomerular filtration rate (GFR) is a key measure of kidney function but often inaccurately ascertained by serum creatinine and cystatin C in pediatrics. In this pilot trial, we evaluated the relationship between GFR calculated by using phase-contrast MRI (PC-MRI) biomarkers and GFR by 125I-iothalamate clearance in youth undergoing bone marrow transplantation (BMT). A total of twenty-one pediatric BMT candidates (8-21years of age) were recruited for a research kidney PC-MRI. After completion of 125I-iothalamate clearance, same-day PC-MRI measurements were completed of the kidney circulation without a gadolinium-based contrast agent. MRI included a non-contrast balanced-SSFP-triggered angiography to position ECG-gated breath-held 2D PC-MRI flow measurements (1.2 × 1.2 × 6 mm3). A multivariate model of MRI biomarkers estimating GFR (GFR-MRI) was selected using the elastic net approach. The GFR-MRI variables selected by elastic net included average heart rate during imaging (bpm), peak aorta flow below the kidney artery take-offs (ml/s), average kidney artery blood flow, average peak kidney vein blood flow, and average kidney vein blood flow (ml/s). The GFR-MRI model demonstrated strong agreement with GFR by 125I-iothalamate (R2 = 0.65), which was stronger than what was observed with eGFR by the full age spectrum and Chronic Kidney Disease in Children under 25 (CKiD U25) approaches. In this pilot study, noninvasive GFR-MRI showed strong agreement with gold standard GFR in youth scheduled for BMT. Further work is needed to evaluate whether non-contrast GFR-MRI holds promise to become a superior alternative to eGFR and GFR by clearance techniques. A higher resolution version of the Graphical abstract is available as Supplementary information.

Thrombosis in Chronic Kidney Disease in Children.

Venous thromboembolism (VTE) in children is a rare condition. An increased incidence has been observed in the last few years due to several factors, such as increased survival in chronic conditions, especially chronic kidney disease (CKD), use of catheters, and increased sensitivity of diagnostic tools. VTE includes deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE in children is associated with a two to six times higher mortality risk and a 5-10% prevalence of post-thrombotic syndrome. Overall, 5% of VTE episodes in children are associated with chronic kidney disease. The etiology of VTE in chronic kidney disease covers a wide range of pathologies. Various types of thrombotic complications may occur during long-term use of a chronic dialysis catheter. VTE occurs in 3% of children with nephrotic syndrome (NS). The risks for VTE and arterial thromboembolism (ATE) were particularly high in the first 6 months after the onset of NS. Other causes of VTE are graft rejection due to thrombosis of vascular anastomoses after kidney transplantation (3%) and autoimmune diseases (lupus nephritis, antiphospholipid syndrome). In this state-of-the-art overview, we have reviewed the physiologic and pathologic mechanisms underlying pediatric thrombosis and updated current diagnostic and treatment options, emphasizing personal experience as well.