Kidney Disease In Children Research Articles

Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.

The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine. The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6months to 16years with estimated glomerular filtration rate (eGFR) 30-89ml/min/1.73 m2. Data from the 2-year study visit were used for this analysis. Toxin quantification (Metabolon Inc., Durham, NC) was performed with ultra-high performance liquid chromatography/tandem mass spectrometry. Executive function and echocardiograms were assessed. Regression analysis examined the association of toxin levels with eGFR, CKD etiology, and neurocognitive and cardiac assessments (adjusted for age, sex, and urine protein:creatinine [UPCR]). There were 150 CKiD participants included in this study. All toxins levels were significantly inversely correlated with eGFR (Spearman's rho - 0.45 to - 0.69). Children with non-glomerular CKD had significantly higher levels of 3-indoxylsulfate, phenylacetylglutamine, and p-cresol glucuronide. The toxin levels did not associate with neurocognitive outcomes. P-cresol glucuronide and phenylacetylglutamine negatively associated with left ventricular mass index z score, but did not associate with left ventricular hypertrophy. Children with CKD have high levels of circulating gut microbiome-derived toxins. The levels of these toxins are strongly correlated with eGFR. There appear to be differences in toxin level based on glomerular versus non-glomerular etiology, even when accounting for the differences in eGFR between these two subgroups. In this sample, we did not detect any associations between these toxin levels and neurocognitive or cardiac outcomes.

Comparison of three different cystatin C measurement procedures in a pediatric chronic kidney disease cohort: Calibration for longitudinal measurements and implications for clinical estimation of GFR.

Serum cystatin C (CysC) is used to estimate glomerular filtration rate (eGFR), including in the Chronic Kidney Disease in Children (CKiD) Under 25 years (U25eGFR) equations. Several CysC measurement procedures available from diagnostic vendors include reference material for calibration, but the extent of heterogeneity across manufacturers is unclear. Since heterogeneity may have clinical and research implications for eGFR, we evaluated three CysC procedures in samples from the CKiD study representing a wide spectrum of kidney function. The three CysC measurement procedures evaluated were: Siemens BN II N Latex CystatinC Assay; Gentian CystatinC Immunoassay; and Roche Tina-quant CystatinC Gen.2. Bland-Altman quantified agreement with Siemens as reference because that method was used for longitudinal CKiD samples from 2003 to 2023. We present derivation of the interquartile range (IQR) of U25eGFR as a measure of precision and describe differences outside this range. From 53 samples from 44 participants, Gentian measurements were 7 % higher than Siemens (95 %CI: +5.6 %,+8.5 %), while Roche measurements were 4.8 % lower on average (95 %CI: -6.2 %,-3.3 %). Both had very high correlation: 0.9926 and 0.9906, respectively. There was strong agreement across procedures, but a simple correction factor of 7 % reduction applied to Gentian yielded unbiased estimates (+0.03 %, 95 %CI: -1.3 %,+1.4 %) and strong performance in Deming regression. For precision, 98 % of U25eGFR values based on Gentian and Roche CysC were each within the IQR of the Siemens-based estimates. Despite reference material calibration, heterogeneity across CysC measurement procedures was observed. Procedure variability was within the limits of U25eGFR estimates indicating that practically, all procedures are appropriate for clinical use. Clinicians may consider calculating IQR of U25eGFR estimates for pediatric chronic kidney disease management.

Diagnostic Test Characteristics of Ultrasound-Based Hydronephrosis for Chronic Kidney Disease in Children and Adolescents With Myelomeningocele: Results From the UMPIRE and NSBPR Cohort Studies.

Renal ultrasounds are performed in patients with myelomeningocele to screen for markers of kidney health, including hydronephrosis. We evaluated the diagnostic accuracy of hydronephrosis to screen for low kidney function defined by estimated glomerular filtration rate (eGFR). We performed a retrospective cross-sectional study using data from 2 cohorts of children and youth with myelomeningocele. The first cohort is the Urological Management to Preserve Initial Renal Function Protocol for Young Children With Spina Bifida (UMPIRE; 2016-2022) and the second from the National Spina Bifida Patient Registry (NSBPR; 2009-2021). We identified patients aged 1 to 18 years with available eGFR data within 6 months of an ultrasound. We excluded NSBPR patients younger than 6 years to address potential duplication across cohorts. The primary outcome was eGFR < 90 mL/min/1.73 m2, calculated using the bedside Schwartz formula. Hydronephrosis was dichotomized into any/none. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of any hydronephrosis using eGFR as the reference standard. In UMPIRE, 221 patients were included with median age 2.4 years (IQR, 1.9-3.8) and 24% having eGFR < 90. Any hydronephrosis vs none conferred a sensitivity/specificity/PPV/NPV of 25%/75%/24%/77%, respectively. In NSBPR, 2269 patients were included with median age 13 years (IQR, 9.6-16.3) and 17% having eGFR < 90. Any hydronephrosis vs none conferred a sensitivity/specificity/PPV/NPV of 24%/87%/26%/85%, respectively. In 2 cohorts of children and youth with myelomeningocele, hydronephrosis conferred a sensitivity of ∼25% for a creatinine-based eGFR < 90 mL/min/1.73 m2. This low sensitivity suggests that hydronephrosis alone is a poor screening marker of kidney health.

“Chronic Kidney Disease In Children Of A Paediatric Critical Care Nephrology &amp; Dialysis Department: A Study In Bangladesh Shishu (Children) Hospital &amp; Institute, Bangladesh”

Introduction: Chronic Kidney Disease (CKD) for children is a major problem of public health both in poor and developed countries. This study aimed to investigate the diagnosis and the management options of CRF for children. Patients and methods: This study retrospectively evaluated patients who had chronic kidney disease (CKD) in the Paediatric Critical Care &amp; Nephrology Department in Dhaka Shishu Children Hospital, Dhaka, Bangladesh between July 2017 and December 2017. Results: Over 6 month’s period, we diagnosed and managed 41 children with CRF. The estimated incidence of CRF is 4.7 new cases per million-child population per year. Parental consanguinity was found in 16 patients (39%). Family history with kidney disease was noted in 6 cases (14.6%). Malformations of the urinary tract were observed in 24 patients (58.5%). Other causes are divided into hereditary kidney disease in 8 patients (19.5%) predominated by primary hyperoxaluria, in vascular nephropathy who were objectified in 5 patients (12%) whereas glomerulopathy were represented in 3 cases (7.5%). No etiology was found in 1 patient. Over the 6 month’s 22 patients (54%) had renal replacement therapy (RRT). Peritoneal dialysis (PD) was practiced in over then 90% of patients. A passage from peritoneal dialysis to hemodialysis was done in 8 patients. Only four patients had a kidney transplant. The rate of overall mortality in our series was 40% with median of follow-up in 54 months. Conclusion: In Tunisia and in all Low source country children with CRF must be treated by pediatric nephrologists and the pediatric renal transplantation must be developed.

Assessment of renal function in long-term surviving children after hematopoietic cell transplantation

Background Hematopoietic stem cell transplantation (HSCT) is the standard therapy for many disorders, however long-term complications post-HSCT in pediatrics remain a significant concern, where a pre-existent subclinical kidney damage, the use of nephrotoxic medications, or consequences of primary disease carry the hazard of acute kidney injury (AKI) and chronic kidney disease (CKD), which could be devastating complications, therefore identification of risk factors, prompt diagnosis, and treatment of CKD is vital for secure HSCT. So, we aimed to assess the kidney function to detect the development of CKD in our pediatric patient, using different formulas to measure the estimated glomerular filtration rate (eGFR). Patients and methods A prospective cross-sectional study was conducted at the Bone Marrow Transplantation Unit, Faculty of Medicine, Ain Shams University, Cairo, Egypt, where we included all available HSCT long-term survivors, who underwent HSCT during the period between 2011 and 2018. A detailed medical history and complications were collected from patient’s medical records, while clinical examination with measurement of serum creatinine, and Cystatin C (CysC) were done to determine eGFR, and hence CKD, using different methods; bedside Schwartz and Cockcroft Gault formulas (according to the age), serum CysC, and Chronic Kidney Disease in Children (CKiD) Creatinine-Cystatin C-based CKiD equation (CKiD-eGFR CysC formula). Results We included 23 pediatric HSCT survivors, with a mean (±SD) age of 14.35 (±5.27) years. Most of our patients were diagnosed with aplastic anemia (43.5%) and beta-thalassemia major (26.1%), where HSCT, 87% was allogeneic, 4.3% cord blood; meanwhile 8.7% was autologous. The most common reported complications were AKI (56.5%), and acute Graft-versus-host disease (43.5%), meanwhile, CKD was reported in 4/23 (17.4%) according to serum creatinine bases formulas, and one (4.3%) patient according to serum cystatin C, and two (8.6%) patients based on CKiD-eGFR CysC formula. CKD was linked to the conditioning regimen by Cyclophosphamide and antithymocyte globulin, the use of vancomycin and aminoglycoside, and the history of AKI. Conclusion CKD is not uncommon complications post-transplantation, and is strongly correlated to the previous conditioning regimen, antimicrobials, and history of AKI. The accuracy and early diagnosis of CKD necessitated the use of combined equations of eGFR calculation. CKD Controllable measures are needed to prevent renal insult in children post-transplantation.

Hypertension and Left Ventricular Strain in Pediatric Chronic Kidney Disease.

Left ventricular global longitudinal strain (LV GLS) on echocardiography is a sensitive yet clinically significant marker of myocardial dysfunction. Reduced LV GLS is prevalent in adults with chronic kidney disease and hypertension and is associated with adverse cardiovascular outcomes. It may be a biomarker of chronic kidney disease-associated myocardial dysfunction in children, but data are limited. Our objective was to describe LV GLS in the CKiD study (Chronic Kidney Disease in Children) and to examine the association between blood pressure (BP) and reduced LV GLS. A single apical 4-chamber view was used to estimate LV GLS. Our main analyses examined the association of clinic BP with the absolute value of LV GLS and LV GLS dichotomized at 16. Sensitivity analyses using 24-hour ambulatory BP monitoring data were also performed. Generalized estimating equations were used to account for within-person correlation and to estimate robust SEs for 95% CIs. Covariates in adjusted models included: age, sex, race, estimated glomerular filtration rate, urine protein, hemoglobin, left ventricular hypertrophy, and the use of renin-angiotensin system inhibitors. LV GLS was measured in 962 person-visits. A total of 77 assessments had an LV GLS <16. In adjusted models, both clinic systolic BP (odds ratio, 1.02 [95% CI, 1.01-1.03]) and diastolic BP (odds ratio, 1.02 [95% CI, 1.00-1.03]) percentiles were associated with LV GLS <16. Having awake or nighttime diastolic BP hypertension on ambulatory BP monitoring was significantly associated with a lower absolute value of LV GLS. Office systolic and diastolic hypertension was associated with diminished LV GLS. Only diastolic hypertension detected on ambulatory BP monitoring was associated with lower LV GLS.

KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease in Children and Adults: a commentary from the European Renal Best Practice (ERBP)

ABSTRACT The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Guideline for Identification and Management of Chronic Kidney Disease (CKD) is a welcome development, coming 12 years after the paradigm-changing 2012 guidelines. We are living in an unprecedented era in nephrology with novel therapies, including sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists, now being proven in multiple randomized controlled clinical trials to reduce both the progression of CKD and cardiovascular morbidity and mortality. The KDIGO 2024 CKD Guideline is aimed at a broad audience looking after children and adults with CKD and provide practical and actionable steps to improve care. This commentary reviews the guideline sections pertaining to the evaluation and risk assessment of individuals with CKD from a European perspective. We feel that despite the last guideline being published 12 years ago, and the fact that the assessment of CKD has been emphasized by many other national/international nephrology, cardiology and diabetology guidelines and societies, the diagnosis and treatment of CKD remains poor across Europe. As such, the KDIGO 2024 CKD Guideline should be seen as an urgent call to action to improve diagnosis and care of children and adults with CKD across Europe. We know what we need to do. We now need to get on and do it.

The Impact of Autosomal Dominant Polycystic Kidney Disease in Children: A Nephrological, Nutritional, and Psychological Point of View.

Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disorder characterized by the formation of numerous fluid-filled cysts in the kidneys, leading to progressive renal failure and various extrarenal complications, including hypertension. This review explores the genetic basis of ADPKD, including emerging evidence of epigenetic mechanisms in modulating gene expression and disease progression in ADPKD. Furthermore, it proposes to examine the pathological characteristics of this condition at the nephrological, cardiovascular, nutritional, and psychological levels, emphasizing that the follow-up of patients with ADPKD should be multidisciplinary from a young pediatric age.

Vitamin D and its associations with blood pressure in the Chronic Kidney Disease in Children (CKiD) cohort.

Vitamin D (25OHD) can modulate pathways and mechanisms that regulate blood pressure (BP). Observational studies in children and adults have shown an inverse association between 25OHD and BP. Studies evaluating associations between 25OHD and BP in pediatric chronic kidney disease are limited. We evaluated the associations between 25OHD and BP using data from the Chronic Kidney Disease in Children (CKiD) study. Clinic or ambulatory BP index was defined as participant's BP divided by 95th age-sex-height-specific BP percentile, an index > 1 suggests hypertension. Primary outcomes of interest were changes in systolic and diastolic clinic and ambulatory BP indices over follow-up. Linear mixed-effects models were used to evaluate associations between BP indices and 25OHD. The study cohort consisted of 370 participants who contributed 970 person-visits. A subset of 194 participants with ambulatory BP data contributed 465 person-visits. There was an association between baseline 25OHD levels and clinic systolic BP index such that for every 10ng/ml lower 25OHD, clinic systolic BP index was 1.0% higher (95%CI: 0.2-1.8, p = 0.016) between participants. The association between clinic diastolic BP index with baseline 25OHD was not significant. For within-person changes, longitudinal decreases in 25OHD were not significantly associated with concomitant increases in clinic systolic or diastolic BP index. There were no significant associations between 25OHD levels at baseline or longitudinally with 24-h ABPM indices. Low 25OHD levels were associated with higher clinic systolic BP in children with CKD. Vitamin D supplementation to maintain normal 25OHD levels might be a useful adjunctive treatment in optimizing BP control in these high-risk patients.

The Association Between Markers of Inflammation and the Progression of Chronic Kidney Disease in Children with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

The Association Between Markers of Inflammation and the Progression of Chronic Kidney Disease in Children with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

A Pilot Comparative Study between Creatinine- and Cystatin-C-Based Equations to Estimate GFR and Kidney Ultrasound Percentiles in Children with Congenital Anomalies of the Kidney and Urinary Tract.

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at "Louis Turcanu" Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT.

Consistency of metabolite associations with measured glomerular filtration rate in children and adults.

There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation. We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK). We evaluated metabolite-mGFR correlation association with metabolite class, molecular weight, assay platform and measurement coefficient of variation (CV). Among metabolites with strong negative correlations with mGFR (r < -0.5), we assessed additional variation by age (height in children), sex, race and body mass index (BMI). A total of 561 metabolites (63%) were negatively correlated with mGFR. Correlations with mGFR were highly consistent across study, sex, race and BMI categories (correlation of metabolite-mGFR correlations between 0.88 and 0.95). Amino acids, carbohydrates and nucleotides were more often negatively correlated with mGFR compared with lipids, but there was no association with metabolite molecular weight, liquid chromatography/mass spectrometry platform and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r < -0.5), 27 were consistently not associated with age (height in children), sex or race. The majority of metabolite-mGFR correlations were negative and consistent across sex, race, BMI and study. Metabolites with consistent strong negative correlations with mGFR and non-association with demographic variables may represent candidate markers to improve estimation of GFR.

Assessing bias in GFR estimating equations: improper GFR stratification can yield misleading results.

Assessing bias (estimated - measured) is key to evaluating glomerular filtration rate (GFR). Stratification by subgroups can indicate where equations perform differently. However, there is a fallacy in the assessment of two instruments (e.g., eGFR and mGFR) when stratifying on the level of only one of those instruments. Here, we present statistical aspects of the problem and a solution for GFR stratification along with an empirical investigation using data from the CKiD study. Compared and contrasted biases (eGFR relative to mGFR) with 95% confidence intervals within strata of mGFR only, eGFR only, and the average of mGFR and eGFR using data from the Chronic Kidney Disease in Children (CKiD) study. A total of 304 participants contributed 843 GFR studies with a mean mGFR of 48.46 (SD = 22.72) and mean eGFR of 48.67 (SD = 22.32) and correlation of 0.904. Despite strong agreement, eGFR significantly overestimated mGFR when mGFR < 30 (+ 6.2%; 95%CI + 2.9%, + 9.7%) and significantly underestimated when mGFR > 90 (-12.2%; 95%CI - 17.3%, - 7.0%). Significant biases in opposite direction were present when stratifying by eGFR only. In contrast, when stratifying by the average of eGFR and mGFR, biases were not significant (+ 1.3% and - 1.0%, respectively) congruent with strong agreement. Stratifying by either mGFR or eGFR only to assess eGFR biases is ubiquitous but can lead to inappropriate inference due to intrinsic statistical issues that we characterize and empirically illustrate using data from the CKiD study. Using the average of eGFR and mGFR is recommended for valid inferences in evaluations of eGFR biases.

To Evaluate the Epidemiology, Etiology, Risk Factors and Treatment Management in Chronic Kidney Disease in Children, Adult and Geriatric Patients in a Tertiary Care Teaching Hospital in Nellore

Chronic renal failure is a life-threatening disease to society. The study was conducted from October 2021 to June 2023 the study was done in the Nephrology inpatient ward, Vijaya Super Speciality Hospital, Pogathota Nellore, Andhra Pradesh. The study design is a cross-sectional for epidemiology and prospective observational study-1 for etiology, II-risk factors, III-treatment management. The sample size are 381 subjects in that children are 51 subjects, adult 171 subjects and geriatric are 159 subjects. The male are 199 volunteers and the female are 182 volunteers with chronic kidney disease (CKD). The result of this study was the epidemiology factor more in adults (45%) when compared to children (13%) and geriatrics (42%). In the sex parameters are less affected to females (48%) and males (52%) are more affected with chronic kidney disease. The etiology causes in children are glomerulonephritis, adults diabetes mellitus (DM) and geriatrics pyelonephritis these are the main causes for chronic renal disease when compared to other etiological causes. Risk factors in children are congenital defects, adult are diabetes mellitus and geriatric are kidney disease these are the risk factors to the renal failure patients. In treatment management, hemodialysis is the most effective treatment to adults when compared to children’s and geriatric eng stage renal failure disease. The conclusion of this study initially may rectify causes and risk factors of the patients may not high prevalent in end-stage renal failure disease it not cause hemodialysis therapy and renal transplantation in children, adults and geriatric patients.

The Relationship Between Attention Deficit-Hyperactivity Disorder and Kidney Disease in Children and Adolescents: An Emerging Area of Research

The Relationship Between Attention Deficit-Hyperactivity Disorder and Kidney Disease in Children and Adolescents: An Emerging Area of Research

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

Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression. Nontargeted metabolomics was conducted in plasma samples from 484 Chronic Kidney Disease in Children (CKiD) participants. Multivariable linear regression estimated the cross-sectional association between 949 known, nondrug metabolites and dietary intake of total protein, animal protein, plant protein, chicken, dairy, nuts and beans, red and processed meat, fish, and eggs, adjusting for demographic, clinical, and dietary covariates. Cox proportional hazards models assessed the prospective association between protein-related metabolites and CKD progression defined as the initiation of kidney replacement therapy or 50% eGFR reduction, adjusting for demographic and clinical covariates. One hundred and twenty-seven (26%) children experienced CKD progression during 5years of follow-up. Sixty metabolites were significantly associated with dietary protein intake. Among the 60 metabolites, 10 metabolites were significantly associated with CKD progression (animal protein: n=1, dairy: n=7, red and processed meat: n=2, nuts and beans: n=1), including one amino acid, one cofactor and vitamin, 4 lipids, 2 nucleotides, one peptide, and one xenobiotic. 1-(1-enyl-palmitoyl)-2-oleoyl-glycerophosphoethanolamine (GPE, P-16:0/18:1) was positively associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 88% higher risk of CKD progression. 3-ureidopropionate was inversely associated with dietary intake of red and processed meat, and a doubling of its abundance was associated with 48% lower risk of CKD progression. Untargeted plasma metabolomic profiling revealed metabolites associated with dietary intake of protein and CKD progression in a pediatric population.

Food Insecurity Is Associated with Short Stature, Slow Growth Velocity, and Lower Cognitive Function in the Chronic Kidney Disease in Children (CKiD) Cohort

Food Insecurity Is Associated with Short Stature, Slow Growth Velocity, and Lower Cognitive Function in the Chronic Kidney Disease in Children (CKiD) Cohort

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD.

Children with CKD are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children aged 6 months to 16 years with eGFR 30-90 ml/min per 1.73 m 2 ( n =569). NiCK is a single-center cross-sectional study of participants aged 8-25 years with eGFR<90 ml/min per 1.73 m 2 ( n =60) and matched healthy controls ( n =67). Untargeted metabolomic quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed: intelligence, attention regulation, working memory, and parent ratings of executive function. Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular versus nonglomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, and NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared with healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide-and with intelligence: γ -glutamyl amino acids and aconitate. Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction, and altered energy metabolism, circulating toxins, and redox homeostasis. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_17_CJN0000000000000318.mp3.

A-322 Implementation of Three Age- and Sex-Dependent Equations to Estimate Glomerular Filtration Rates (eGFR) at a Pediatric Institution

Abstract Background The National Kidney Foundation estimates that 37 million people in the United States are affected by kidney disease, although 90% of them are unaware of it. While kidney disease is less common in children and adolescents, early diagnosis and treatment is important due to the significant long-term impact it can have on growth, cognitive development, and cardiovascular disease. Unlike adults, the estimated glomerular filtration rate (eGFR) for pediatric patients is not routinely reported by clinical laboratories. The process of estimating GFR is cumbersome and time-consuming for clinicians, requiring data extraction to use estimating equations with variable accuracy. The Chronic Kidney Disease in Children (CKiD) Study has developed and published new, more precise, estimating equations for use in children and young adults that utilize a sex- and age-dependent constant (k) in conjunction with height and serum creatinine and/or serum cystatin-C. In collaboration with Nephrology and Laboratory Information Technology, we implemented three eGFR equations into our laboratory information system (LIS) and currently report the results in the patient's electronic medical record (EMR). Methods The three equations that were implemented were named eGFR-creatinine (eGFR = k x (height/sCr) with height in m and serum creatinine in mg/dL), eGFR-cystatin (eGFR = k×(1/cysC) with serum cystatin-C in mg/L), and eGFR-average, which reports the average of the creatinine and cystatin-C estimating equations when both are ordered. The k constant is dependent on the patient's age and sex. An eGFR value of &amp;gt;90 mL/min|1.73m2 is considered normal. When an eGFR is ordered, the system identifies the most recent creatinine or cystatin-C result. If one has not been resulted in the last 2 hours, the system reflexes an order for a basic metabolic panel or a cystatin-C. For the eGFR-creatinine equation, the system looks back up to 3 months for a height and uses the most current value. Concordance and discordance were determined in patients who had all three equations ordered and compared as to whether all three values gave a result above or below 90 mL/min|1.73 m2. Results The eGFR-creatinine equation went live in June 2022. As of January 2023, 287 eGFR-creatinine values have been resulted. The cystatin-C assay, eGFR-cystatin equation, and e-GFR average equations went live in November 2022. As of January 2023, 114 eGFR-averages and 167 eGFR-cystatins have been resulted. When both equations were ordered and the eGFR-average was calculated, all three values were concordant 69 times (61%) and discordant 45 times (39%). In 26 instances, the eGFR-creatine value was discrepant compared with the other two equations and in 19 instances, the eGFR-cystatin value was discrepant. The differences between the eGFR equations ranged from 1.1–41.9%, however 65% of the values varied by less than 10% and 88% varied by less than 20%. Conclusion Implementation of pediatric eGFR equations into the LIS and reporting of eGFR in the EMR will allow more accurate assessment of pediatric patients’ kidney function and improved clinician and patient awareness of impaired kidney function. Availability of this information will allow an earlier diagnosis and treatment of chronic kidney disease.

Associations between anemia and FGF23 in the CKiD study

BackgroundFibroblast growth factor 23 (FGF23) is a bone-derived hormone that plays a central role in chronic kidney disease-mineral bone disorder and is associated with CKD progression and cardiovascular morbidity. Factors related to CKD-associated anemia, including iron deficiency, can increase FGF23 production. This study aimed to assess whether anemia and/or iron deficiency are associated with increased circulating concentrations of FGF23 in the large, well-characterized Chronic Kidney Disease in Children (CKiD) study cohort.MethodsHemoglobin concentrations, iron parameters, C-terminal (total) FGF23, intact FGF23, and relevant covariables were measured in cross-sectional analysis of CKiD study subjects.ResultsIn 493 pediatric patients with CKD (median [interquartile range] age 13 [9, 16] years), the median estimated glomerular filtration rate was 48 [35, 61] ml/min/1.73 m2, and 103 patients (21%) were anemic. Anemic subjects had higher total FGF23 concentrations than non-anemic subjects (204 [124, 390] vs. 109 [77, 168] RU/ml, p < 0.001). In multivariable linear regression modeling, anemia was independently associated with higher total FGF23, after adjustment for demographic, kidney-related, mineral metabolism, and inflammatory covariables (standardized β (95% confidence interval) 0.10 (0.04, 0.17), p = 0.002). In the subset of subjects with available iron parameters (n = 191), iron deficiency was not associated with significantly higher total FGF23 concentrations. In the subgroup that had measurements of both total and intact FGF23 (n = 185), in fully adjusted models, anemia was significantly associated with higher total FGF23 (standardized β (95% CI) 0.16 (0.04, 0.27), p = 0.008) but not intact FGF23 (standardized β (95% CI) 0.02 (−0.12, 0.15), p = 0.81).ConclusionsIn this cohort of pediatric patients with CKD, anemia was associated with increased total FGF23 levels but was not independently associated with elevated intact FGF23, suggesting possible effects on both FGF23 production and cleavage. Further studies are warranted to investigate non-mineral factors affecting FGF23 production and metabolism in CKD.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information