Chronic Kidney Disease In Children Research Articles

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.

Longitudinal plasma metabolome patterns and relation to kidney function and proteinuria in pediatric chronic kidney disease.

Understanding plasma metabolome patterns in relation to changing kidney function in pediatric chronic kidney disease (CKD) is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions. There is a limited number of studies of longitudinal metabolomics, and virtually none in pediatric CKD. The Chronic Kidney Disease in Children (CKiD) study is a multi-institutional, prospective cohort that enrolled children aged six-months to 16-years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2. Untargeted metabolomics profiling was performed on plasma samples from the baseline, two-, and four-year study visits. There were technologic updates in the metabolomic profiling platform used between the baseline and follow-up assays. Statistical approaches were adopted to avoid direct comparison of baseline and follow-up measurements.To identify metabolite associations with eGFR or urine protein:creatinine (UPCR) among all three timepoints, we applied linear mixed effects (LME) models. To identify metabolites associated with time, we applied LME models to the two- and four-year follow-up data. We applied linear regression analysis to examine associations between change in metabolite level over time (∆level) and change in eGFR (∆eGFR) and UPCR (∆UPCR). We reported significance based on both the False Discovery Rate (FDR) <0.05 and p<0.05. There were 1156 person-visits (N: baseline=626, 2-year=254, 4-year=276) included. There were 622 metabolites with standardized measurements at all three timepoints. In LME modeling, 406 and 343 metabolites associated with eGFR and UPCR at FDR<0.05 respectively. Among 530 follow-up person-visits, 158 metabolites showed differences over time at FDR<0.05. For participants with complete data at both follow-up visits (N=123), we report 35 metabolites with ∆level∼∆eGFR associations significant at FDR<0.05. There were no metabolites with significant ∆level∼∆UPCR associations at FDR<0.05. We report 16 metabolites with ∆level∼∆UPCR associations at p<0.05 and associations with UPCR in LME modeling at FDR<0.05. We characterized longitudinal plasma metabolomic patterns associated with eGFR and UPCR in a large pediatric CKD population. Many of these metabolite signals have been associated with CKD progression, etiology, and proteinuria in previous CKD Biomarkers Consortium studies. There were also novel metabolite associations with eGFR and proteinuria detected.

Prospective observational study on clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children in central India: A study protocol

Background Congenital anomalies of the kidney and urinary tract (CAKUT) are a group of structural abnormalities affecting these vital organs, frequently leading to chronic kidney disease in children. This study aims to comprehensively understand the clinical profile of CAKUT in children in Central India, an area with unique socio-demographic characteristics and limited prior research on this topic. Methods A prospective observational study will be conducted over three years in the pediatric department of AVBRH, a tertiary healthcare center in Central India. Data were collected through interviews with parents or guardians of children up to 18 admitted to the hospital. Clinical symptoms, prenatal history, physical examinations, and diagnostic investigations were meticulously documented. Expected outcome The study is expected to reveal the prevalence and clinical profile of CAKUT in Central Indian children. Anticipated outcomes include insights into anomalies, clinical symptoms, and potential correlations with factors like prenatal care and consanguineous marriages. Diagnostic investigations will help assess the severity of renal impairment. The results may also uncover regional variations and have implications for public health initiatives aimed at early intervention and improved patient care. However, these are preliminary expectations that are subject to confirmation through the completion of the study.

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

Abstract Background and hypothesis 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. Methods 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 &amp;lt; −0.5), we assessed additional variation by age (height in children), sex, race, and BMI. Results 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 to lipids, but there was no association with metabolite molecular weight, LC/MS platform, and measurement CV. Among 114 metabolites with strong negative associations with mGFR (r&amp;lt;−0.5), 27 were consistently not associated with age (height in children), sex, or race. Conclusions 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.

Unraveling chronic kidney disease in children: a surprising manifestation of celiac disease.

Celiac disease, firstly described in children, is a type of T-cell enteropathy that occurs in individuals genetically predisposed to gluten exposure. The estimated global prevalence of celiac disease is continuously increasing. Although, traditionally, celiac disease was diagnosed in children with failure to thrive and digestive issues, it is now recognized that may present with a wide range of symptoms beyond gastrointestinal ones. Celiac disease continues to pose significant challenges due to the continuous advancement of knowledge in understanding its pathophysiology, diagnosing the condition, managing its effects, and exploring potential therapeutic approaches. The prevalence of celiac disease is increased among individuals with chronic kidney disease, also. The most frequent associations are with diabetic nephropathy, IgA nephropathy and urolithiasis. A gut-kidney axis has been recognized to play a significant role in chronic kidney diseases. This literature review aims to review the chronic renal pathology associated with celiac disease, with emphasis on childhood.

[Research on pediatric hereditary kidney disease: from now to the future].

Hereditary kidney disease is an important cause of chronic kidney disease in children. With the progress of genome sequencing, single-cell technology, and organoid cultures, the research on hereditary kidney disease has entered a new era. How to integrate big data resources, discover new disease-causing genes, and develop effective treatment methods will be the focus of future research. This article discusses the classification, research progress, challenges and prospects of pediatric hereditary kidney disease, so as to provide valuable insights into the research of hereditary kidney disease in children.

WCN24-1496 Prevalence and risk factors associated with chronic kidney disease in children living in a high incidence community in Jalisco, Mexico

WCN24-1496 Prevalence and risk factors associated with chronic kidney disease in children living in a high incidence community in Jalisco, Mexico

Clinical Profile of Pediatric Patients with Steroid-resistant Nephrotic Syndrome Treated by Cyclophosphamide, Cyclosporin A, Mycophenolate Mofetile and Tacrolimus in Hasan Sadikin General Hospital

BackgroundSteroid-resistant nephrotic syndrome is a major cause of chronic kidney disease in children and adolescents. These diseases require appropriate management, while in some developing countries, the availability of agents recommended by international guidelines is very limited.Research objectivesTo determine and describe the patient profiles of pediatric Steroid Resistant Nephrotic Syndrome (SRNS) that use Cyclophosphamide(CPA), Cyclosporine(CyA), Tacrolimus, and Mycofenolat Mofetil (MMF) in Dr. Hasan Sadikin Hospital (RSHS), Bandung as a tertiary hospital in West Java, Indonesia.Methods and materialsThis research used a retrospective study with cross-sectional study design, total sampling method and medical record of pediatric (1-18 years old) patients from January 1st 2017–September 31st 2019 who were diagnosed as SRNS .Results : From 99 subjects that belonged to inclusion criteria, 35.4% pediatric SRNS patients were in the age group 6-10 years and 60.6% were males. Laboratorium profiles showed among all population, ureum &lt;100 mg/dL were found as high as 97%, creatinine 0.3-1.0 mg/dL (71.7%)  albumin &gt;2,5 gr/dL (51.5%), negative hematuria (68.7%) , protein dipstick &lt; 3 (50.5%), and LFG &gt; 90 mL/min/1.73 m2 (79.8%).. The patients generally had use CPA (87.9%) and remission &lt;6 month (51.5%).Conclusion: Profiles of pediatric patients are important to diagnose and prognose SRNS. By using these approaches, it is feasible to access and detect the most effective treatment for SRNS.

Evaluation of eGFR methods in a sub-Saharan African community-based pediatric population.

Accurate assessment of the estimated glomerular filtration rate (eGFR) plays a pivotal role in the early detection, management, and optimal medication dosing for chronic kidney disease (CKD). However, validation of eGFR, utilizing cystatin C-based equations, is limited in African children and adolescents with CKD. We evaluate the agreement of eGFR equations incorporating both cystatin C and creatinine in this specific population. This community-based study assessed CKD in children (2-15years) using cystatin C and serum creatinine. eGFR agreement with the reference was evaluated with Bland-Altman plots, ROC curves, and Lin's CCC, using the Under-25 serum creatinine-cystatin C equation as the reference standard. Pairwise ROC comparisons assess the statistical differences in estimation equation agreement. Among 666 children (mean age, 7.8 ± 3.8years; 48.6% male), CKD prevalence was 11.6% (95% CI, 9.2-14.2%). Notably, the Chehade equation, using combined biomarkers, aligned best with the reference, displaying the lowest mean deviation (- 0.59; 95% CI, - 1.19 to 0.01), superior agreement (P10, 91.0%; P30, 96.70%), and highest discriminatory power (0.989). In contrast, CKD-EPI 2012 cystatin C had the highest mean deviation (- 35.90) and lowest discriminatory power (0.79). Equations combining creatinine and cystatin C (Schwartz, Chehade, Full Age Spectrum) demonstrated strong positive Lin's CCC with CKiD U25 creatinine-cystatin C, while Bouvet showed a notably weak correlation (Lin's CCC, 0.22). In African children with CKD, the Chehade, CKiD Under 25 creatinine-based equations, and the Full Age Spectrum equations show promise for CKD diagnosis. However, a measured GFR is essential to identifying the most accurate eGFR equation in this population.

Arterial hypertension as a risk factor for the development of CKD in children with CAKUT syndrome and its correction

The review is devoted to the development of end-stage renal failure (ESRD) in children with congenital anomalies of the kidneys and urinary tract (CAKUT syndrome. In this regard, measures to slow the progression of chronic kidney disease (CKD) are important. One of the independent risk factors for a decrease in excretory renal function is arterial hypertension (AH), the correction of which is a mandatory component of nephroprotection. CAKUT syndrome is associated with a congenital decrease of the mass of active nephrons, which inevitably leads to hyperfiltration, the main cause of the development of ESRD has a high prevalence in CACUT syndrome and plays a special role in maintaining hyperfiltration. The presence of cysts, nephrosclerosis sites, and endothelial dysfunction contribute to the activation of renin secretion with a further increase in the role of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II is not only a powerful vasoconstrictor. Its effects on sympathetic stimulation of dense spot, hyperplasia of smooth muscle cells, increased expression of several growth factors, cytokines and chemokines is known. The result of the interaction of this complex is the development of glomerular hypertrophy, tubulointerstitial inflammation and fibrosis. Blood pressure correction should begin with lifestyle modification. It is recommended to start taking antihypertensive drugs in children with blood pressure &gt; 90 percentile. Among the first-line pharmacological drugs for the treatment of hypertension, angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II type I receptor blockers (ARBs) play a major role. Unlike adults, a combination of them is possible.

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.

ВРОЖДЕННЫЙ (АНТЕНАТАЛЬНЫЙ) ГИДРОНЕФРОЗ-МОДИФИЦИРУЕМЫЙ ФАКТОР РИСКА ХРОНИЧЕСКОЙ БОЛЕЗНИ ПОЧЕК У ДЕТЕЙ: МЕЖДИСЦИПЛИНАРНЫЙ ПОДХОД В КОНТЕКСТЕ ПРОФЛАКТИКИ ХРОНИЧЕСКОГО ЗАБОЛЕВАНИЯ (ОБЗОР ЛИТЕРАТУРЫ И СОБСТВЕННЫЕ ДАННЫЕ)

Congenital hydronephrosis (CHN) is the most common malformation of the kidney which leads to the development of chronic kidney disease (CKD) in children up to its terminal stage. Current clinical practices related to observation and analysis of long-term outcome of the disease and interdisciplinary collaboration are in the need for further improvement. The purpose of the research was to determine whether CHN is a modifiable risk factor for the onset and progression of CKD in children. Materials and methods used: a single-center cohort retrospective study of the results of antenatal screening of fetuses with congenital defects of organs and systems both with CAKUT syndrome and CHN was conducted at the Samara Oblast Regional Clinical Hospital named after V.D. Seredavin (Samara, Russia) in 2013-2022. Results: 13,484 fetuses were registered with congenital malformations of organs and systems, of which 2,818 (20.9% [20.2%; 21.6%]) with those of urinary organs. 390 were born alive with CHN (13.8% [12.6%; 15.2%]), of which 359 (92%) had surgical intervention using Heinz-Andersen method at the age of 37 [0.3-44.5] weeks: 208 (58%) boys/151 (42%), girls; unilateral CHN in 345 (96%) and bilateral in 14 (4%). Recovery occurred in 328 (91.4% [88.0%; 93 ,9%]) cases with CHN after the surgery. Based on the results of the research, an algorithm for interdisciplinary interaction of healthcare specialists was developed for routing of the pregnant women with fetal CAKUT syndrome. Conclusion: CHN is a modifiable risk factor for the development of CKD since 91.4% of children recovered in the long term.

Depressive disorders in children with chronic kidney disease treated conservatively.

Children with chronic kidney disease (CKD) experience a lot of mental and emotional stress, which can lead to the development of depressive disorders. The prevalence of depressive disorders in CKD children is estimated to be between 7% and 35%. The aim of our study was to analyze the prevalence and characteristics of depression and depressive symptoms in children and adolescents with CKD treated conservatively. The cross-sectional, multicenter study was conducted in 73 CKD children aged 8-18 and in 92 of their parents. To assess the mental wellbeing of CKD children, Kovacs's Children's Depression Inventory 2 (CDI2) was used as CDI2: Self-Report and CDI2: Parent Form. The majority of CKD children acquired medium scores in CDI2, 11% of participants reported symptoms suggesting depressive disorder, and among them 8.2% met the criteria for depression. A significant relationship was found between age and interpersonal problems, age at CKD diagnosis, and total score and ineffectiveness, CKD duration and total score/emotional problems. Depressive symptoms were associated with the stage of CKD, and they differed significantly between stages III and IV. We noticed the child-parent disagreement on reported depressive symptoms. Parents perceive their children's mental state as worse than the children themselves. There is a problem of depression in children with CKD treated conservatively. Variables associated with depressive symptoms in CKD children treated conservatively require further study. Key factors predisposing to the development of depression seem to be age at the time of diagnosis, disease duration, and progression of CKD from stage III to IV. Disparities between depressive symptoms self-reported by CKD children and their parents' assessment require further analysis. However, these disparaties indicate that the final diagnosis of the occurrence of depressive disorders should be based on a multidimensional assessment of the patient's situation.

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.

Global, Regional, and National Burden of CKD in Children and Adolescents from 1990 to 2019.

CKD is one of the most prevalent non-communicable health concerns in children and adolescents worldwide; however, data on its incidence, prevalence, disability-adjusted life years (DALYs), and trends in the population are limited. We aimed to assess the global, regional, and national trends in CKD burden in children and adolescents. In this trend analysis based on the 2019 Global Diseases, Injuries, and Risk Factors Study, CKD incidence, prevalence, and DALYs rates per 100,000 population for children and adolescents were reported at the global, regional, and national levels, as well as the average annual percentage change (AAPC). These global trends were analyzed by age, sex, region, and socio-demographic index (SDI). Globally, the overall incidence of CKD (all stages including KRT) in children and adolescents showed an increasing trend (AAPC 0.44 [95% CI 0.36-0.52]) between 1990 and 2019. Similarly, the overall prevalence of CKD also showed an upward trend (AAPC 0.46 [95% CI 0.42-0.51]). However, the DALYs of CKD showed a continuous decreasing trend (AAPC -1.18[-1.37- -0.99]). The population aged 15-19 years had the largest CKD incidence increase during this period. The largest increase in age-standardized incidence rate (ASIR) was in middle SDI countries (AAPC 0.56 [0.45-0.67]). The relationship between the ASIR and SDI showed an inverse U-shaped correlation while the relationship between the age-standardized DALYs rate (ASDR) and SDI showed an inverse trend with SDI. Among adolescents (15-19 years), the ASIR continued to increase for five causes of CKD, owing to type 2 diabetes mellitus and hypertension. Most of the disease burden was concentrated in countries with a lower SDI. Andean Latin America and Central Latin America showed the largest increases in CKD ASIR between 1990 and 2019. The burden of CKD in children and adolescents has increased worldwide, especially in regions and countries with a lower SDI.

Plasma and Urinary Platelet Factor 4 as Biomarkers for Cardiovascular Risk in Children with Chronic Kidney Disease.

Children suffering from chronic kidney disease (CKD) have a high risk of cardiovascular disease (CVD). The early detection and diagnosis of subclinical CVD in pediatric CKD can reduce mortality later in life. Plasma factor 4 (PF4) is a chemokine released by activated platelets. We examined whether or not PF4 in the plasma and urine, its kidney function normalized ratio, and fractional excretion have differential associations with CVD risk markers in 139 youths aged 3 to 18 years old with CKD stages G1-G4. Significant negative correlations were observed between plasma PF4 and cardiovascular surrogate markers, such as the left ventricular mass index (LVMI), carotid intima-media thickness (cIMT), and pulse wave velocity (PWV). The plasma PF4/creatinine (Cr) ratio was lower in CKD children with a high daytime BP and 24 h BP, high BP load, and nocturnal non-dipping status. After adjusting for confounders, the plasma PF4 and plasma PF4/Cr ratio still independently predicted an abnormal ABPM profile. In addition, both the plasma PF4 and plasma PF4/Cr ratio presented a negative correlation with the L-arginine and asymmetric dimethylarginine ratio. These findings provide convincing evidence supporting the link between PF4 and CVD markers in pediatric CKD. Our study highlights the importance of further research to assess the performance of PF4-related biomarkers in predicting CVD events and CKD progression in children with CKD.

Characteristics and predictors of chronic kidney disease in children with myelomeningocele: a nationwide cohort study.

Myelomeningocele (MMC) is highly prevalent in developing countries, and MMC-related neurogenic bladder is an important cause of childhood chronic kidney disease (CKD). This nationwide study aimed to evaluate demographic and clinical features of pediatric patients with MMC in Turkey and risk factors associated with CKD stage 5. Data from children aged 0-19years old, living with MMC in 2022, were retrospectively collected from 27 pediatric nephrology centers. Patients > 1year of age without pre-existing kidneyabnormalities were divided into five groups according to eGFR; CKD stages 1-5. Patients on dialysis, kidney transplant recipients, and those with eGFR < 15ml/min/1.73 m2 but not on kidney replacement therapy at time of study constituted the CKD stage 5 group. A total of 911 (57.8% female) patients were enrolled, most of whom were expectantly managed. Stages 1-4 CKD were found in 34.3%, 4.2%, 4.1%, and 2.4%, respectively. CKD stage 5 was observed in 5.3% of patients at median 13years old (range 2-18years). Current age, age at first abnormal DMSA scan, moderate-to-severe trabeculated bladder on US and/or VCUG, and VUR history were independent risk factors for development of CKD stage 5 (OR 0.752; 95%; CI 0.658-0.859; p < 0.001; OR 1.187; 95% CI 1.031-1.367; p = 0.017; OR 10.031; 95% CI 2.210-45.544; p = 0.003; OR 2.722; 95% CI 1.215-6.102; p = 0.015, respectively). Only eight CKD stage 5 patients underwent surgery related to a hostile bladder between 1 and 15years old. MMC-related CKD is common in childhood in Turkey. A proactive approach to neurogenic bladder management and early protective surgery in selected cases where conservative treatment has failed should be implemented to prevent progressive kidney failure in the pediatric MMC population in our country.

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.

Systemic Immune Inflammation Index as a Key Predictor of Dialysis in Pediatric Chronic Kidney Disease with the Use of Random Forest Classifier.

Low-grade inflammation is a significant component of chronic kidney disease (CKD). Systemic immune inflammation index (SII), a newly defined ratio combining neutrophil, lymphocyte, and platelet counts, has not yet been evaluated in the pediatric CKD population nor in the context of CKD progression or dialysis. Thus, this study aimed to analyze the complete blood cell count (CBC)-driven parameters, including SII, in children with CKD and to assess their potential usefulness in the prediction of the need for chronic dialysis. A single-center, retrospective study was conducted on 27 predialysis children with CKD stages 4-5 and 39 children on chronic dialysis. The data were analyzed with the artificial intelligence tools. The Random Forest Classifier (RFC) model with the input variables of neutrophil count, mean platelet volume (MPV), and SII turned out to be the best predictor of the progression of pediatric CKD into end-stage kidney disease (ESKD) requiring dialysis. Out of these variables, SII showed the largest share in the prediction of the need for renal replacement therapy. Chronic inflammation plays a pivotal role in the progression of CKD into ESKD. Among CBC-driven ratios, SII seems to be the most useful predictor of the need for chronic dialysis in CKD children.

Association of Ischemia-Modified Albumin (IMA) in Saliva, Serum, and Urine with Diagnosis of Chronic Kidney Disease (CKD) in Children: A Case-Control Study.

BACKGROUND Ischemia-modified albumin (IMA) is a secreted biomarker for ischemic oxidative stress. This case-control study aimed to evaluate the association of ischemia-modified albumin (IMA) in saliva, serum, and urine with diagnosis of chronic kidney disease (CKD) in 24 children. MATERIAL AND METHODS The study involved 24 children with CKD. CKD was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic criteria. The control group consisted of 24 healthy children who were matched for age and gender to the experimental group. The concentration of IMA was determined by the colorimetric method in non-stimulated whole saliva (NWS), stimulated whole saliva (SWS), serum, and urine of children with CKD. The Mann-Whitney U test was used for inter-group comparisons. RESULTS IMA levels were significantly higher in NWS (P=0.0082) and SWS (P=0.0014) of children with CKD than in the control group. The concentration of IMA in NWS was correlated with standard indicators of kidney function, including the estimated glomerular filtration rate (r=-0.798, P≤0.0001), stage of CKD (r=0.814, P≤0.0001), and serum creatinine (r=0.711, P≤0.0001) and urea levels (r=0.738, P≤0.0001). CONCLUSIONS Salivary IMA concentration depends on renal function in children. Salivary IMA discriminates children with end-stage kidney disease from children with mild and moderate CKD and healthy children with high sensitivity and specificity. Further research is required, including assessment of the diagnostic usefulness and validation of the biomarker in a clinical diagnostic study.