Childhood Chronic Kidney Disease Research Articles

Is mild dehydration a risk for progression of childhood chronic kidney disease?

Children with chronic kidney disease (CKD) can have an inherent vulnerability to dehydration. Younger children are unable to freely access water, and CKD aetiology and stage can associate with reduced kidney concentrating capacity, which can also impact risk. This article aims to review the risk factors and consequences of mild dehydration and underhydration in CKD, with a particular focus on evidence for risk of CKD progression. We discuss that assessment of dehydration in the CKD population is more challenging than in the healthy population, thus complicating the definition of adequate hydration and clinical research in this field. We review pathophysiologic studies that suggest mild dehydration and underhydration may cause hyperfiltration injury and impact renal function, with arginine vasopressin as a key mediator. Randomised controlled trials in adults have not shown an impact of improved hydration in CKD outcomes, but more vulnerable populations with baseline low fluid intake or poor kidney concentrating capacity need to be studied. There is little published data on the frequency of dehydration, and risk of complications, acute or chronic, in children with CKD. Despite conflicting evidence and the need for more research, we propose that paediatric CKD management should routinely include an assessment of individual dehydration risk along with a treatment plan, and we provide a framework that could be used in outpatient settings.

Gestational Exposure to Maternal Systemic Glucocorticoids and Childhood Risk of CKD

Background & ObjectivesThe potential effects of antenatal glucocorticoid exposure on the health of children are unclear. We examined the association of gestational exposure to maternal systemic glucocorticoids (SG) and the risk of developing chronic kidney disease (CKD) in childhood. Study designRetrospective cohort study. Setting & ParticipantsNewborns cared for at the largest healthcare delivery system in Taiwan between 2004 and 2018. ExposureMaternal prescriptions for SG between the last menstrual period and birth as a proxy for gestational exposure. OutcomeIncidence of childhood CKD, including congenital anomalies of the kidney and urinary tract (CAKUT) and other kidney diseases (non-CAKUT) over 10 years. Analytical ApproachCox proportional hazards models with stabilized inverse probability of treatment weighting and robust sandwich estimator were used to estimate the average association between SG and incident CKD after adjustment for offspring characteristics (aHR). ResultsAmong 23,363 singleton-born children, gestational SG exposure was significantly associated with a higher risk of childhood CKD (aHR, 1.69 [95% CI, 1.01–2.84]). Stratified analyses showed stronger associations between SG and childhood CKD within the strata of birth <37 weeks gestational age (aHR, 2.38 [95% CI, 1.19–4.78]), male sex (aHR, 1.89 [95% CI, 1.00–3.55]), gestational exposure in the second trimester (aHR, 6.70 [95% CI, 2.17–20.64]), and total dose >24 mg hydrocortisone equivalent (aHR, 1.91 [95% CI, 1.05–3.47). LimitationsStudy was limited to the Taiwan healthcare delivery system and childhood CKD events through age 10 years. ConclusionsThe findings of this study suggest that gestational exposure to systemic glucocorticoids is associated with the occurrence of kidney disease in childhood. If these findings are confirmed, they may inform clinicians who are considering prescribing SG during pregnancy.

Indoxyl Sulfate Contributes to Impaired Height Velocity in (Pre)School Children

IntroductionGrowth failure is considered the most important clinical outcome parameter in childhood chronic kidney disease (CKD). Central in the pathophysiology of growth failure is the presence of a chronic pro-inflammatory state, presumed partly driven by the accumulation of uremic toxins. In this study, we assessed the association between uremic toxin concentrations and height velocity in a longitudinal multicentric prospective pediatric CKD cohort of (pre-)school aged children and children during pubertal stages. MethodsIn a prospective, multicentric observational study, a selection of uremic toxin levels of children (0-18y) with CKD stage 1-5D was assessed every 3 months (max 2 years) along with clinical growth parameters. Linear mixed models with a random slope for age and a random intercept for child were fitted for height (in cm and SDS). A piecewise linear association between age and height was assumed. ResultsData-analysis included data from 560 visits of 81 children (median age 9.4 years; 2/3 male). In (pre-)school aged children (2-12 years), a 10% increase in concurrent indoxyl sulfate (IxS, total) concentration resulted in an estimated mean height velocity decrease of 0.002 SDS/year (p<.05), given that CKD stage, growth hormone, bicarbonate concentration, and dietary protein intake are held constant. No significant association with height velocity was found in children during pubertal stages (>12years). ConclusionsThe present study demonstrated that especially IxS contributes to a lower height velocity in (pre-)school children, while we could not find a role for uremic toxins with height velocity during pubertal stages.

Childhood Obesity: Insight into Kidney Involvement.

This review examines the impact of childhood obesity on the kidney from an epidemiological, pathogenetic, clinical, and pathological perspective, with the aim of providing pediatricians and nephrologists with the most current data on this topic. The prevalence of childhood obesity and chronic kidney disease (CKD) is steadily increasing worldwide, reaching epidemic proportions. While the impact of obesity in children with CKD is less pronounced than in adults, recent studies suggest a similar trend in the child population. This is likely due to the significant association between obesity and the two leading causes of end-stage renal disease (ESRD): diabetes mellitus (DM) and hypertension. Obesity is a complex, systemic disease that reflects interactions between environmental and genetic factors. A key mechanism of kidney damage is related to metabolic syndrome and insulin resistance. Therefore, we can speculate about an adipose tissue-kidney axis in which neurohormonal and immunological mechanisms exacerbate complications resulting from obesity. Adipose tissue, now recognized as an endocrine organ, secretes cytokines called adipokines that may induce adaptive or maladaptive responses in renal cells, leading to kidney fibrosis. The impact of obesity on kidney transplant-related outcomes for both donors and recipients is also significant, making stringent preventive measures critical in the pre- and post-transplant phases. The challenge lies in identifying renal involvement as early as possible, as it is often completely asymptomatic and not detectable through common markers of kidney function. Ongoing research into innovative technologies, such as proteomics and metabolomics, aims to identify new biomarkers and is constantly evolving. Many aspects of pediatric disease progression in the population of children with obesity still require clarification. However, the latest scientific evidence in the field of nephrology offers glimpses into various new perspectives, such as genetic factors, comorbidities, and novel biomarkers. Investigating these aspects early could potentially improve the prognosis of these young patients through new diagnostic and therapeutic strategies. Hence, the aim of this review is to provide a comprehensive exploration of the pathogenetic mechanisms and prevalent pathological patterns of kidney damage observed in children with obesity.

Effects of childhood obesity on heart failure and its associated risk factors in the European population: A Mendelian randomization study

Background and aimsObservational studies have shown that obesity considerably affects the cardiovascular system. Thus we conducted this Mendelian randomization (MR) analysis to evaluate the causal effect of childhood obesity on heart failure (HF) and its risk factors. Methods and resultsWe obtained genetic instruments from genome-wide association studies (GWAS) that investigated childhood obesity, HF, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), chronic kidney disease (CKD), valvular heart disease, myocarditis, hypertrophic cardiomyopathy, and hyperthyroidism. Inverse variance weighting (IVW), weighted median analysis, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were employed for MR analyses. In addition, the leave-one-out sensitivity test, MR-PRESSO global test, and Cochran’s Q test were used for sensitivity analyses. Genetic evaluations showed that childhood obesity increases the risk of HF (odds ratio [OR] = 1.11, 95%CI: 1.05–1.17, p = 1.26 × 10−4), T2DM (OR = 1.17, 95%CI: 1.12–1.23, p = 8.80 × 10−12), AF (OR = 1.08, 95%CI: 1.05–1.12, p = 2.66 × 10−7), MI (OR = 1.08, 95%CI: 1.04–1.13, p = 3.35 × 10−4), and CAD (OR = 1.08, 95%CI: 1.03–1.13, p = 1.48 × 10−3). We found no association between childhood obesity and CKD, valvular heart disease, myocarditis, hypertrophic cardiomyopathy, or hyperthyroidism. Sensitivity analysis and Bonferroni’s correction showed consistent results. ConclusionsOur study provides new evidence for the relationship between childhood obesity and HF and its risk factors. The results indicate that individuals with a history of childhood obesity require more clinical attention to prevent the development of HF.

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.

Hypertension in children with congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of childhood chronic kidney disease (CKD). We hypothesized that hypertension varies across CAKUT categories and increases the risk of CKD. This was a retrospective cohort study and included cases with a multicystic dysplastic kidney (MCDK, n = 81), unilateral kidney agenesis (UKA, n = 47), kidney hypoplasia (KH, n = 130), and posterior urethral valves (PUV, n = 75). Hypertension was defined as systolic or diastolic blood pressure ≥ 95th percentile for age, sex and height, and CKD as an estimated glomerular filtration rate < 60ml/min/1.73 m2, both at 2 consecutive clinic visits at least 3months apart. Sixty-two (19%) out of 333 cases developed hypertension, with significant difference according to CAKUT type. Patients with smaller kidney size (7.7 vs. 8.3, p = 0.045), kidney anomalies in addition to the primary diagnosis (aCAKUT) (53 vs. 38%, p = 0.03), proteinuria (46 vs. 12%, p < 0.001), and CKD (51 vs. 23%, p < 0.001) were more likely to develop hypertension. When adjusted for kidney size, the diagnoses of PUV (OR 10.9, 95%CI 3.0, 40.5), UKA (OR 6.4, 95%CI 1.6, 24.9) and KH (OR 4.2, 95%CI 1.1, 16.1), and aCAKUT (OR 2.1, 95%CI 1.2, 3.9) were independent risk factors for hypertension. Hypertension increased the risk of developing CKD by twofold (HR 1.9, 95%CI 1.19, 2.94). Hypertension is common in children with CAKUT and increases the risk of CKD. These findings will aid in the development of a standardized clinical pathway for the care of hypertensive children with CAKUT.

Kidney Considerations in Pediatric Obesity.

Chronic kidney disease (CKD) is a common condition and a major cause of morbidity and mortality in adults, but children and adolescents are also at risk for early kidney injury and development of CKD. Obesity contributes both directly and indirectly to the development of CKD. The purpose of this review is to describe obesity-related kidney disease (ORKD) and diabetic kidney disease (DKD) and their impact in the pediatric population. Although obesity-related CKD in childhood and adolescence is uncommon, nascent kidney damage may magnify the lifetime risk of CKD. Glomerular hyperfiltration is an early phenotype of both ORKD and DKD and typically manifests prior to albuminuria and progressive decline in GFR. Novel treatments for obesity and type 2 diabetes exerting protective effects on the kidneys are being investigated for use in the pediatric population. It is important to understand the impact of obesity on the kidneys more fully in the pediatric population to help detect injury earlier and intervene prior to the onset of irreversible progression of disease and to guide future research in this area.

Longitudinal changes of health-related quality of life in childhood chronic kidney disease.

Few longitudinal studies have evaluated the impact of chronic kidney disease (CKD) duration on health-related quality of life (HRQOL). The study's aim was to determine how HRQOL changes over time in childhood CKD. Study participants were children in the chronic kidney disease in children (CKiD) cohort who completed the pediatric quality of life inventory (PedsQL) on three or more occasions over the course of two or more years. Generalized gamma (GG) mixed-effects models were applied to assess the effect of CKD duration on HRQOL while controlling for selected covariates. A total of 692 children (median age = 11.2) with a median of 8.3years duration of CKD were evaluated. All subjects had a GFR greater than 15ml/min/1.73 m2. GG models with child self-report PedsQL data indicated that longer CKD duration was associated with improved total HRQOL and the 4 domains of HRQOL. GG models with parent-proxy PedsQL data indicated that longer duration was associated with better emotional but worse school HRQOL. Increasing trajectories of child self-report HRQOL were observed in the majority of subjects, while parents less frequently reported increasing trajectories of HRQOL. There was no significant relationship between total HRQOL and time-varying GFR. Longer duration of the disease is associated with improved HRQOL on child self-report scales; however, parent-proxy results were less likely to demonstrate any significant change over time. This divergence could be due to greater optimism and accommodation of CKD in children. Clinicians can use these data to better understand the needs of pediatric CKD patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Childhood modifiable risk factors and later life chronic kidney disease: a systematic review

BackgroundRelationships between adulthood modifiable risk factors and chronic kidney disease (CKD) are well-established, but associations with childhood risk factors are unclear. This study systematically assesses the published evidence about childhood modifiable risk factors and adulthood CKD.MethodsWe searched MEDLINE, EMBASE, and Web of Science to 6th May 2022. Articles were included if (1) they were population-based longitudinal studies, (2) exposures were potentially modifiable, for example through pharmacological or lifestyle modifications, including clinical conditions/measures (diabetes, blood pressure, adiposity, and dyslipidaemia); health behaviours (smoking, alcohol consumption, physical activity, fitness, and poor nutrition); and socio-economic factors (socio-economic position), and occurred during childhood (ages 2–19 years), and (3) outcome was CKD or surrogate markers of CKD in adulthood (ages 20 years or older). Three reviewers independently extracted the data.Results15,232 articles were identified after deduplication; 17 articles met the inclusion criteria, reporting childhood blood pressure (n = 8), adiposity (n = 4), type 2 diabetes (n = 1), socio-economic position (n = 1), famine (n = 1), cardiorespiratory fitness (n = 1), and a healthy lifestyle score (n = 1). The results suggested positive associations of childhood adiposity, type 2 diabetes, and low socio-economic position and cardiorespiratory fitness in females with CKD in adulthood. Findings were inconsistent on associations between childhood BP and CKD in adulthood. Childhood healthy lifestyle score and exposure to famine were not associated with risk of CKD in adulthood.ConclusionsThe limited evidence suggests childhood factors may contribute to the CKD risk in adulthood, particularly adiposity, type 2 diabetes, and low socio-economic position and cardiorespiratory fitness in females. Further high-quality community-based studies are needed with long-term follow-up and investigation of a broader range of modifiable risk factors.

Predicting outcomes in children with congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most frequent causes of childhood chronic kidney disease (CKD). Using a large CAKUT cohort, we sought to identify the predictors of CKD and to develop a prediction model that informs a risk-stratified clinical pathway. This was a retrospective cohort study including cases with multicystic dysplastic kidneys (MCDK), unilateral kidney agenesis (UKA), kidney hypoplasia (KH), and posterior urethral valves (PUV). We identified risk factors for CKD (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2) and tested their performance in an adjusted multivariate binary regression model. Prediction probability scores for CKD were used to separate cases likely to develop complications from those not needing specialist follow-up. We identified 452 eligible cases of CAKUT with 22% developing CKD. Strongest associations with CKD included primary diagnosis (OR 3.5, 95% CI 2.6-4.6), preterm delivery (OR 2.3, 95% CI 1.2-4.4), non-kidney anomalies (OR 1.8, 95% CI 1.1-3), first eGFR<90 (OR 8.9, 95% CI 4.4-18.1), small kidney size (OR 9, 95% CI 4.9-16.6), and additional kidney anomalies (OR 1.6, 95% CI 1.2-2.8). PUV (OR 4.7, 95% CI 1.5-15.3), first eGFR <90 (OR 4.4, 95% CI 2-9.7), and kidney length to body length ratio <7.9 (OR 4.2, 95% CI 1.9-9.2) were independent predictors of CKD. The regression model had a prediction accuracy of 80% and a prediction probability c-statistic of 0.81. Using a large combined CAKUT cohort we identified risk factors for CKD. Our prediction model provides the first steps towards a risk-stratified clinical pathway. A higher resolution version of the Graphical abstract is available as Supplementary information.

Epidemiology of childhood chronic kidney diseases

Major advances have been made in the management of children with chronic kidney disease (CKD) over the past 30 years. However, existing epidemiological data mainly relies on registries of chronic kidney replacement therapy. The incidence and prevalence of earlier stages of CKD remain largely unknown, but rare population-based studies suggest that the prevalence of all stages CKD may be as high as 1 % of the pediatric population. Congenital disorders including renal hypodysplasia and uropathy (CAKUT) and hereditary nephropathies account for one-half to two-thirds of childhood CKD cases in high-income countries, whereas acquired nephropathies predominate in developing countries. CKD progression is slower in children with congenital disorders than in those with glomerular nephropathy, and other risk factors for progression have also been identified. Children with CKD have poorer health-related quality of life when compared to healthy children. While survival of children with CKD has continuously improved over time, mortality remains 20 to 30 times higher than in the general pediatric population.

A Rare Cause of Hypergonadotropic Hypogonadism: Transaldolase Deficiency in Two Siblings.

Transaldolase deficiency is a rare inborn autosomal recessive disorder caused by biallelic mutations in the TALDO1 gene. It is characterized by intrauterine growth restriction, dysmorphism, abnormal skin, cytopenia, hepatosplenomegaly, liver cirrhosis, endocrine problems, renal and cardiac abnormalities. We present two siblings of Turkish origin with early-onset form of transaldolase deficiency and hypergonadotropic hypogonadism in both sexes. The girl (index) was followed-up with cryptogenic cirrhosis, leukopenia and thrombocytopenia, skin abnormalities, congenital heart defects, hypercalciuria, nephrolithiasis, proteinuria, chronic kidney disease throughout childhood. She developed hypergonadotropic hypogonadism in adolescence period. Whole exome sequencing due to the multisystemic involvement revealed a previously described homozygous inframe deletion in TALDO1 gene. Her brother was born as a small for gestational age baby and was also followed-up with cryptogenic cirrhosis since his infancy, together with cytopenia, congenital heart defects, bilateral cryptorchidism, short stature, hypercalciuria, proteinuria and chronic kidney disease in childhood. He presented with testicular microlithiasis and hypergonadotropic hypogonadism in adolescence. Sanger sequencing of TALDO1 gene confirmed the presence of the same homozygous deletion with his sister. The mother was found to be a heterozygous carrier for this deletion. We describe two patients with multisystemic involvement since neonatal period who presented with an additional hypergonadotropic hypogonadism in adolescence. The diagnosis of transaldolase deficiency should be kept in mind for these patients, and they must be evaluated for gonadal functions especially during puberty.

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.

Risk factors for childhood chronic kidney disease: a population-based study.

The population-based prevalence and risk factors of childhood chronic kidney disease (CKD) are not well-defined. We ascertained childhood CKD epidemiology and perinatal risk factors, based on a large computerized medical record database that covers most of southern Israel's population. Pre- and post-natal records of 79,374 eligible children (with at least one serum creatinine test) born during 2001-2015 were analyzed. "Ever-CKD" was defined as ≥ 2 estimated glomerular filtration rate (eGFR) values < 60ml/min/1.73 m2 beyond age 2years, more than 3months apart. The last CKD status was determined on March 2019. Of 82 (0.1%) patients with ever-CKD, 35 (42.7%) had their first abnormal eGFR identified already at age 2years. In multiple logistic regression analysis, congenital anomalies of kidney and urinary tract (CAKUT)-related diagnoses, glomerulopathy, maternal oligohydramnios, small for gestational age, prematurity (under 34weeks), post-term delivery, and small for gestational age at birth were significant risk factors for ever-CKD (odds ratio (95% confidence interval): 44.34(26.43-74.39), 64.60(32.42-128.70), 5.54(3.01-10.19), 2.02(1.25-3.28), 4.45(2.13-9.28), 2.96(1.28-6.86 and 2.02(1.25-3.28), respectively). Seventy children with ever-CKD (85.4%) had a depressed eGFR (< 90ml/min/1.73 m2) on the last assessment (current-CKD), yielding a prevalence of 882/million. CKD is more prevalent among children in southern Israel than previously reported, even after excluding those with aborted-CKD. Prenatal conditions increase the risk to develop CKD in childhood. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

Hydrogen Sulfide-to-Thiosulfate Ratio Associated with Blood Pressure Abnormalities in Pediatric CKD.

Identifying children with chronic kidney disease (CKD) at high risk of cardiovascular disease (CVD) and ensuring they receive appropriate treatment can prevent CVD events and mortality later in life. Hydrogen sulfide (H2S) is a gaseous signaling molecule participating in CVD and CKD. Thiosulfate is not only an oxidation product of H2S but is also a H2S donor. We examined whether H2S, thiosulfate, and their combined ratio have differential associations with CVD risk markers in 56 children and adolescents aged 6–18 years with CKD stages G1–G4. Up to two-thirds of CKD children showed higher BP load on 24 h ambulatory blood pressure monitoring (ABPM), even in the early stage. CKD children with ABPM abnormalities had a higher H2S-to-thiosulfate ratio, while H2S-related parameters were not affected by the severity of CKD. The H2S-to-thiosulfate ratio was positively correlated with 24 h systolic BP (SBP), nighttime SBP, and carotid artery intima-media thickness (cIMT). After adjusting for confounders, H2S was negatively associated with LV mass, thiosulfate was positively associated with 24-DBP, and the H2S-to-thiosulfate ratio was positively correlated with nighttime SBP and cIMT. Our data demonstrate differential associations in circulating H2S, thiosulfate, and their combined ratio with CVD risk in childhood CKD. Further studies are required to determine whether targeting the H2S signaling pathway can develop novel therapeutic strategies against CVD in this high-risk population.

Hemostasis and oxidative stress in chronic kidney disease in children and adolescents.

Chronic kidney disease (CKD) can be defined as the progressive loss of renal function, characterized by a decreased glomerular filtration rate (GFR). The etiology of CKD in childhood is mainly associated with congenital anomalies of the kidneys and urinary tract (CAKUT) and with glomerular diseases. The goal of this study was to investigate the hemostasis and oxidative stress in pediatric CKD of different etiologies. Fifty-four CKD children and adolescents and 52 controls were enrolled in this study. The evaluation of hemostasis was carried out by determination of D-dimer (D-Di) and plasminogen activator inhibitor (PAI-1) plasma levels, while oxidative stress was evaluated by thiobarbituric acid reactive substance (TBARS) levels, protein carbonyl content, plasma antioxidant capacity (MTT), and ascorbate. The D-Di was increased in CAKUT stage 3 or 4 patients compared with those with glomerular disease. PAI-1 was increased in patients with glomerular disease compared with CAKUT. Carbonyl protein content was higher in the control group compared with glomerular disease stage 3 or 4 patients. Our findings showed that the reduction in GFR is associated with a state of hypercoagulability. The analysis of integrated networks showed an expansion of connections among hemostatic and oxidative stress markers in CKD children and adolescents compared with controls.

FC039: Associations between Maternal Antenatal Systemic Glucocorticoids Usage and Childhood Chronic Kidney Disease

Abstract BACKGROUND AND AIMS The effect of antenatal glucocorticoid exposure on offspring health is currently unclear. Therefore, this study examined the association of maternal exposure to systemic glucocorticoids in the past and during pregnancy with the risk of chronic kidney disease (CKD) development in childhood. Methods A retrospective cohort study of maternal-child dyads was identified from the largest healthcare delivery system in Taiwan between 1 January 2004 and 31 December 2018. Primary analyses were used to compare past and gestational exposures with non-exposure to systemic glucocorticoid considering an inverse probability of treatment weight to adjust the hazard ratio of offspring CKD development in singleton child-matched pairs. Offspring birthweight, sex, gestational weeks stratified analyses and sibling-matched sensitivity analyses were performed to ensure the robustness of the primary study results. RESULTS In a cohort with 31 927 singleton born children, the cumulative incidence of CKD was 2.23% (n = 713), with 3.18% (n = 63) in the gestational glucocorticoid-exposed group, 1.91% (n = 58) in the past exposed group and 2.2% (n = 592) in the non-exposed group. Gestational exposure, compared with non-exposure, was significantly associated with a higher risk of childhood CKD (inverse probability therapeutic weighted hazard ratio [wHR], 1.42 [95% confidence interval (95% CI) 1.05–1.92] in Figure. 1A, but not past exposure (wHR: 0.89, 95% CI 0.67–1.18) (Figure. 1B). In male children, the risk of CKD was significantly higher among gestational-exposed children than among unexposed children (wHR: 1.72, 95% CI 1.21–2.43). The cohort with sibling matched children did not show a significantly increased risk of childhood CKD associated with gestational exposure (wHR: 1.31, 95% CI 0.79–2.18) (Figure. 1A). CONCLUSION Maternal gestational glucocorticoid treatment was found to be significantly associated with CKD development in children. These findings may support clinicians in performing benefit-risk assessment and in decision-making for systemic glucocorticoid treatment during pregnancy, in clinical settings.

Pediatric Patients Undergoing a Fontan Operation or with a High RACHS-1 Score Require Monitoring for Chronic Kidney Disease in Early Childhood.

Although the number of pediatric patients with long-term survival following cardiac surgery is increasing, concerns regarding chronic kidney disease (CKD) after surgery are growing. We examined the frequency of and risk factors for pediatric CKD development in patients with congenital heart disease (CHD) at least 2years after cardiac surgery. This was a cross-sectional study of 147 patients who underwent open-heart surgery for CHD at Kagoshima University Hospital from April 2010 to March 2017. Data on demographics, acute kidney injury after cardiac surgery, cyanotic heart disease, Fontan circulation, medications in the perioperative period, and Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) category were recorded. CKD was defined using the current classification system described in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative and assessed during early childhood within 2-3years of cardiac surgery. Statistical analyses were performed using SPSS Statistics for Windows version 25.0. We consecutively enrolled 147 patients, of whom 22 (15.0%) had CKD, all with stage-2 severity. Among patients with CKD, a higher proportion underwent Fontan surgery (P < 0.001), a higher proportion had cyanotic heart disease (P = 0.009), and the RACHS-1 category was high (P = 0.003). Patients with CKD appeared more frequently than patients without CKD in RACHS-1 categories 3, 5, and 6. It is essential to evaluate renal function longitudinally and monitor for CKD, given that patients who underwent Fontan surgery or complicated surgery in infancy have a high rate of developing postoperative CKD in early childhood.

Could CA 19-9 be a useful biomarker in the diagnosis, prognosis, and prediction of adequate relief in lower urinary tract obstructions?

posterior urethral valves represent an important cause of childhood chronic kidney disease. The identification of biomarkers that indicate early kidney damage and even adequate clearance could reduce how many patients head towards kidney failure. this study evaluated how this easy-analysis biomarker (CA 19-9) could help identifying potential renal damage and adequate clearance in obstructive uropathies. 46 female Wistar rats were divided into 5 groups, with different patterns of partial urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, obstruction relief 7 postoperative days later; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The CA 19-9s performance was compared to another biomarker: Ngal. Determination of basal CA 19-9 and Ngal in urine and blood and serum creatinine levels was performed in the rats prior to surgery (T0) and after 14 days (T1). Group OIVd underwent intermediate (Ti) collection before clearance. the urinary concentration of CA 19-9 increased in groups OIV, OIVd and OUb; elevation at T1 and Ti, reached statistical significance compared to the T0 value (p<0,05). Changes in urinary CA 19-9 were more expressive in infravesical obstruction groups (AUC 0.81). Obstruction relief in group OIVd promoted significant urinary CA 19-9 reduction (p<0,05) in the final evaluation. CA 19-9 urinary concentration increased in partial urinary tract obstruction. Its best performance was in the bladder neck obstruction group, in which the elevation was detected early (6 days after infravesical obstruction) and the CA19-9 urinary concentration declined after clearance.