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Development of clinical guidelines and recommendations to address the care of pediatric patients with chronic kidney disease (CKD) have rarely included the perspectives of providers from a variety of healthcare disciplines or the patients and parents themselves. Accordingly, the National Kidney Foundation hosted an in-person, one and one-half day workshop that convened a multidisciplinary group of physicians, allied healthcare professionals, and pediatric CKD patients and their parents, with the goal of developing key clinical recommendations regarding best practices for the clinical management of pediatric patients living with CKD. The key clinical recommendations pertained to five broad topics: Addressing the Needs of Patients and Parents/Caregivers; Modifying the Progression of CKD; Clinical Management of CKD-Mineral Bone Disorder and Growth Retardation; Clinical Management of Anemia, Cardiovascular Disease and Hypertension; and Transition and Transfer of Pediatric Patients to Adult Nephrology Care. This report describes the recommendations generated by the participants who attended the workshop.

BACKGROUND: Nocturnal hypertension is a risk factor for chronic kidney disease (CKD) progression among adults. In children, effects of nocturnal hypertension on CKD progression is less studied. METHODS: We investigated the relationships between nocturnal, daytime, or sustained hypertension and progression to kidney replacement therapy in children using Cox proportional hazards models. Nocturnal and diurnal hypertension respectively defined as: mean blood pressure >95th percentile and/or load >25% for either systolic or diastolic blood pressure within sleep or wake periods. RESULTS: One thousand five hundred seventy-seven ambulatory blood pressure monitoring studies from 701 CKiD participants were reviewed. Nighttime, daytime, and both types of hypertension were 19%, 7%, and 33%, respectively. Participants with both daytime and nocturnal hypertension had the highest risk of kidney replacement therapy. Among children with CKD, compared with those who were normotensive, those with isolated nocturnal hypertension had a hazard ratio of 1.49 ([CI, 0.97–2.28]; P =0.068) while those with both daytime and nocturnal hypertension had a HR of 2.23 ([CI, 1.60–3.11]; P CONCLUSIONS: The presence of both daytime and nocturnal hypertension is significantly associated with risk of kidney replacement therapy. Our study confirms the utility of ambulatory blood pressure monitoring in children with CKD. Identifying and controlling both daytime and nocturnal hypertension using ambulatory blood pressure monitoring may improve outcomes and delay CKD progression in this population.

Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking.This retrospective cohort study utilized data from PEDSnet, a national network of pediatric health systems with standardized electronic health record data for more than 6.5 million patients from 2009 to 2021. Incidence rates (per 10,000 person-years) of fracture, slipped capital femoral epiphysis (SCFE), and avascular necrosis/osteonecrosis (AVN) in 4598 children and young adults with glomerular disease were compared with those among 553,624 general pediatric patients using Poisson regression analysis. The glomerular disease cohort was identified using a published computable phenotype. Inclusion criteria for the general pediatric cohort were two or more primary care visits 1 year or more apart between 1 and 21 years of age, one visit or more every 18 months if followed3 years, and no chronic progressive conditions defined by the Pediatric Medical Complexity Algorithm. Fracture, SCFE, and AVN were identified using SNOMED-CT diagnosis codes; fracture required an associated x-ray or splinting/casting procedure within 48 hours.We found a higher risk of fracture for the glomerular disease cohort compared with the general pediatric cohort in girls only (incidence rate ratio [IRR], 1.6; 95% CI, 1.3 to 1.9). Hip/femur and vertebral fracture risk were increased in the glomerular disease cohort: adjusted IRR was 2.2 (95% CI, 1.3 to 3.7) and 5 (95% CI, 3.2 to 7.6), respectively. For SCFE, the adjusted IRR was 3.4 (95% CI, 1.9 to 5.9). For AVN, the adjusted IRR was 56.2 (95% CI, 40.7 to 77.5).Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

BACKGROUND: Uromodulin regulates activity of the sodium-potassium-two-chloride transporter in the loop of Henle. In adults, higher urine uromodulin levels are associated with greater rise in blood pressure (BP) in response to salt intake. We hypothesized that higher urine uromodulin levels would be associated with higher BP in children with chronic kidney disease, and that there would be an interaction of dietary sodium on this association. METHODS: In the chronic kidney disease in children Cohort, we utilized univariable and multivariable linear regression models to evaluate the relationship between baseline spot urine uromodulin levels indexed to urine creatinine (Umod/Cr mg/g) and 24-hour mean systolic and diastolic BP, as well as baseline clinic BP. We also tested whether sodium intake (g/day) modified these relationships. RESULTS: Among 436 participants, the median age was 12.4 years (8.9–15.2), median estimated glomerular filtration rate was 50 mL/min per 1.73 m 2 (36–62), and median 24-hour mean systolic BP was 112 mm Hg (104–119). The etiology of chronic kidney disease was glomerular disease in 27%. In univariable models, each 2-fold higher Umod/Cr ratio was associated with a 1.66 mm Hg (95% CI, −2.31 to −1.00) lower 24-hour mean systolic and a 1.71 mm Hg (−2.45 to −0.97) lower clinic systolic BP. However, there was no statistically significant association between Umod/Cr and either 24-hour or clinic BP in multivariable models. We did not find a significant interaction between uromodulin and sodium intake in their effect on BP ( P >0.05 in all models). CONCLUSIONS: Urine uromodulin levels are not associated with BP in the chronic kidney disease in children cohort. Further studies are needed to confirm this finding in healthy pediatric cohorts.

Background: Ambulatory blood pressure monitoring (ABPM) is routinely performed in children with chronic kidney disease to identify masked hypertension, a risk factor for accelerated chronic kidney disease progression. However, ABPM is burdensome, and developing an accurate prediction of masked hypertension may allow using ABPM selectively rather than routinely. Methods: To create a prediction model for masked hypertension using clinic blood pressure (BP) and other clinical characteristics, we analyzed 809 ABPM studies with nonhypertensive clinic BP among the participants of the Chronic Kidney Disease in Children study. Results: Masked hypertension was identified in 170 (21.0%) observations. We created prediction models for masked hypertension via gradient boosting, random forests, and logistic regression using 109 candidate predictors and evaluated its performance using bootstrap validation. The models showed C statistics from 0.660 (95% CI, 0.595–0.707) to 0.732 (95% CI, 0.695–0.786) and Brier scores from 0.148 (95% CI, 0.141–0.154) to 0.167 (95% CI, 0.152–0.183). Using the possible thresholds identified from this model, we stratified the dataset by clinic systolic/diastolic BP percentiles. The prevalence of masked hypertension was the lowest (4.8%) when clinic systolic/diastolic BP were both Conclusions: ABPM could be used selectively in those with low clinic BP, for example, systolic BP

To examine the relationship between neighborhood poverty and deprivation, chronic kidney disease (CKD) comorbidities, and disease progression in children with CKD.Observational cohort study.Children with mild to moderate CKD enrolled in the CKiD (Chronic Kidney Disease in Children) study with available US Census data.Neighborhood poverty and neighborhood disadvantage.Binary outcomes of short stature, obesity, hypertension, and health care utilization for cross-sectional analysis; a CKD progression end point (incident kidney replacement therapy [KRT] or 50% loss in estimated glomerular filtration rate), and mode of first KRT for time-to-event analysis.Cross-sectional analysis of health characteristics at time of first Census data collection using logistic regression to estimate odds ratios. Risk for CKD progression was analyzed using a Cox proportional hazard model. Multivariable models were adjusted for race, ethnicity, sex, and family income.There was strong agreement between family and neighborhood socioeconomic characteristics. Risk for short stature, hospitalization, and emergency department (ED) use were significantly associated with lower neighborhood income. After controlling for race, ethnicity, sex, and family income, the odds of hospitalization (OR, 1.71 [95% CI, 1.08-2.71]) and ED use (OR, 1.56 [95% CI, 1.02-2.40]) remained higher for those with lower neighborhood income. The hazard ratio of reaching the CKD progression outcome for participants living in lower income neighborhoods was significantly increased in the unadjusted model only (1.38 [95% CI, 1.02-1.87]). Likelihood of undergoing a preemptive transplant was decreased with lower neighborhood income (OR, 0.47 [95% CI, 0.24-0.96]) and higher neighborhood deprivation (OR, 0.31 [95% CI, 0.10-0.97]), but these associations did not persist after controlling for participant characteristics.Limited generalizability, as only those with consistent longitudinal nephrology care were studied.Neighborhood-level socioeconomic status (SES) was associated with poorer health characteristics and CKD progression in univariable analysis. However, the relationships were attenuated after accounting for participant-level factors including race. A persistent association of neighborhood poverty with hospitalizations and ED suggests an independent effect of SES on health care utilization, the causes for which deserve additional study.

BACKGROUND AND OBJECTIVES: Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (n=350) and noncases (n=350). RESULTS: Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months. CONCLUSIONS: Electronic health record–based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.

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

Diastolic dysfunction is one of the earliest cardiac abnormalities in patients with chronic kidney disease. We analyzed echocardiographic markers of left ventricular function from 786 children and adolescents (1658 person-visits) enrolled in the CKiD (Chronic Kidney Disease in Children) cohort, a large prospective observational study of children with chronic kidney disease. Primary outcome was early mitral inflow velocity-to-early mitral annular peak velocity (E/e′) ratio as a marker of left ventricular compliance. Abnormal diastolic function was defined as E/e′>8.0. Those with an abnormal E/e′ ratio were younger, had a lower estimated glomerular filtration rate and hemoglobin, and a higher prevalence of hypertension and left ventricular hypertrophy compared to children with a normal E/e′. In adjusted analysis, a higher E/e′ ratio was independently associated with ambulatory (sustained) hypertension (1.66 [95% CI, 1.15–2.42]). Other significant independent predictors were higher left ventricular mass index Z score, increased body mass index Z score, lower hemoglobin, higher phosphorus level, and younger age. Casual blood pressure was not significantly associated with higher E/e′. These data indicate that ambulatory blood pressure might better identify children with chronic kidney disease at risk for subclinical cardiac dysfunction than clinic blood pressure alone. Graphic Abstract: An online graphic abstract is available for this article.

An increasing amount of literature has indicated that chronic kidney disease (CKD) is associated with cognitive deficits that increase with worsening disease severity. Although abnormalities in brain structure have been widely documented, few studies to date have examined the functioning of brain areas associated with the specific cognitive domains affected by CKD (namely, attention and executive functions). Furthermore, few studies have examined functional connectivity among CKD youth who are relatively early in the course of the disease. The present study used functional magnetic resonance imaging to examine the resting state connectivity in 67 youth with CKD (mean age, 17 y) and 58 age-matched healthy controls. Using seed-based multiple regression, decreased connectivity was observed within the anterior cingulate portion of the default mode network. In addition, decreased connectivity within the dorsolateral prefrontal cortex, paracingulate gyrus, and frontal pole were correlated significantly with disease severity. These data indicate that connectivity deficits in circuits implementing attentional processes may represent an early marker for cognitive decline in CKD.

Heritable connective tissue disorders are a group of diseases, each rare, characterized by various combinations of skin, joint, musculoskeletal, organ, and vascular involvement. Although kidney abnormalities have been reported in some connective tissue disorders, they are rarely a presenting feature. Here we present three patients with prominent kidney phenotypes who were found by whole exome sequencing to have variants in established connective tissue genes associated with Loeys-Dietz syndrome and congenital contractural arachnodactyly. These cases highlight the importance of considering connective tissue disease in children presenting with structural kidney disease and also serves to expand the phenotype of Loeys-Dietz syndrome and possibly congenital contractural arachnodactyly to include cystic kidney disease and cystic kidney dysplasia, respectively.

Rationale & objective To identify differences in socioeconomic factors (SES) and subclinical CVD markers by race among CKiD participants and determine whether differences in CVD markers persist after adjusting for SES. Study design Analysis of 3103 visits with repeated measures from 628 children (497 Caucasian; 131 African American) enrolled in the CKiD study. Setting & participants Children with mild-moderate CKD with at least 1 CV parameter (ambulatory blood pressure, left ventricular mass index [LVMI], or lipid profile) measured. Exposures African American race OUTCOMES: Ambulatory hypertension, LVMI, triglycerides, high-density lipoprotein-cholesterol. Analytical approach Due to increased CV risks of glomerular disease, the analysis was stratified by CKD etiology. Inverse probability weighting was used to adjust for SES (health insurance, household income, maternal education, food insecurity, abnormal birth history). Linear and logistic regression were used to evaluate association of race with CV markers. Results African American children were disproportionately affected by adverse SES. African Americans with non-glomerular CKD had more ambulatory hypertension and higher LVMI, but more favorable lipid profile; after adjustment for SES, age, and sex, the magnitude of differences in these CV markers attenuated but remained statistically significant. Only LVMI differed by race in the glomerular CKD group, despite adjustment for SES. Limitations Study design limits causal inference. Conclusion African American children with CKD are disproportionately affected by socioeconomic disadvantages compared with Caucasians. The degree to which CV markers differ by race is influenced by disease etiology. African Americans with non-glomerular CKD have increased LVMI, more ambulatory hypertension and favorable lipid profile, but a trend towards attenuation in magnitude after adjustment for SES was observed. African Americans with glomerular CKD have increased LVMI, which persisted after SES adjustment. As many social determinants of health were not captured, future research should examine effects of systemic racism on CV health in this population.

Background More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care. Methods Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology—Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8–21 years) and caregivers (of children ages 0–21 years) pertaining to blood pressure. Results Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects). Conclusions For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD.

Accurate detection of hypertension is crucial for clinical management of pediatric chronic kidney disease (CKD). The 2017 American Academy of Pediatrics childhood hypertension guidelines included new normative blood pressure (BP) values and revised definitions of BP categories. In this study, we examined the effect of applying these changes to the Chronic Kidney Disease in Children (CKiD) cohort compared to use of the 2004 Fourth Report normative data and definitions.Observational cohort study.Children and adolescents in the CKiD cohort.Clinic blood pressure measurements.Blood pressure percentiles and hypertension stages calculated using the 2017 and 2004 guidelines.Agreement analysis compared the estimated percentile and prevalence of high blood pressure based on the 2017 and 2004 guidelines to clinic and combined ambulatory blood pressure readings.The proportion of children classified as having normal clinic blood pressure was similar using the 2017 and 2004 guidelines, but the use of the 2017 normative data classified more participants as having hypertensive-range blood pressure (22% vs. 11%) with marginal reproducibility (kappa= 0.569, 95%CI: 0.538, 0.599). Those identified as hypertensive by the 2017 guidelines had higher levels of proteinuria compared to those identified using the 2004 guidelines. There were substantially more participants with white coat and ambulatory hypertension when using the 2017 guidelines (3.5% vs. 1.5%; and 15.5% vs. 7.9%, respectively). The proportion with masked hypertension was lower using the 2017 guidelines (40.2% vs. 47.8%, respectively) with good reproducibility (kappa= 0.799, 95%CI: 0.778, 0.819), and the percentage of participants with normal ambulatory blood pressure was similar (40.9% vs. 42.9%, respectively), LIMITATIONS: Relationship with long-term progression and target organ damage was not assessed.A greater percentage of children with CKD were identified as hypertensive based on both clinic and ambulatory blood pressure when using the 2017 vs. the 2004 guidelines, and the 2017 guidelines better discriminated those with higher levels of proteinuria. The substantial differences in the classification of hypertension when using the 2004 vs. 2017 guidelines should inform clinical care.

BACKGROUND: Chronic kidney disease (CKD) is associated with many comorbidities requiring complex management. We described treatment patterns for common modifiable CKD complications (high blood pressure, anemia, hyperphosphatemia, and acidosis) according to severity of CKD and examined factors associated with the absence of drug therapy, among participants with a persistent comorbidity, for 1 year in children enrolled in the CKiD study. METHODS: A total of 703 CKiD participants contributed 2849 person-visits over a median 3.5 years of follow-up. Using pairs of annual visits, we examined whether participants with abnormal biomarker levels at the first (index) visit persisted in the abnormal levels 1 year later according to CKD risk stage. Multivariate analyses identified demographic and clinical factors associated with the absence of drug therapy among those with persistent comorbid conditions for 1 year. RESULTS: The overall proportions of person-visits prescribing therapy at 1-year follow-up for treating anemia, acidosis, hyperphosphatemia, and high blood pressure were 54%, 45%, 29%, and 81%, respectively. The frequency of therapy increased with advanced CKD risk stage for all comorbidities; however, 19–23% of participants with acidosis, 24–27% with anemia, and 30–39% with hyperphosphatemia at high-risk stages (E and F) were not prescribed appropriate therapy despite the persistence of abnormal levels of these biomarkers for at least 1 year. The resolution of comorbidities at advanced CKD stages without treatment was unlikely. CONCLUSIONS: Many children with CKD in the CKiD cohort did not receive pharmacological treatment for common and persistent modifiable comorbidities, even in severe CKD risk stages.

Background Pediatric research is a diverse field that is constantly growing. Current machine learning advancements have prompted a technique termed text-mining. In text-mining, information is extracted from texts using algorithms. This technique can be applied to analyze trends and to investigate the dynamics in a research field. We aimed to use text-mining to provide a high-level analysis of pediatric literature over the past two decades. Methods We retrieved all available MEDLINE/PubMed annual data sets until December 31, 2018. Included studies were categorized into topics using text-mining. Results Two hundred and twenty-five journals were categorized as Pediatrics, Perinatology, and Child Health based on Scimago ranking for medicine journals. We included 201,141 pediatric papers published between 1999 and 2018. The most frequently cited publications were clinical guidelines and meta-analyses. We found that there is a shift in the trend of topics. Epidemiological studies are gaining more publications while other topics are relatively decreasing. Conclusions The topics in pediatric literature have shifted in the past two decades, reflecting changing trends in the field. Text-mining enables analysis of trends in publications and can serve as a high-level academic tool. Impact Text-mining enables analysis of trends in publications and can serve as a high-level academic tool. This is the first study using text-mining techniques to analyze pediatric publications. Our findings indicate that text-mining techniques enable better understanding of trends in publications and should be implemented when analyzing research.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided.

To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD). Retrospective longitudinal cohort study in infants admitted to United States children’s hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use. We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy. Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.

Normally, blood pressure (BP) declines by at least 10% from daytime to nighttime. In adults, blunted nocturnal dipping has been associated with more rapid decline in kidney function. Nondipping is prevalent in children with chronic kidney disease (CKD). We sought to determine whether nondipping is associated with proteinuria and progression to kidney failure in children with CKD.In the prospective CKD in children (CKiD) cohort, Cox proportional hazards models were used to evaluate the relationship between baseline nondipping and progression to kidney failure. Linear mixed effects models were used to evaluate the relationship between nondipping and changes in iohexol glomerular filtration rate (GFR) and urine protein-to-creatinine ratio (log-UPCR, mg/mg) over time.Among 620 participants, mean age was 11 (± 4) years, mean iohexol GFR was 52 (± 22) ml/min per 1.73 mNondipping is not associated with end-stage kidney disease, GFR decline, or change in proteinuria within the CKiD cohort.

To understand the association between health and dental insurance status and health and dental care utilization, and their relationship with disease severity in a population with childhood-onset chronic kidney disease (CKD).Observational cohort study.Nine hundred fifty-three participants contributing 4,369 person-visits (unit of analysis) in the United States enrolled in the Chronic Kidney Disease in Children (CKiD) Study from 2005 to 2019.Health insurance (private vs public vs none) and dental insurance (presence vs absence) self-reported at annual visits.Self-reported suboptimal health care utilization in the past year, defined separately as not visiting a private physician, visiting the emergency room, visiting the emergency room at least twice, being hospitalized, and self-reported suboptimal dental care utilization over the past year, defined as not receiving dental care.Repeated measures Poisson regression models were fit to estimate and compare utilization by insurance type and disease severity at the prior visit. Additional unadjusted and adjusted models were fit, as well as models including interactions between insurance and Black race, maternal education, and income.Those with public health insurance were more likely to report suboptimal health care utilization across the CKD severity spectrum, and lack of dental insurance was strongly associated with lack of dental care. These relationships varied depending on strata of socioeconomic status and race but the effect measure modification was not significant.Details of insurance coverage were unavailable; reasons for emergency care or type of private physician visited were unknown.Pediatric nephrology programs may consider interventions to help direct supportive resources to families with public insurance who are at higher risk for suboptimal utilization of care. Insurance providers should identify areas to expand access for families of children with CKD.

Anemia and statural growth impairment are both prevalent in children with non-glomerular chronic kidney disease (CKD) and are associated with poor quality of life, and increased morbidity and mortality. However, to date, no longitudinal studies have demonstrated a relationship between anemia and statural growth in this population.The CKD in Children (CKiD) study is a multicenter prospective cohort study with over 15 years of follow-up.CKiD participants less than 22 years of age with non-glomerular CKD who had not reached final adult height.Age-sex-race-specific hemoglobin z-score.Age-sex-specific height z-score.(1) Multivariable repeated measures paired person-visit analysis. (2) Multivariable repeated measures linear mixed model analysis. Both models were adjusted for age, sex, BMI, GFR, acidosis, and medication use.Overall, 67% of the 510 participants studied had declining hemoglobin z-score trajectories over follow-up that included 1763 person-visits. Compared to average hemoglobin z-scores0, average hemoglobin z-scores of-1.0 were independently associated with significant growth impairment at the subsequent study visit, with height z-score decline ranging from 0.24 to 0.35. Importantly, in 50% of cases, hemoglobin z-scores of-1.0 corresponded to hemoglobin values higher than those used as cutoffs defining anemia in the KDIGO guidelines. When stratified by age, the magnitude of the association peaked at 9 years. In line with paired-visit analyses, our mixed model analysis demonstrated that in participants with baseline hemoglobin z-score-1.0, hemoglobin z-score decline over follow-up was associated with a statistically significant concurrent decrease in height z-score.Limited ability to infer causality.Hemoglobin decline is associated with growth impairment over time in children with mild to moderate non-glomerular CKD, even before hemoglobin levels reach the cutoffs that are currently used to define anemia in this population.

BACKGROUND: Control of hypertension delays progression of pediatric chronic kidney disease (CKD), yet few data are available regarding what office blood pressure (BP) levels may slow progression. METHODS: Longitudinal BP data from children in the Chronic Kidney Disease in Children cohort study who had hypertension or an auscultatory BP ≥90th percentile enrolled were studied. BP categories were defined as the maximum systolic or diastolic BP percentile (

Studies in healthy children have shown racial-ethnic differences in bone markers and bone outcomes including fractures. At present, limited studies have evaluated the impact of race and ethnicity on bone markers and fractures within the pediatric chronic kidney disease (CKD) population. In a cohort study of 762 children between the ages of 1.5 years and 18 years, with CKD stages 1 to 4 from the CKD in children (CKiD) cohort, the relationship between racial-ethnic group and bone markers (parathyroid hormone [PTH], 25-hydroxyvitamin D [25-OHD], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and C-terminal fibroblast growth factor [FGF23]) was determined using linear mixed models. Additionally, logistic regression was used to evaluate racial-ethnic differences in prevalent fracture upon study entry. Black race was associated with 23% higher PTH levels (confidence interval [CI], 2.5% to 47.7%; p = .03), 33.1% lower 25-OHD levels (CI, -39.7% to -25.7%; p < .0001), and no difference in C-terminal FGF23 or 1,25(OH)2 D levels when compared to whites. Hispanic ethnicity was associated with 15.9% lower C-terminal FGF23 levels (CI, -28.3% to -1.5%; p = .03) and 13.8% lower 25-OHD levels (CI, -22.2% to -4.5%; p = .005) when compared to whites. Black and Hispanic children had 74% (odds ratio [OR] 0.26; CI, 0.14 to 0.49; p = .001) and 66% (OR 0.34; CI, 0.17 to 0.65; p < .0001) lower odds of any fracture than white children at study entry, respectively. Race and ethnicity are associated with differences in bone markers and despite lower 25-OHD levels, both black and Hispanic children with CKD reported a lower prevalent fracture history than white children. The current findings in the CKD population are similar to racial-ethnic differences described in healthy children. Additional studies are needed to better understand how these differences might impact the management of pediatric CKD-MBD. © 2020 American Society for Bone and Mineral Research (ASBMR).

BACKGROUND The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early-stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI). METHODS The sample age range was 6-16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1-3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status. RESULTS Cerebellar gray matter volume was significantly smaller in pCKD, t(38) = -2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38) = 2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14) = 2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment. CONCLUSIONS This study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD. IMPACT The impact of pediatric chronic kidney disease (CKD) on the brain remains poorly defined, with no data linking brain morphometry and observed cognitive deficits noted in this population. We explored the relationship between brain morphometry (using structural magnetic resonance imaging), cognition, and markers of CKD. Cerebellar and cerebral gray matter volumes are different in early CKD. Volumetric decreases in cerebellar gray matter are predicted by lower eGFR, suggesting a link between disease and brain morphometry. Reduced cerebellar gray matter predicted lower verbal fluency for those with pCKD. Enlarged cerebral gray matter in the pCKD sample predicted lower mathematics performance.

OBJECTIVES: To evaluate whether liver and spleen magnetic resonance elastography (MRE) can measure the severity of congenital hepatic fibrosis (CHF) and portal hypertension (pHTN) in individuals with autosomal recessive polycystic kidney disease (ARPKD), and to examine correlations between liver MRE and ultrasound (US) elastography. METHODS: Cross-sectional study of 9 individuals with ARPKD and 14 healthy controls. MRE was performed to measure mean liver and spleen stiffness (kPa); US elastography was performed to measure point shear wave speed (SWS) in both liver lobes. We compared: (1) MRE liver and spleen stiffness between controls vs. ARPKD; and (2) MRE liver stiffness between participants with ARPKD without vs. with pHTN, and examined correlations between MRE liver stiffness, spleen length, platelet counts, and US elastography SWS. Receiver operating characteristic (ROC) analysis was performed to examine diagnostic accuracy of liver MRE. RESULTS: Participants with ARPKD (median age 16.8 [IQR 13.3, 18.9] years) had higher median MRE liver stiffness than controls (median age 14.7 [IQR 9.7, 16.7 years) (2.55 vs. 1.92 kPa, p=0.008), but MRE spleen stiffness did not differ. ARPKD participants with pHTN had higher median MRE liver stiffness than those without (3.60 kPa vs 2.49 kPa, p=0.05). Liver MRE and US elastography measurements were strongly correlated. To distinguish ARPKD vs. control groups, liver MRE had 78% sensitivity and 93% specificity at a proposed cut-off of 2.48 kPa [ROC area 0.83 (95% CI: 0.63–1.00)]. CONCLUSION: Liver MRE may be a useful quantitative method to measure the severity of CHF and pHTN in individuals with ARPKD.

OBJECTIVE To reliably and quickly diagnose children with posterior urethral valves (PUV), we developed a multi-instance deep learning method to automate image analysis. METHODS We built a robust pattern classifier to distinguish 86 children with PUV from 71 children with mild unilateral hydronephrosis based on ultrasound images (3504 in sagittal view and 2558 in transverse view) obtained during routine clinical care. RESULTS The multi-instance deep learning classifier performed better than classifiers built on either single sagittal images or single transverse images. Particularly, the deep learning classifiers built on single images in the sagittal view and single images in the transverse view obtained area under the receiver operating characteristic curve (AUC) values of 0.796 ± 0.064 and 0.815 ± 0.071, respectively. AUC values of the multi-instance deep learning classifiers built on images in the sagittal and transverse views with mean pooling operation were 0.949 ± 0.035 and 0.954 ± 0.033, respectively. The multi-instance deep learning classifiers built on images in both the sagittal and transverse views with a mean pooling operation obtained an AUC of 0.961 ± 0.026 with a classification rate of 0.925 ± 0.060, specificity of 0.986 ± 0.032, and sensitivity of 0.873 ± 0.120, respectively. Discriminative regions of the kidney located using classification activation mapping demonstrated that the deep learning techniques could identify meaningful anatomical features from ultrasound images. CONCLUSION The multi-instance deep learning method provides an automatic and accurate means to extract informative features from ultrasound images and discriminate infants with PUV from male children with unilateral hydronephrosis.

Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. “Cases” were defined as individuals receiving any kidney replacement therapy (KRT), while “controls” were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0–13.0) and 15.9 (13.9–16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.

BACKGROUND: Preparing children with chronic kidney disease (CKD) for renal replacement therapy (RRT) begins with a discussion about transplant and dialysis, but its typical timing in the course of CKD management is unclear. We aimed to describe participant-reported RRT planning discussions by CKD stage, clinical and sociodemographic characteristics, in the Chronic Kidney Disease in Children (CKiD) cohort. METHODS: Participants responded to the question “In the past year, have you discussed renal replacement therapy with your doctor or health care provider?” at annual study visits. Responses were linked to the previous year CKD risk stage based on GFR and proteinuria. Repeated measures logistic models estimated the proportion discussing RRT by stage, with modification by sex, age, race, socioeconomic status and CKD diagnosis (glomerular vs. non-glomerular). RESULTS: 721 CKiD participants (median age= 12, 62% boys) contributed 2856 person-visits. Proportions of person-visits reporting RRT discussions increased as CKD severity increased (10% at the lowest disease stage and 87% at the highest disease stage). After controlling for CKD risk stage, rates of RRT discussions did not differ by sex, age, race and socioeconomic status. CONCLUSIONS: Despite participant-reported RRT discussions being strongly associated with CKD severity, a substantial proportion with advanced CKD reported no discussion. While recall bias may lead to underreporting, it is still meaningful that some participants with severe CKD did not report or remember discussing RRT. Initiating RRT discussions early in the CKD course should be encouraged to foster comprehensive preparation and to align RRT selection for optimal health and patient preferences.

Children with chronic kidney disease (CKD) have delays in normal growth and pubertal development. We describe factors associated with delayed menarche and the association of delayed menarche with short stature in girls with CKD. Two hundred eighty-seven girls with CKD onset prior to menarche within the Chronic Kidney Disease in Children (CKiD) cohort were studied. Delayed menarche was defined as menarche at age 15 years or older; short stature was defined as last available height 2 standard deviations below projected adult height. Kaplan-Meier cumulative incidence function was used to estimate median age at menarche. Chi-squared and Wilcoxon rank-sum tests were used to assess factors associated with delayed menarche. Chi-squared test was used to evaluate the association between delayed menarche and short stature. Among 287 girls, 68 enrolled with prevalent menarche, 131 were observed to have incident menarche, and 88 were pre-menarchal at their last study visit. Median age at menarche was 12 years. Ten percent had delayed menarche. African American race, lower estimated glomerular filtration rate, ever corticosteroid use, and longer CKD duration were associated with delayed menarche (p

BACKGROUND: To evaluate impact of anemia on health-related quality of life (HRQOL) over time in a large pediatric cohort with mild-to-moderate chronic kidney disease (CKD). METHODS: Participants were enrolled in the Chronic Kidney Disease in Children Study (CKiD), a multicenter, longitudinal cohort. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL). Anemia was defined as hemoglobin < 5th percentile for age, sex, and race. Two longitudinal analyses were conducted on consecutive visit pairs. Models examined effects of anemia status on both HRQOL score over time and change in HRQOL score between consecutive visits. The sample included 733 children with a median estimated GFR 54 ml/min/1.73 m(2). Thirty percent of children had anemia at index visit. RESULTS: Analysis of HRQOL scores revealed the presence of anemia was associated with significantly lower overall HRQOL (β = −2.90 (95% CI = −7.74, −0.21), p = 0.04) and physical functioning (β = −5.72 (−9.49, −2.25), p = 0.001) according to children. On parent ratings, the development of anemia was associated with lower emotional functioning scores (β = −4.87 (−8.72, −0.11), p = 0.045). In the second model, children who developed anemia were rated by caregivers as having more decreased physical functioning than children who remained anemia-free (β = −3.30 per year (−5.83, −0.76), p = 0.01). Caregivers did not observe declines in their children’s other PedsQL subscales in the presence of developed anemia. Children with resolved or persistence did not show improvement or decline in any aspect of HRQOL functioning relative to non-anemic subjects. CONCLUSIONS: In children with CKD, anemia has an adverse effect on HRQOL which persists over time but does not appear to be progressive.

BACKGROUND AND OBJECTIVES: In adult chronic kidney disease (CKD), metabolic acidosis is associated with diminished cognition, notably executive function (EF). Data from the Chronic Kidney Disease in Children (CKiD) study demonstrate a risk for impairment of EF, a finding associated with heightened blood pressure variability (BPV). We sought to determine whether low serum bicarbonate is also associated with performance on tests of EF in pediatric CKD and to investigate potential interaction with BPV. DESIGN/METHODS: CKiD participants with serum bicarbonate, blood pressure, and selected cognitive measurements available were evaluated. An EF summary score was derived from scores on the Delis Kaplan Executive Function System, Conners’ Continuous Performance Test, and Digit Span Backwards subtest from the Wechsler Intelligence Scale for Children-IV-Integrated. Parents completed the Behavioral Rating Inventory of Executive Function (BRIEF) to yield a Global Executive Composite (GEC) score. Linear mixed models with bicarbonate and hypertension as predictors and linear regression with bicarbonate and BPV were used to predict EF level. RESULTS: Data were available for 865 children. Twenty-two percent had low bicarbonate (CO(2) ≤ 20 mmol/L) at baseline. On multivariate analysis, there was no relationship between bicarbonate, hypertension, and EF. There was no significant CO(2)×hypertension interaction found. A significant interaction (p= 0.01) between high CO(2) (≥ 26 mmol/L) and BPV was detected in the model with GEC as the EF outcome, indicating that while higher BPV was associated with worse EF in the low and normal CO(2) groups, higher BPV was associated with better EF in the high CO(2) group. CONCLUSIONS: Our analyses revealed an interaction between one measure of BPV and low bicarbonate on neurocognition in pediatric CKD, suggesting a potential role for control of both bicarbonate and blood pressure in preserving cognition in early CKD. Further research is needed to confirm and further define this association.

BACKGROUND: This study aimed to determine stroke incidence and assess the association between stroke and neurocognitive functioning in children with chronic kidney disease (CKD). METHODS: Data was derived from the Chronic Kidney Disease in Children (CKiD) cohort study. Stroke incidence was calculated after confirming self-reports of stroke occurrence by chart review. Each participant with stroke was matched with three stroke-free participants and performance on selected neurocognitive measures was compared. Wilcoxon rank-sum tests were used to compare neurocognitive test scores. Effect size (ES) was estimated using a modified version of Cohen’s U(3) metric that measures the excess percentage of the stroke group worse than the median of the control group. RESULTS: Of 891 subjects, five (0.56%) had a confirmed stroke prior to study entry. Median time at risk was 15.7 years [interquartile range, 12.5–18.4]. Estimated incidence rate of history of stroke was 36.8 per 100,000 children per year (95% confidence interval 15.3, 88.5). Controls and subjects with stroke were similar in age, CKD duration, race, and maternal education. ES for many of the neurocognitive comparisons was moderate to large. Subjects in the CKID cohort with a history of stroke had lower scores on spatial span reverse, spatial span forward, and design fluency, and worse parent ratings on BRIEF Metacognition Index compared to a matched sample of children with CKD without stroke. CONCLUSIONS: Children with CKD have an increased incidence of prior ischemic stroke compared to the general pediatric population. A stroke history was associated with poorer performance on neurocognitive measures.

The Chronic Kidney Disease in Children (CKiD) cohort study is a North American (USA and Canada) multicenter, prospective study of children with chronic kidney disease (CKD). The original aims of the study were (1) to identify novel risk factors for CKD progression; (2) to measure the impact of kidney function decline on growth, cognition, and behavior; and (3) to characterize the evolution of cardiovascular disease risk factors. CKiD has developed into a national and international resource for the investigation of a variety of factors related to CKD in children. This review highlights notable findings in the area of CKD progression and outlines ongoing opportunities to enhance understanding of CKD progression in children. CKiD's contributions to the clinical care of children with CKD include updated and more accurate glomerular filtration rate estimating equations for children and young adults, and resources designed to help estimate the CKD progression timeline. In addition, results from CKiD have strengthened the evidence that treatment of hypertension and proteinuria should continue as a primary strategy for slowing the rate of disease progression in children.

Children with mild to moderate chronic kidney disease are at an increased risk for cardiovascular sequelae, the leading cause of death in children with end-stage renal disease. We aimed to establish the prevalence of aortic dilatation, a newly recognized cardiovascular sequelae of renal disease, within a cohort of pediatric patients with mild to moderate kidney disease. A total of 501 children enrolled in the Chronic Kidney Disease in Children study contributed imaging data between April 2011 and February 2015. Aortic dilatation was defined as a dimension exceeding a z-score of 2 at any of three locations: aortic root, sinotubular junction, or the ascending aorta. At baseline echocardiographic evaluation, 30 (6%) children were identified to have aortic dilatation in at least one of the three locations. Multivariate analysis demonstrated an increased odds ratio for the presence of aortic dilatation associated with the following variables: high diastolic blood pressure z-scores, low weight z-score, and low body mass index z-score. Presense of protein energy wasting (modified definition, OR 2.41, 95%CI 1.23, 4.70) was the strongest independent predictor of aortic dilatation. In conclusion, aortic dilatation does occur early in the course of chronic kidney disease and associates with markers of poor nutrition. Future studies should continue to evaluate these risk factors longitudinally as the kidney disease progresses.

Background Adolescents with chronic kidney disease (CKD) are a unique population with a high prevalence of hypertension. Management of hypertension during the transition from adolescence to adulthood can be challenging given differences in normative blood pressure values in adolescents compared with adults. Methods In this retrospective analysis of the Chronic Kidney Disease in Children Cohort Study, we compared pediatric versus adult definitions of ambulatory- and clinic-diagnosed hypertension in their ability to discriminate risk for left ventricular hypertrophy (LVH) and kidney failure using logistic and Cox models, respectively. Results Overall, among 363 adolescents included for study, the prevalence of systolic hypertension was 27%, 44%, 12%, and 9% based on pediatric ambulatory, adult ambulatory, pediatric clinic, and adult clinic definitions, respectively. All definitions of hypertension were statistically significantly associated with LVH except for the adult ambulatory definition. Presence of ambulatory hypertension was associated with 2.6 times higher odds of LVH using pediatric definitions (95% CI 1.4–5.1) compared to 1.4 times higher odds using adult definitions (95% CI 0.8–3.0). The c-statistics for discrimination of LVH was statistically significantly higher for the pediatric definition of ambulatory hypertension (c=0.61) compared to the adult ambulatory definition (c=0.54), and the Akaike Information Criterion was lower for the pediatric definition. All definitions were associated with progression to kidney failure. Conclusion Overall, there was not a substantial difference in pediatric versus adult definitions of hypertension in predicting kidney outcomes, but there was slightly better risk discrimination of the risk of LVH with the pediatric definition of ambulatory hypertension. Graphical abstract

Background BK polyomavirus (BKPyV) is associated with symptomatic hemorrhagic cystitis after hematopoietic cell transplantation (HCT). Little is known about the host immune response, effectiveness of antiviral treatment, or impact of asymptomatic replication on long-term kidney function. Methods In children and young adults undergoing allogeneic HCT, we quantified BKPyV viruria and viremia (pre-HCT and at Months 1–4, 8, 12, and 24 post-HCT) and tested associations of peak viremia ≥10 000 or viruria ≥109 copies/mL with estimated kidney function (glomerular filtration rate, eGFR) and overall survival at 2 years posttransplant. We examined the factors associated with viral clearance by Month 4, including BKPyV-specific T cells by enzyme-linked immune absorbent spot at Month 3 and cidofovir use. Results We prospectively enrolled 193 participants (median age 10 years) and found that 18% had viremia ≥10 000 copies/mL and 45% had viruria ≥109 copies/mL in the first 3 months post-HCT. Among the 147 participants without cystitis (asymptomatic), 58 (40%) had any viremia. In the entire cohort and asymptomatic subset, having viremia ≥10 000 copies/mL was associated with a lower creatinine/cystatin C eGFR at 2 years post-HCT. Viremia ≥10 000 copies/mL was associated with a higher risk of death (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1–4.2). Clearing viremia was associated with detectable BKPyV-specific T cells and having viremia Conclusions Screening for BKPyV viremia after HCT identifies asymptomatic patients at risk for kidney disease and reduced survival. These data suggest potential changes to clinical practice, including prospective monitoring for BKPyV viremia to test virus-specific T cells to prevent or treat BKPyV replication.

Obesity is prevalent among children with chronic kidney disease (CKD) and is associated with cardiovascular disease and reduced quality of life. Its relationship with pediatric CKD progression has not been described.We evaluated relationships between both body mass index (BMI) category (normal, overweight, obese) and BMI z-score (BMIz) change on CKD progression among participants of the Chronic Kidney Disease in Children study. Kaplan-Meier survival curves and multivariable parametric failure time models depict the association of baseline BMI category on time to kidney replacement therapy (KRT). Additionally, the annualized percentage change in estimated glomerular filtration rate (eGFR) was modeled against concurrent change in BMIz using multivariable linear regression with generalized estimating equations which allowed for quantification of the effect of BMIz change on annualized eGFR change.Participants had median age of 10.9 years [IQR: 6.5, 14.6], median eGFR of 50 ml/1.73 mObesity may represent a target of intervention to improve kidney function in children with non-glomerular CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Autosomal recessive polycystic kidney disease (ARPKD) causes fibrocystic kidney disease, congenital hepatic fibrosis, and portal hypertension. Serum galectin-3 (Gal-3) and intestinal fatty acid binding protein (I-FABP) are potential biomarkers of kidney fibrosis and portal hypertension, respectively. We examined whether serum Gal-3 associates with kidney disease severity and serum I-FABP associates with liver disease severity in ARPKD.Cross-sectional study of 29 participants with ARPKD (0.2-21 years old) and presence of native kidneys (Gal-3 analyses, n = 18) and/or native livers (I-FABP analyses, n = 21). Serum Gal-3 and I-FABP were analyzed using enzyme linked immunosorbent assay. Kidney disease severity variables included estimated glomerular filtration rate (eGFR) and height-adjusted total kidney volume (htTKV). Liver disease severity was characterized using ultrasound elastography to measure liver fibrosis, and spleen length and platelet count as markers of portal hypertension. Simple and multivariable linear regression examined associations between Gal-3 and kidney disease severity (adjusted for liver disease severity) and between I-FABP and liver disease severity (adjusted for eGFR).Serum Gal-3 was negatively associated with eGFR; 1 standard deviation (SD) lower eGFR was associated with 0.795 SD higher Gal-3 level (95% CI - 1.116, - 0.473; p 0.001). This association remained significant when adjusted for liver disease severity. Serum Gal-3 was not associated with htTKV in adjusted analyses. Overall I-FABP levels were elevated, but there were no linear associations between I-FABP and liver disease severity in unadjusted or adjusted models.Serum Gal-3 is associated with eGFR in ARPKD, suggesting its value as a possible novel biomarker of kidney disease severity. We found no associations between serum I-FABP and ARPKD liver disease severity despite overall elevated I-FABP levels.

Study Objectives Obstructive sleep apnea is associated with neurobehavioral dysfunction, but the relationship between disease severity as measured by the apnea-hypopnea index and neurobehavioral morbidity is unclear. The objective of our study is to compare the neurobehavioral morbidity of mild sleep-disordered breathing versus obstructive sleep apnea. Methods Children 3–12 years old recruited for mild sleep-disordered breathing (snoring with obstructive apnea-hypopnea index < 3) into the Pediatric Adenotonsillectomy Trial for Snoring were compared to children 5–9 years old recruited for obstructive sleep apnea (obstructive apnea-hypopnea 2–30) into the Childhood Adenotonsillectomy Trial. Baseline demographic, polysomnographic, and neurobehavioral outcomes were compared using univariable and multivariable analysis. Results The sample included 453 participants with obstructive sleep apnea (median obstructive apnea-hypopnea index 5.7) and 459 participants with mild sleep-disordered breathing (median obstructive apnea-hypopnea index 0.5). By polysomnography, participants with obstructive sleep apnea had poorer sleep efficiency and more arousals. Children with mild sleep-disordered breathing had more abnormal executive function scores (adjusted odds ratio 1.96, 95% CI 1.30–2.94) compared to children with obstructive sleep apnea. There were also elevated Conners scores for inattention (adjusted odds ratio 3.16, CI 1.98–5.02) and hyperactivity (adjusted odds ratio 2.82, CI 1.83–4.34) in children recruited for mild sleep-disordered breathing. Conclusions Abnormal executive function, inattention, and hyperactivity were more common in symptomatic children recruited into a trial for mild sleep-disordered breathing compared to children recruited into a trial for obstructive sleep apnea. Young, snoring children with only minimally elevated apnea-hypopnea levels may still be at risk for deficits in executive function and attention. Trial Registration Pediatric Adenotonsillectomy for Snoring (PATS), NCT02562040; Childhood Adenotonsillectomy Trial (CHAT), NCT00560859

Introduction: In 2012, KDIGO released a guideline on BP management in CKD not receiving dialysis. The emergence of new trials and meta-analyses coupled with wider recognition of the importance of standardized BP measurement protocols have prompted a call to update the 2012 guideline. This summary will outline the changes to the prior recommendations and highlight similarities to guidelines from ACC/AHA and ESC/ESH. Methods: A systematic review was undertaken to formally assess the following issues: 1) BP measurement; 2) lifestyle interventions; BP management in 3) patients with CKD, with and without diabetes, 4) kidney transplant recipients, and 5) children with CKD. Results: A total of 6863 citations were screened. Of these, 290 RCTs, 14 observational studies, and 35 systematic reviews were included in the evidence review. A major addition to the KDIGO 2021 guideline is a chapter devoted to BP measurement. KDIGO recommends the use of standardized office BP over routine BP. Out-of-office measurements (ABPM, HBPM) can be used to complement standardized readings. This emphasis on standardized office BP measurement is similar to recommendations from ACC/AHA and ESC/ESH. A systolic BP target of Conclusions: KDIGO has revised its guideline for BP management in CKD based on a rigorous development process and emerging new evidence underscoring the importance of standardized office BP measurement and a lower systolic BP target of

Rationale & Objective: Clinical decision-making priorities may differ among children, their parents, and their clinicians. This study describes clinicians’ perspectives on shared decision making in pediatric chronic kidney disease (CKD) and identifies opportunities to improve shared decision making and care for children with CKD and their families. Study Design: Semistructured interviews. Setting & Participants: Fifty clinicians participated, including pediatric nephrologists, nurses, social workers, surgeons, dietitians, and psychologists involved in providing care to children with CKD. They worked at 18 hospitals and 4 university research departments across 11 countries (United States of America, Canada, Australia, People's Republic of China, United Kingdom, Germany, France, Italy, Lithuania, New Zealand, and Singapore). Analytical Approach: Interview transcripts were analyzed thematically. Results: We identified 4 themes: (1) striving to blend priorities (minimizing treatment burden, emphasizing clinical long-term risks, achieving common goals), (2) focusing on medical responsibilities (carrying decisional burden and pressure of expectations, working within system constraints, ensuring safety is foremost concern), (3) collaborating to achieve better long-term outcomes (individualizing care, creating partnerships, encouraging ownership and participation in shared decision making, sensitive to parental distress), and (4) forming cumulative knowledge (balancing reassurance and realistic expectations, building understanding around treatment, harnessing motivation for long-term goals). Limitations: Most clinicians were from high-income countries, so the transferability of the findings to other settings is uncertain. Conclusions: Clinicians reported striving to minimize treatment burden and working with children and their families to manage their expectations and support their decision making. However, they are challenged with system constraints and sometimes felt the pressure of being responsible for the child's long-term outcomes. Further studies are needed to test whether support for shared decision making would promote strategies to establish and improve the quality of care for children with CKD.

BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium. METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m(2) were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate). RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32–35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1). CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance.