Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses.

A hallmark of autoimmunity in murine models of lupus is the formation of germinal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate. In the host response to foreign antigens, follicular dendritic cells (FDCs) maintain GCs through the uptake and cycling of complement-opsonized immune complexes. Here, we examined whether FDCs retain self-antigens and the impact of this process in autoantibody secretion in lupus. We found that FDCs took up and retained self-immune complexes composed of ribonucleotide proteins, autoantibody, and complement. This uptake, mediated through CD21, triggered endosomal TLR7 and led to the secretion of interferon (IFN) α via an IRF5-dependent pathway. Blocking of FDC secretion of IFN-α restored B cell tolerance and reduced the amount of GCs and pathogenic autoantibody. Thus, FDCs are a critical source of the IFN-α driving autoimmunity in this lupus model. This pathway is conserved in humans, suggesting that it may be a viable therapeutic target in systemic lupus erythematosus.

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study.

OBJECTIVE: To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy. STUDY DESIGN: Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher's exact tests, and ANOVA. RESULTS: Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge. CONCLUSIONS: This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively.

What Level of Blood Pressure Is Concerning in Childhood?

The 95th percentile of blood pressure (BP) among healthy children is the currently accepted level used to denote a hypertensive BP reading in pediatric patients. Yet, ample data have emerged showing that the detrimental effects of high BP can be demonstrated at BP levels considered normal by current guidelines. Cardiac, vascular, cognitive, and kidney effects have been shown starting at the 90th percentile in cross-sectional studies, and markers of adult cardiovascular disease appear in longitudinal cohorts whose members had modestly elevated or even normal BP as youth. This review summarizes data that support a lower threshold of concern for children and adolescents, and outlines some of the remaining questions to be answered before a lower threshold BP level could be adopted.

The ongoing impact of obesity on childhood hypertension.

Obesity rates among children have been steadily rising over the past several decades. This epidemic has been accompanied by an increase in the prevalence of childhood hypertension, with children in low- and middle-income countries being affected to the same extent as children in high-income countries. This review will examine the trends in childhood blood pressure and the relationship between excess body weight and the development of hypertension. In addition, distinct mechanisms of obesity-related hypertension will be discussed. There will be an emphasis on recent studies conducted since the publication of new guidelines by the American Academy of Pediatrics in 2017 which resulted in the adoption of lower normative blood pressure cutoffs. The overall intent of this review is to provide the reader with an understanding of the ongoing impact, and complexities, of obesity-related hypertension.

Environmental exposure to melamine and its derivatives and kidney outcomes in children.

Melamine caused acute nephrotoxicity in a past food adulteration incident, but it is unclear whether and how widespread ambient exposure to melamine and related compounds might affect pediatric kidney health. We assessed cross-sectional associations between childhood exposure to melamine and its derivatives and biomarkers of kidney injury and health and explored potential heterogeneity by sex suggested by sex-dependent differences in renal physiology. We measured melamine and its derivatives ammeline, ammelide, and cyanuric acid (CYA) in spot urine samples collected from 192 children from an urban site (Seattle, WA) and 187 children from a rural site (Yakima, WA) aged 4-8 years in the Global Alliance to Prevent Prematurity and Stillbirth (GAPPS) Study. In addition, biomarkers of kidney injury were measured in the same urine samples, including albumin, total protein, KIM-1, NAG, NGAL, and EGF. We utilized linear regressions to examine associations between individual chemical exposures and kidney biomarkers. Interaction terms examined association modification by sex, as well as potential interactions between melamine and CYA. Despite comparable exposures, girls had higher levels of many kidney injury biomarkers compared to boys. A ten-fold higher melamine concentration was associated with a 18% (95% CI: 5.6%, 31%) higher EGF in the full sample, while ten-fold higher melamine was associated with a 76% (14.1%, 173%) higher KIM-1 in boys but not in girls (-10.1% (-40.6%, 36.1%), interaction p = 0.026). Melamine exhibited significant negative interactions with CYA in association with total protein and NAG that appeared to be specific to girls. Our results suggest possible associations between melamine exposure and markers of kidney injury that may be more pronounced in boys. These findings provide novel insights into melamine and related derivative compound health effects at low levels of exposure in children and emphasize the role of sex in mediating the relationship between nephrotoxicant exposure and kidney injury.

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

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

Improving Clinical Care for Children With CKD: A Report From a National Kidney Foundation Scientific Workshop.

Development of clinical guidelines and recommendations to address the care of pediatric patients with chronic kidney disease (CKD) has rarely included the perspectives of providers from a variety of health care disciplines or the patients and parents themselves. Accordingly, the National Kidney Foundation hosted an in-person, one and a half-day workshop that convened a multidisciplinary group of physicians, allied health care professionals, and pediatric patients with CKD 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 5 broad topics: addressing the needs of patients and parents/caregivers; modifying the progression of CKD; clinical management of CKD-mineral and 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.

Patient-Reported Outcomes Over 24 Months in Pediatric CKD: Findings From the MyKidneyHealth Cohort Study.

RATIONALE & OBJECTIVE: The lived experience of children with chronic kidney disease (CKD) is poorly characterized. We examined the associations between patient-reported outcome (PRO) scores measuring their fatigue, sleep health, psychological distress, family relationships, and global health with clinical outcomes over time in children, adolescents, and younger adults with CKD and investigated how the PRO scores of this group compare with those of other children, adolescents, and younger adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 212 children, adolescentss, and adults aged 8 to 21 years with CKD and their parents recruited from 16 nephrology programs across North America. PREDICTORS: CKD stage, disease etiology, and sociodemographic and clinical variables. OUTCOME: PRO scores over 2 years. ANALYTICAL APPROACH: We compared PRO scores in the CKD sample with a nationally representative general pediatric population (ages 8 to 17 years). Change of PROs over time and association of sociodemographic and clinical variables with PROs were assessed using multivariable regression models. RESULTS: For all time points, 84% of the parents and 77% of the children, adolescents, and younger adults completed PRO surveys . The baseline PRO scores for the participants with CKD revealed a higher burden of fatigue, sleep-related impairment, psychological distress, impaired global health, and poorer family relationships compared with the general pediatric population, with median score differences≥1 SD for fatigue and global health. The baseline PRO scores did not differ by CKD stage or glomerular versus nonglomerular etiology. Over 2 years, PROs were stable with a<1-point annual change on average on each measure and intraclass correlation coefficients ranging from 0.53 to 0.79, indicating high stability. Hospitalization and parent-reported sleep problems were associated with worse fatigue, psychological health, and global health scores (all P<0.04). LIMITATIONS: We were unable to assess responsiveness to change with dialysis or transplant. CONCLUSIONS: Children with CKD experience a high yet stable burden of impairment across numerous PRO measures, especially fatigue and global health, independent of disease severity. These findings underscore the importance of assessing PROs, including fatigue and sleep measures, in this vulnerable population. PLAIN-LANGUAGE SUMMARY: Children with chronic kidney disease (CKD) have many treatment demands and experience many systemic effects. How CKD impacts the daily life of a child is poorly understood. We surveyed 212 children, adolescents, and younger adults with CKD and their parents over 24 months to assess the participants' well-being over time. Among children, adolescents, and younger adults with CKD we found a very high and persistent burden of psychological distress that did not differ by degree of CKD or type of kidney disease. The participants with CKD endorsed greater impairment in fatigue and global health compared with healthy children, adolescents, and younger adults, and parent-reported sleep problems were associated with poorer patient-reported outcome (PRO) scores across all domains. These findings emphasize the importance of including PRO measures, including fatigue and sleep measures, into routine clinical care to optimize the lived experience of children with CKD.

Clinical course and management of children with IgA vasculitis with nephritis.

BACKGROUND: IgA vasculitis is the most common vasculitis in children and is often complicated by acute nephritis (IgAVN). Risk of chronic kidney disease (CKD) among children with IgAVN remains unknown. This study aimed to describe the clinical management and kidney outcomes in a large cohort of children with IgAVN. METHODS: This observational cohort study used the PEDSnet database to identify children diagnosed with IgAV between January 1, 2009, and February 29, 2020. Demographic and clinical characteristics were compared among children with and without kidney involvement. For children followed by nephrology, clinical course, and management patterns were described. Patients were divided into four categories based on treatment: observation, renin-angiotensin-aldosterone system (RAAS) blockade, corticosteroids, and other immunosuppression, and outcomes were compared among these groups. RESULTS: A total of 6802 children had a diagnosis of IgAV, of whom 1139 (16.7%) were followed by nephrology for at least 2 visits over a median follow-up period of 1.7 years [0.4,4.2]. Conservative management was the most predominant practice pattern, consisting of observation in 57% and RAAS blockade in 6%. Steroid monotherapy was used in 29% and other immunosuppression regimens in 8%. Children receiving immunosuppression had higher rates of proteinuria and hypertension compared to those managed with observation (p < 0.001). At the end of follow-up, 2.6 and 0.5% developed CKD and kidney failure, respectively. CONCLUSIONS: Kidney outcomes over a limited follow-up period were favorable in a large cohort of children with IgAV. Immunosuppressive medications were used in those with more severe presentations and may have contributed to improved outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information.

Skeletal Outcomes in Children and Young Adults with Glomerular Disease.

BACKGROUND: Children with glomerular disease have unique risk factors for compromised bone health. Studies addressing skeletal complications in this population are lacking. METHODS: 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 followed >3 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. RESULTS: 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). CONCLUSIONS: Children and young adults with glomerular disease have significantly higher burden of skeletal complications than the general pediatric population.

White Coat Hypertension Persistence in Children and Adolescents: The Pediatric Nephrology Research Consortium Study.

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM. STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression. RESULTS: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23). CONCLUSIONS: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension.

KDOQI US Commentary on the 2021 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD.

The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the 2021 KDIGO (Kidney Disease: Improving Global Outcomes) guideline for the management of blood pressure in chronic kidney disease (CKD). This commentary is the product of that work group and presents the recommendations and practice points from the KDIGO guideline in the context of US clinical practice. A critical addition to the KDIGO guideline is the recommendation for accurate assessment of blood pressure using standardized office blood pressure measurement. In the general adult population with CKD, KDIGO recommends a goal systolic blood pressure less than 120 mm Hg on the basis of results from the Systolic Blood Pressure Intervention Trial (SPRINT) and secondary analyses of the Action to Control Cardiovascular Risk in Diabetes-Blood Pressure (ACCORD-BP) trial. The KDOQI work group agreed with most of the recommendations while highlighting the weak evidence base especially for patients with diabetes and advanced CKD.

Discordances between pediatric and adult thresholds in the diagnosis of hypertension in adolescents with CKD.

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.

BP in Young Adults with CKD and Associations with Cardiovascular Events and Decline in Kidney Function.

BACKGROUND: BP is an important modifiable risk factor for cardiovascular events and CKD progression in middle-aged or older adults with CKD. However, studies describing the relationship between BP with outcomes in young adults with CKD are limited. METHODS: In an observational study, we focused on 317 young adults (aged 21-40 years) with mild to moderate CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Exposures included baseline systolic BP evaluated continuously (per 10 mm Hg increase) and in categories (<120, 120-129, and ≥130 mm Hg). Primary outcomes included cardiovascular events (heart failure, myocardial infarction, stroke, or all-cause death) and CKD progression (50% decline of eGFR or ESKD). We used Cox proportional hazard models to test associations between baseline systolic BP with cardiovascular events and CKD progression. RESULTS: Cardiovascular events occurred in 52 participants and 161 had CKD progression during median follow-up times of 11.3 years and 4.1 years, respectively. Among those with baseline systolic BP ≥130 mm Hg, 3%/yr developed heart failure, 20%/yr had CKD progression, and 2%/yr died. In fully adjusted models, baseline systolic BP ≥130 mm Hg (versus systolic BP<120 mm Hg) was significantly associated with cardiovascular events or death (hazard ratio [HR], 2.13; 95% confidence interval [95% CI], 1.05 to 4.32) and CKD progression (HR, 1.68; 95% CI, 1.10 to 2.58). CONCLUSIONS: Among young adults with CKD, higher systolic BP is significantly associated with a greater risk of cardiovascular events and CKD progression. Trials of BP management are needed to test targets and treatment strategies specifically in young adults with CKD.

Social Determinants of Cardiovascular Health in African American Children With CKD: An Analysis of the Chronic Kidney Disease in Children (CKiD) Study.

RATIONALE & OBJECTIVE: To identify differences in socioeconomic factors (SES) and subclinical cardiovascular disease (CVD) markers by race among Chronic Kidney Disease in Children (CKiD) participants and determine whether differences in CVD markers persist after adjusting for SES. STUDY DESIGN: Analysis of 3,103 visits with repeated measures from 628 children (497 White participants; 131 African American participants) enrolled in the CKiD study. SETTING & PARTICIPANTS: Children with mild-moderate CKD with at least 1 cardiovascular (CV) parameter (ambulatory blood pressure, left ventricular mass index [LVMI], or lipid profile) measured. EXPOSURE: 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 cause. 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 nonglomerular CKD had more instances of ambulatory hypertension and higher LVMI but more favorable lipid profiles. After adjustment for SES, age, and sex, the magnitude of differences in these CV markers was 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 White children. The degree to which CV markers differ by race is influenced by disease etiology. African Americans with nonglomerular CKD have increased LVMI, more ambulatory hypertension, and favorable lipid profile, but attenuation in magnitude after adjustment for SES was observed. African Americans with glomerular CKD had 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.

Achieved clinic blood pressure level and chronic kidney disease progression in children: a report from the Chronic Kidney Disease in Children cohort.

BACKGROUND: Control of hypertension delays progression of pediatric chronic kidney disease (CKD), yet few data are available regarding what clinic 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 were studied. BP categories were defined as the maximum systolic or diastolic BP percentile (< 50th, 50th to 75th, 75th to 90th, and ≥ 90th percentile) with time-updated classifications corresponding to annual study visits. The primary outcome was time to kidney replacement therapy or a 30% decline in estimated glomerular filtration rate. Cox proportional hazard models described the effect of each BP category compared to BP ≥ 90th percentile. RESULTS: Seven hundred fifty-four participants (median age 9.9 years at study entry) met inclusion criteria; 65% were male and 26% had glomerular CKD. Any BP < 90th percentile was associated with a decreased risk of progression for those with glomerular CKD (hazard ratio (HR), 0.63; 95% CI, 0.28-1.39 (< 50th); HR, 0.59; 95% CI, 0.28-1.26 (50th-75th); HR, 0.40; 95% CI, 0.18-0.93 (75th-90th)). Similar results were found for those with non-glomerular CKD: any BP < 90th percentile was associated with decreased risk of progression (HR, 0.78; 90% CI, 0.49-1.25 (< 50th); HR, 0.53; 95% CI, 0.33-0.84 (50th-75th); HR, 0.71; 95% CI, 0.46-1.08 (75th-90th)). CONCLUSIONS: Achieved clinic BP < 90th percentile was associated with slower CKD progression in children with glomerular or non-glomerular CKD. These data provide guidance for management of children with CKD in the office setting. Graphical abstract.

The CKiD study: overview and summary of findings related to kidney disease progression.

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.

2020 update on the renin-angiotensin-aldosterone system in pediatric kidney disease and its interactions with coronavirus.

The last decade was crucial for our understanding of the renin-angiotensin-aldosterone system (RAAS) as a two-axis, counter-regulatory system, divided into the classical axis, formed by angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and the angiotensin type 1 receptor (AT1R), and the alternative axis comprising angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor. Breakthrough discoveries also took place, with other RAAS endopeptides being described, including alamandine and angiotensin A. In this review, we characterize the two RAAS axes and the role of their components in pediatric kidney diseases, including childhood hypertension (HTN), pediatric glomerular diseases, congenital abnormalities of the kidney and urinary tract (CAKUT), and chronic kidney disease (CKD). We also present recent findings on potential interactions between the novel coronavirus, SARS-CoV-2, and components of the RAAS, as well as potential implications of coronavirus disease 2019 (COVID-19) for pediatric kidney diseases.

L-type calcium channel blocker use and proteinuria among children with chronic kidney diseases.

BACKGROUND: Hypertension is common among children with chronic kidney disease (CKD), and dihydropyridine calcium channel blockers (dhCCBs) are frequently used as treatment. The impact of dhCCBs on proteinuria in children with CKD is unclear. METHODS: Data from 722 participants in the Chronic Kidney Disease in Children (CKiD) longitudinal cohort with a median age of 12 years were used to assess the association between dhCCBs and log transformed urine protein/creatinine levels as well as blood pressure control measured at annual visits. Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use was evaluated as an effect measure modifier. RESULTS: Individuals using dhCCBs had 18.8% higher urine protein/creatinine levels compared to those with no history of dhCCB or ACEi and ARB use. Among individuals using ACEi and ARB therapy concomitantly, dhCCB use was not associated with an increase in proteinuria. Those using dhCCBs had higher systolic and diastolic blood pressures. CONCLUSIONS: Use of dhCCBs in children with CKD and hypertension is associated with higher levels of proteinuria and was not found to be associated with improved blood pressure control.

Conversion to permanent vascular access is associated with improved markers of hemodialysis efficacy in children: Pediatric nephrology research consortium study.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.