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Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.
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OBJECTIVE: To describe the epidemiology of reclassification of prehypertensive and unclassified adolescents by 2022 American Heart Association pediatric ambulatory blood pressure monitoring (ABPM) guidelines, and to evaluate the association of the new diagnostic categories with left ventricular hypertrophy (LVH). STUDY DESIGN: A single-center, retrospective review of ABPM reports from adolescents 13-21 years old, from 2015 through 2022, was performed. Adolescents with prehypertension or unclassified by 2014 guidelines were reclassified by 2022 definitions. Logistic regression models evaluated the association of reclassification phenotypes with LVH. RESULTS: A majority of prehypertensive adolescents reclassified to hypertension (70%, n = 49/70). More than one-half (57%, n = 28/49) of the hypertension was isolated nocturnal hypertension, and 80% was systolic hypertension. Reclassification to hypertension was more common in males. The majority (55.6%) of unclassified adolescents were reclassified to normotension. No demographic or clinical variables were associated with reclassification categories. LVH was not associated with hypertension in the reclassified prehypertensive or unclassified groups. CONCLUSIONS: The 2022 ABPM guidelines clearly define blood pressure phenotypes. However, reclassification to hypertension was not associated with an increased odds of LVH. Because most prehypertensive adolescents reclassified as hypertensive by nighttime BPs alone, this study highlights the lowered threshold for nocturnal hypertension. Prospective studies in larger, well-defined cohorts are needed to describe better the predictive value of 2022 BP phenotypes for target organ damage.
Subject(s)
Hypertension , Prehypertension , Male , Humans , Child , Adolescent , Young Adult , Adult , Blood Pressure , Prehypertension/diagnosis , Prehypertension/epidemiology , Blood Pressure Monitoring, Ambulatory , Prospective Studies , American Heart Association , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/complications , Hypertrophy, Left Ventricular/diagnosis , Hypertrophy, Left Ventricular/epidemiology , Hypertrophy, Left Ventricular/etiologyABSTRACT
INTRODUCTION: Fibroblast growth factor 23 (FGF23) has direct effects on the vasculature and myocardium, and high levels of FGF23 are a risk factor for cardiovascular disease (CVD); however, the impact of FGF23 on CVD in primary proteinuric glomerulopathies has not been addressed. METHODS: The associations of baseline plasma intact FGF23 levels with resting blood pressure (BP) and lipids over time among adults and children with proteinuric glomerulopathies enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were analyzed using generalized estimating equation regression analyses. Models were adjusted for age, sex, glomerular diagnosis, follow-up time, estimated glomerular filtration rate, urine protein/creatinine ratio, obesity, and serum phosphorous levels. RESULTS: Two hundred and four adults with median FGF23 77.5 (IQR 51.3-119.3) pg/mL and 93 children with median FGF23 62.3 (IQR 44.6-83.6) pg/mL were followed for a median of 42 (IQR 20.5-54) months. In adjusted models, each 1 µg/mL increase in FGF23 was associated with a 0.3 increase in systolic BP index at follow-up (p < 0.001). Greater baseline FGF23 was associated with greater odds of hypertensive BP (OR = 1.0003; 95% CI 1.001-1.006, p = 0.03) over time. Compared to tertile 1, tertile 2 (OR = 2.1; 95% CI 1.12-3.99, p = 0.02), and tertile 3 (OR = 3; 95% CI 1.08-8.08, p = 0.04), FGF23 levels were associated with greater odds of hypertensive BP over time. Tertile 2 was associated with greater triglycerides compared to tertile 1 (OR = 48.1; 95% CI 4.4-91.9, p = 0.03). CONCLUSION: Overall, higher baseline FGF23 was significantly associated with hypertensive BP over time in individuals with proteinuric glomerulopathies. Further study of FGF23 as a therapeutic target for reducing CVD in proteinuric glomerular disease is warranted.
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Cardiovascular Diseases , Hypertension , Adult , Child , Humans , Blood Pressure/physiology , Fibroblast Growth Factor-23 , Fibroblast Growth Factors , Risk FactorsABSTRACT
BACKGROUND: In adults, caffeine has protective effects against kidney dysfunction and type 2 diabetes mellitus (T2DM) but increases the risk of acute blood pressure (BP) elevation and dyslipidemia. These relationships are unclear in adolescents. This study aimed to determine the association between caffeine intake and markers of childhood cardiometabolic risk, hypothesizing that higher caffeine intake would be associated with elevated BP and dyslipidemia but improved kidney function and insulin sensitivity. METHODS: Adolescents ages 13-17 who participated in the National Health and Nutritional Examination Survey (NHANES) from 2011 to 2018 and completed 24-h dietary recalls were included. Logistic and linear regression models were used to analyze cross-sectional associations between caffeine and cardiometabolic risk factors. RESULTS: The mean participant age was 15.0 years, with a sex distribution of 49.9% male and 50.1% female. In fully adjusted regression models, higher caffeine intake was not associated with any changes in BP (OR = 0.78, 95%CI [0.52,1.16], p = 0.21), dyslipidemia (OR = 0.91, 95%CI [0.65,1.27], p = 0.57), glomerular hyperfiltration (OR = 1.01, 95%CI [0.60,1.71], p = 0.96), albuminuria (OR = 0.94, 95%CI [0.45,1.98], p = 0.87), or insulin resistance (OR = 1.15, 95%CI [0.85,1.56], p = 0.36). CONCLUSION: Contrary to its cardiometabolic effects in adults, caffeine intake was not associated with an increased or reduced risk of kidney dysfunction, T2DM, hypertension, or dyslipidemia in adolescents. IMPACT: Although the effects of caffeine intake on cardiometabolic risk have been well defined in adults, data exploring its impact on adolescent cardiovascular and metabolic function is limited. The goal of this study was to understand the relationship between caffeine intake and markers of childhood cardiometabolic risk. Unlike its established effects in adults, caffeine consumption showed no association with markers of cardiometabolic disease, such as kidney dysfunction, type 2 diabetes mellitus, blood pressure, dyslipidemia, or hyperuricemia in adolescents. These findings offer novel insight into the effects of caffeine on cardiometabolic function in adolescents, which may guide clinical recommendations for at-risk patients.
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BACKGROUND: Ischemic optic neuropathy (ION) is exceedingly rare in children on dialysis, resulting from poor perfusion of the optic nerve, and presents as sudden acute painless vision loss. CASE-DIAGNOSIS/TREATMENT: We report the case of a 3-year-old male with stage 5 chronic kidney disease (CKD 5) due to focal segmental glomerulosclerosis (FSGS) status post-bilateral nephrectomy on chronic hemodialysis who had acute loss of vision several hours after a hemodialysis session. Earlier that day, he had a drop in blood pressure intra-dialysis to 89/67 mmHg, with at home blood pressures ranging 90/60 to 150/100 mmHg. The patient was treated with tight blood pressure control to maintain blood flow and prevent blood pressure lability, received high-dose corticosteroids with a corticosteroid taper, and placed on high-dose erythropoietin for neuroprotective effect. He regained partial vision beginning approximately 1 month after presentation. CONCLUSIONS: The exact cause of our patient's simultaneous bilateral anterior and posterior ION, confirmed via MRI and fundoscopic examination, is unclear; however, is likely secondary to a combination of fluctuating blood pressure, anemia, anephric status, and hemodialysis. This highlights the need for close blood pressure monitoring, management of anemia, and more diligent ophthalmologic screening in pediatric patients on chronic hemodialysis.
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Anemia , Glomerulosclerosis, Focal Segmental , Kidney Failure, Chronic , Optic Neuropathy, Ischemic , Male , Humans , Child , Child, Preschool , Optic Neuropathy, Ischemic/complications , Optic Neuropathy, Ischemic/diagnosis , Renal Dialysis/adverse effects , Glomerulosclerosis, Focal Segmental/complications , Kidney Failure, Chronic/therapy , Anemia/etiologyABSTRACT
Primary glomerular diseases are rare entities. This has hampered efforts to better understand the underlying pathobiology and to develop novel safe and effective therapies. NEPTUNE is a rare disease network that is focused on patients of all ages with minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. It is a longitudinal cohort study that collects detailed demographic, clinical, histopathologic, genomic, transcriptomic, and metabolomic data. The goal is to develop a molecular classification for these disorders that supersedes the traditional pathological features-based schema. Pediatric patients are important contributors to this ongoing project. In this review, we provide a snapshot of the children and adolescents enrolled in NEPTUNE and summarize some key observations that have been made based on the data accumulated during the study. In addition, we describe the development of NEPTUNE Match, a program that aims to leverage the multi-scalar information gathered for each individual patient to provide guidance about potential clinical trial participation based on the molecular characterization and non-invasive biomarker profile. This represents the first organized effort to apply principles of precision medicine to the treatment of patients with primary glomerular disease. NEPTUNE has proven to be an invaluable asset in the study of glomerular diseases in patients of all ages including children and adolescents.
Subject(s)
Glomerulosclerosis, Focal Segmental , Humans , Child , Adolescent , Glomerulosclerosis, Focal Segmental/genetics , Male , Female , Glomerulonephritis, Membranous/pathology , Glomerulonephritis, Membranous/genetics , Longitudinal Studies , Nephrosis, Lipoid/diagnosis , Rare Diseases/genetics , Rare Diseases/therapy , Rare Diseases/diagnosis , Child, Preschool , Cohort Studies , Precision Medicine/methodsABSTRACT
BACKGROUND: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression. METHODS: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression. RESULTS: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (ß - 7.5 × 10-6, CI - 1.2 × 10-5, - 3 × 10-6, p = 0.001) and incident cases of NS (vs. prevalent) (ß - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (ß 0.16, CI 0.04, 0.29, p = 0.01) over time. CONCLUSION: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.
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Body Height , Nephrotic Syndrome , Humans , Nephrotic Syndrome/drug therapy , Male , Female , Child , Child, Preschool , Body Height/drug effects , Adolescent , Growth Disorders/etiology , Growth Disorders/drug therapy , Growth Disorders/diagnosis , Longitudinal Studies , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Rituximab/administration & dosage , Rituximab/adverse effectsABSTRACT
BACKGROUND: In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response. METHODS: A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia. RESULTS: Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time. CONCLUSIONS: Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.
Subject(s)
Blood Pressure , Dyslipidemias , Hypertension , Nephrotic Syndrome , Humans , Nephrotic Syndrome/urine , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/complications , Nephrotic Syndrome/epidemiology , Nephrotic Syndrome/blood , Male , Child , Female , Longitudinal Studies , Hypertension/epidemiology , Hypertension/drug therapy , Hypertension/diagnosis , Hypertension/etiology , Child, Preschool , Dyslipidemias/epidemiology , Dyslipidemias/blood , Adolescent , Lipids/blood , Prevalence , InfantABSTRACT
BACKGROUND: Membranous-like glomerulopathy with masked monoclonal IgG deposits (MGMID) is a newly recognized condition predominantly observed in young females, and its understanding in the pediatric population remains limited. MATERIALS AND METHODS: Four cases of MGMID are reported, including three pediatric patients. RESULTS: All patients were female, with ages ranging from 12 to 26 years. None of the patients had malignancies. They presented with kidney dysfunction, proteinuria, or hematuria. Kidney biopsies of all cases exhibited a membranous pattern of injury with monoclonal IgG-κ restriction, "unmasked" by pronase digestion. Pediatric cases were treated conservatively, while the adult case underwent immunosuppressive treatment. All patients had favorable outcomes, and none reached end stage kidney disease (ESKD). CONCLUSION: MGMID can affect both adult and pediatric patients. Further studies are needed to fully characterize its risk factors, optimal therapy, and outcomes.
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Glomerulonephritis, Membranous , Immunoglobulin G , Humans , Female , Glomerulonephritis, Membranous/pathology , Glomerulonephritis, Membranous/immunology , Glomerulonephritis, Membranous/complications , Child , Adult , Adolescent , Young Adult , Biopsy , Immunosuppressive Agents/therapeutic use , Treatment OutcomeABSTRACT
PURPOSE: This work aims to assess the association of sleep duration with cardiometabolic risk (adiposity, blood pressure, lipids, albuminuria and A1C) and to investigate lifestyle factors (physical activity, light exposure, caffeine consumption and sugar consumption) associated with sleep duration in children. METHODS: A nationally representative sample of 3907 children ages 6-17 years enrolled in NHANES from 2011 to 2014 was included in this cross-sectional study. Sleep duration was defined as the daily average time spent sleeping over 7 days as measured by a physical activity monitor (PAM). Participants without valid sleep data for ≥95% of the study were excluded. Regression models were adjusted for age, sex, race, body mass index (BMI) Z score, physical activity and light exposure. RESULTS: In adjusted regression models, longer sleep duration was associated with lower systolic blood pressure index (ß = -3.63 * 10-5, 95% CI -6.99 * 10-5, -2.78 * 10-6, p = 0.035) and BMI Z score (ß = -0.001, 95% CI -0.001, 0.000, p = 0.002). In logistic regression models, longer sleep duration was associated with lower odds of obesity (OR = 0.998, 95% CI 0.997, 0.999, p < 0.001) and overweight status (OR = 0.998, 95% CI 0.997, 0.999, p = 0.004). Greater light exposure (ß = 6.64 * 10-5, 95% CI 3.50 * 10-5, 9.69 * 10-5, p < 0.001) and physical activity (ß = 0.005, 95% CI 0.004, 0.006, p < 0.001) were associated with longer sleep. CONCLUSION: Longer sleep duration was associated with lower blood pressure and adiposity measures in children. Improving sleep quality by increasing physical activity and light exposure in childhood may decrease the lifetime risk of cardiometabolic disease.
Subject(s)
Cardiometabolic Risk Factors , Nutrition Surveys , Sleep , Humans , Child , Adolescent , Female , Male , United States/epidemiology , Cross-Sectional Studies , Sleep/physiology , Exercise , Body Mass Index , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Time Factors , Pediatric Obesity/epidemiology , Blood Pressure/physiology , Life Style , Risk Factors , Sleep DurationABSTRACT
OBJECTIVE: To determine the association between dietary fiber intake and markers of cardiometabolic risk in adolescents, with blood pressure (BP) as the primary outcome of interest and secondary outcome measures including other established markers of childhood cardiometabolic risk, such as obesity, lipids, albuminuria, estimated glomerular filtration rate (eGFR), and uric acid. STUDY DESIGN: Dietary fiber intake was assessed by two 24-hour dietary recall interviews, which were averaged and corrected for body weight. Logistic and linear regression models were used to analyze the cross-sectional association between dietary fiber and cardiometabolic markers. Participants aged 13-17 years in the National Health and Nutritional Examination Survey 2009-2018 who completed a 24-hour dietary recall survey were included. Exclusion criteria included pregnancy, small for gestational age status, and history of major health comorbidities. RESULTS: In fully adjusted regression models, low dietary fiber intake was significantly associated with greater diastolic blood pressure (ß = -13.29; 95% CI, -20.66 to -5.93), body mass index z-score (ß = -0.91; 95% CI, -1.47 to -0.34), and uric acid (ß = -0.80; 95% CI, -1.44 to -0.16). CONCLUSIONS: The association found between low dietary fiber intake and poor childhood cardiometabolic risk markers indicate a need for prospective studies using fiber intake as a dietary intervention in childhood and as a tool for prevention of many chronic conditions.
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Cardiometabolic Risk Factors , Cardiovascular Diseases , Humans , Adolescent , United States/epidemiology , Risk Factors , Cross-Sectional Studies , Prospective Studies , Uric Acid , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Diet/adverse effects , Dietary FiberABSTRACT
RATIONALE & OBJECTIVE: The effects of race, ethnicity, socioeconomic status (SES), and disease severity on acute care utilization in patients with glomerular disease are unknown. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 1,456 adults and 768 children with biopsy-proven glomerular disease enrolled in the Cure Glomerulonephropathy (CureGN) cohort. EXPOSURE: Race and ethnicity as a participant-reported social factor. OUTCOME: Acute care utilization defined as hospitalizations or emergency department visits. ANALYTICAL APPROACH: Multivariable recurrent event proportional rate models were used to estimate associations between race and ethnicity and acute care utilization. RESULTS: Black or Hispanic participants had lower SES and more severe glomerular disease than White or Asian participants. Acute care utilization rates were 45.6, 29.5, 25.8, and 19.2 per 100 person-years in Black, Hispanic, White, and Asian adults, respectively, and 55.8, 42.5, 40.8, and 13.0, respectively, for children. Compared with the White race (reference group), Black race was significantly associated with acute care utilization in adults (rate ratio [RR], 1.76 [95% CI, 1.37-2.27]), although this finding was attenuated after multivariable adjustment (RR, 1.31 [95% CI, 1.03-1.68]). Black race was not significantly associated with acute care utilization in children; Asian race was significantly associated with lower acute care utilization in children (RR, 0.32 [95% CI 0.14-0.70]); no significant associations between Hispanic ethnicity and acute care utilization were identified. LIMITATIONS: We used proxies for SES and lacked direct information on income, household unemployment, or disability. CONCLUSIONS: Significant differences in acute care utilization rates were observed across racial and ethnic groups in persons with prevalent glomerular disease, although many of these difference were explained by differences in SES and disease severity. Measures to combat socioeconomic disadvantage in Black patients and to more effectively prevent and treat glomerular disease are needed to reduce disparities in acute care utilization, improve patient wellbeing, and reduce health care costs.
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Ethnicity , Healthcare Disparities , Kidney Diseases , Patient Acceptance of Health Care , Adult , Child , Humans , Black People , Hispanic or Latino , Prospective Studies , Social Class , Asian People , White People , Patient Acceptance of Health Care/ethnologyABSTRACT
PURPOSE OF REVIEW: This review highlights the major changes reflected in the 2022 American Heart Association (AHA) Scientific Statement on Ambulatory Blood Pressure Monitoring (ABPM) in Children and Adolescents with a specific focus on the newly defined phenotypes of hypertension and their epidemiology and associated outcomes. RECENT FINDINGS: The 2022 AHA guidelines' most notable changes include the following: (1) alignment of blood pressure (BP) thresholds with the 2017 American Academy of Pediatrics (AAP) clinical practice guidelines, 2017 American College of Cardiology (ACC)/AHA hypertension guidelines, and 2016 European Society of Hypertension (ESH) pediatric recommendations; (2) expansion of the use of ABPM to diagnose and phenotype pediatric hypertension in all pediatric patients; (3) removal of BP loads from diagnostic criteria; and (4) simplified classification of new hypertension phenotypes to prognosticate risks and guide clinical management. Recent studies suggest that utilizing the 2022 AHA pediatric ABPM guidelines will increase the prevalence of pediatric ambulatory hypertension, especially for wake ambulatory hypertension in older, taller males and for nocturnal hypertension in both males and females ≥ 8 years of age. The new definitions simplify the ambulatory hypertension criteria to include only the elements most predictive of future health outcomes, increase the sensitivity of BP thresholds in alignment with recent data and other guidelines, and thus make hypertension diagnoses more clinically meaningful. This guideline will also aid in the transition of adolescents and young adults to adult medical care. Further studies will be necessary to study ambulatory BP norms in a more diverse pediatric population and evaluate the impact of these guidelines on prevalence and future outcomes.
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Hypertension , Male , Female , Humans , Child , United States , Blood Pressure Monitoring, Ambulatory , Blood Pressure/physiology , Blood Pressure Determination , PhenotypeABSTRACT
BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2. Long-term consequences of MIS-C remain unknown. The objective was to describe the prevalence and clinical predictors of hypertension (HTN) and elevated blood pressure (BP) following MIS-C. METHODS: A retrospective study of children ≤ 18 years admitted to a tertiary center with MIS-C was performed. HTN and elevated BP were classified as per the 2017 American Academy of Pediatrics Clinical Practice Guidelines and indexed to the 95th percentile. Data included demographics, inpatient clinical measures, and echocardiograms over 1-year follow-up. Data were analyzed using Kruskal-Wallis, chi-square, and logistic regression. RESULTS: Among 63 children hospitalized with MIS-C (mean age 9.7 ± 4.2 years, 58.7% male, body mass index (BMI) z-score 0.59 ± 1.9), 14% had HTN, and 4% had elevated BP > 30 days post-hospitalization. Multivariate linear regression analysis showed that BMI z-score was significantly associated with higher mean systolic (ß = 2.664, CI = 1.307-3.980, p < 0.001) and diastolic (ß = 2.547, CI = 0.605-4.489, p = 0.012) BP index > 30 days post-hospitalization. Acute kidney injury (AKI) (23.8%) (OR = 2.977, CI = 1.778-4.987, p < 0.001), peak inpatient serum creatinine (OR = 2.524, CI = 1.344-4.740, p = 0.004), and maximum CRP (OR = 1.009, CI = 1.002-1.016, p = 0.014) were all associated with increased odds of post-hospitalization HTN. Left ventricular hypertrophy was present in 46% while hospitalized, compared to 10% at last follow-up. All had return of normal systolic function. CONCLUSIONS: Post-hospitalization HTN and elevated BP may be associated with MIS-C. Children with greater BMI or AKI may be at greater risk for developing HTN after MIS-C. MIS-C follow-up requires careful BP monitoring and antihypertensive medication consideration. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Acute Kidney Injury , Autonomic Nervous System Diseases , COVID-19 , Hypertension , Child , Humans , Male , Child, Preschool , Adolescent , Female , COVID-19/complications , COVID-19/epidemiology , SARS-CoV-2 , Retrospective Studies , Hypertension/drug therapy , Hypertension/epidemiology , Hypertension/etiologyABSTRACT
BACKGROUND: Pediatric chronic disease impacts the affected child and their family structure. There is limited literature investigating the psychosocial impact of nephrotic syndrome on families. METHODS: Caregivers of children with nephrotic syndrome completed two validated surveys: (1) Impact on Family (IOF) that evaluates the family impact (degree to which family is affected by a pediatric chronic illness) and (2) Coping Health Inventory for Parents (CHIP) that examines the coping patterns used by caregivers. Linear regression models were utilized to determine predictors of perceived family impact and coping patterns. RESULTS: Seventy-five caregivers of a child with nephrotic syndrome completed the surveys. On a scale from low impact to significant impact to very serious impact, results indicated that nephrotic syndrome had a significant impact on families (mean revised IOF total score 33.04 ± 9.38). Families in the steroid-resistant nephrotic syndrome (SRNS) group reported a higher financial impact compared to the steroid-sensitive nephrotic syndrome (SSNS) group (p = 0.03). Families in the frequently relapsing group (FRNS) reported a higher impact on the caregiver's ability to cope with the child's condition compared to the SRNS group (p = 0.02). Tacrolimus use was associated with increasing the perceived family impact (ß = 4.76, p = 0.046). CHIP scores indicated that caregivers did not cope well with family integration (component I) but coped well with social support (component II) and communication (component III). CONCLUSIONS: Childhood nephrotic syndrome has a significant overall perceived impact on the family, and caregivers did not cope well regarding strengthening their family life. These findings can be used as outcome measures for future intervention studies to find solutions that would decrease the perceived family burden. A higher resolution version of the Graphical abstract is available as Supplementary information.
Subject(s)
Nephrotic Syndrome , Child , Humans , Nephrotic Syndrome/drug therapy , Caregivers/psychology , Adaptation, Psychological , Recurrence , Chronic DiseaseABSTRACT
BACKGROUND: Diagnosing genetic kidney disease has become more accessible with low-cost, rapid genetic testing. The study objectives were to determine genetic testing diagnostic yield and examine predictors of genetic diagnosis in children with nephrolithiasis/nephrocalcinosis (NL/NC). METHODS: This retrospective multicenter cross-sectional study was conducted on children ≤ 21 years old with NL/NC from pediatric nephrology/urology centers that underwent the Invitae Nephrolithiasis Panel 1/1/2019-9/30/2021. The diagnostic yield of the genetic panel was calculated. Bivariate and multiple logistic regression were performed to assess for predictors of positive genetic testing. RESULTS: One hundred and thirteen children (83 NL, 30 NC) from 7 centers were included. Genetic testing was positive in 32% overall (29% NL, 40% NC) with definite diagnoses (had pathogenic variants alone) made in 11.5%, probable diagnoses (carried a combination of pathogenic variants and variants of uncertain significance (VUS) in the same gene) made in 5.4%, and possible diagnoses (had VUS alone) made in 15.0%. Variants were found in 28 genes (most commonly HOGA1 in NL, SLC34A3 in NC) and 20 different conditions were identified. Compared to NL, those with NC were younger and had a higher proportion with developmental delay, hypercalcemia, low serum bicarbonate, hypophosphatemia, and chronic kidney disease. In multivariate analysis, low serum bicarbonate was associated with increased odds of genetic diagnosis (ß 2.2, OR 8.7, 95% CI 1.4-54.7, p = 0.02). CONCLUSIONS: Genetic testing was high-yield with definite, probable, or possible explanatory variants found in up to one-third of children with NL/NC and shows promise to improve clinical practice. A higher resolution version of the Graphical abstract is available as Supplementary information.
Subject(s)
Kidney Calculi , Nephrocalcinosis , Nephrolithiasis , Child , Humans , Young Adult , Adult , Nephrocalcinosis/diagnosis , Nephrocalcinosis/genetics , Bicarbonates , Cross-Sectional Studies , Nephrolithiasis/diagnosis , Nephrolithiasis/genetics , Kidney Calculi/genetics , Genetic TestingABSTRACT
BACKGROUND: Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects. METHODS: Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration. RESULTS: Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001). CONCLUSION: Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown. CLINICAL TRIAL: NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.
Subject(s)
Kidney Diseases , Vitamin D Deficiency , Humans , Child , Young Adult , Vitamin D , Cholecalciferol/therapeutic use , Vitamins/therapeutic use , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Kidney Diseases/complications , Dietary Supplements , Proteinuria/etiology , Proteinuria/complicationsABSTRACT
BACKGROUND: Tobacco exposure has been recognized as a risk factor for cardiovascular disease (CVD) and progression of kidney disease. Patients with proteinuric glomerulopathies are at increased risk for cardiovascular morbidity and mortality. Multiple studies have linked tobacco exposure to CVD and chronic kidney disease, but the relationships between smoking and proteinuric glomerulopathies in adults and children have not been previously explored. METHODS: Data from the Nephrotic Syndrome Study Network (NEPTUNE), a multi-center prospective observational study of participants with proteinuric glomerulopathies, was analyzed. 371 adults and 192 children enrolled in NEPTUNE were included in the analysis. Self-reported tobacco exposure was classified as non-smoker, active smoker, former smoker, or exclusive passive smoker. Baseline serum cotinine levels were measured in a sub-cohort of 178 participants. RESULTS: The prevalence of active smokers, former smokers and exclusive passive smoking among adults at baseline was 14.6%, 29.1% and 4.9%, respectively. Passive smoke exposure was 16.7% among children. Active smoking (reference non-smoking) was significantly associated with greater total cholesterol among adults (ß 17.91 95% CI 0.06, 35.76, p = 0.049) while passive smoking (reference non-smoking) was significantly associated with greater proteinuria over time among children (ß 1.23 95% CI 0.13, 2.33, p = 0.03). Higher cotinine levels were associated with higher baseline eGFR (r = 0.17, p = 0.03). CONCLUSION: Tobacco exposure is associated with greater risk for CVD and worse kidney disease outcomes in adults and children with proteinuric glomerulopathies. Preventive strategies to reduce tobacco exposure may help protect against future cardiovascular and kidney morbidity and mortality in patients with proteinuric glomerulopathies.
Subject(s)
Cardiovascular Diseases , Kidney Diseases , Tobacco Smoke Pollution , Humans , Adult , Child , Cohort Studies , Cotinine , Nicotiana , Tobacco Smoke Pollution/adverse effects , Neptune , Kidney Diseases/chemically inducedABSTRACT
Pediatric hypertension (HTN) has demonstrated an upward trend in recent years. Adolescent HTN has been linked to adult HTN, cardiovascular disease, and other health conditions. Thus, it is essential that HTN and its associated cardiac abnormalities be diagnosed and treated early to minimize lifelong adverse effects. In this study, we evaluated whether vortex formation time (VFT), a validated echocardiogram measure of left ventricular diastolic dysfunction, correlated with ambulatory blood pressure monitoring (ABPM) and HTN in adolescents. Echocardiogram data including systolic and diastolic function indices and ABPM data from 2015 to 2022 in adolescents age 13-21 years were analyzed retrospectively. We found that VFT was significantly lower in adolescents with HTN compared to those without HTN (3.69 ± 1.39 vs. 4.50 ± 1.73, p = 0.02). Standard echocardiographic indices of systolic and diastolic function were similar between the two groups, except indexed left atrial volume. Higher overall systolic blood pressure (SBP) (ß = - 0.01, CI - 0.02, - 2.2 × 10-3, p = 0.02), mean wake SBP (ß = - 0.01, CI - 0.02, - 9.4 × 10-4, p = 0.03), and mean sleep SBP (ß = - 0.01, CI - 0.02, - 1.2 × 10-3, p = 0.03) were significantly associated with lower VFT. This study demonstrates that VFT correlates to ABPM data and can be used a novel diagnostic measure in adolescents with HTN.
Subject(s)
Hypertension , Ventricular Dysfunction, Left , Adult , Humans , Adolescent , Child , Young Adult , Blood Pressure Monitoring, Ambulatory , Retrospective Studies , Hypertension/diagnosis , Echocardiography , Blood PressureABSTRACT
Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents myriad questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anticomplement therapy trials either planned or under way, the National Kidney Foundation facilitated an all-virtual scientific workshop entitled "Improving Clinical Trials for Anti-Complement Therapies in Complement-Mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anticomplement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, participant risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.