Characterization of the Urinary Metagenome and Virome in Healthy Children.

Recent advances in next-generation sequencing and metagenomic studies have provided insights into the microbial profile of different body sites. However, research on the microbial composition of urine is limited, particularly in children. The goal of this study was to optimize and develop reproducible metagenome and virome protocols using a small volume of urine samples collected from healthy children. We collected midstream urine specimens from 40 healthy children. Using the metagenomics shotgun approach, we tested various protocols. Different microbial roots such as Archaea, Bacteria, Eukaryota, and Viruses were successfully identified using our optimized urine protocol. Our data reflected much variation in the microbial fingerprints of children. Girls had significantly higher levels of Firmicutes, whereas boys had significantly higher levels of Actinobacteria. The genus Anaerococcus dominated the urinary bacteriome of healthy girls, with a significant increase in Anaerococcus prevotii, Anaerococcus vaginalis, and Veillonella parvula (p-value < 0.001) when compared with that of boys. An increased relative abundance of Xylanimonas and Arthrobacter, with a significantly high abundance of Arthrobacter sp. FB24 (p-value 0.0028) and Arthrobacter aurescences (p-value 0.015), was observed in boys. The urinary mycobiome showed a significant rise in the genus Malassezia and Malassezia globose fungus (p-value 0.009) in girls, whereas genus Saccharomyces (p-value 0.009) was significantly high in boys. The beta diversity of the urinary mycobiome was found to differ between different age groups. Boys had significantly more Mastadenovirus and Human mastadenovirus-A in their urinary virome than girls. With increasing age, we noticed an increase in the relative abundance of the order Caudovirales. Our optimized protocols allowed us to identify the unique microbes for each sex by using an adequate volume of urine (3−10 mL) to screen for the bacteriome, mycobiome, and virome profiles in the urine of healthy children. To the best of our knowledge, this is the first study to characterize the metagenomics profiles of urine in a healthy pediatric population.

Bifidobacterium reduction is associated with high blood pressure in children with type 1 diabetes mellitus.

Children with Type 1 diabetes mellitus (T1DM) have an elevated risk of abnormal blood pressure (BP) measurements and patterns. Both hypertension and T1DM are well-known risk factors for cardiovascular disease and kidney failure. The human microbiome has been linked to both diabetes and hypertension, but the relationship between the gut microbiome and BP in children with T1DM is not well-understood. In this cross-sectional study, we examined the relationship between resting office BP and gut microbiota composition, diversity, and richness in children with T1DM and healthy controls. We recruited 29 pediatric subjects and divided them into three groups: healthy controls (HC, n = 5), T1DM with normal BP (T1DM-Normo, n = 17), and T1DM with elevated BP (T1DM-HBP, n = 7). We measured the BP, dietary and clinical parameters for each subject. We collected fecal samples to perform the 16s rDNA sequencing and to measure the short-chain fatty acids (SCFAs) level. The microbiome downstream analysis included the relative abundance of microbiota, alpha and beta diversity, microbial markers using Linear Discriminant effect size analysis (LEfSe), potential gut microbial metabolic pathways using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) and metabolic pathways validation using Statistical Inference of Associations between Microbial Communities And host phenotype (SIAMCAT) machine learning toolbox. Our study results showed that T1DM-HBP group had distinct gut microbial composition (at multiple taxonomic levels) and reduced diversity (richness and abundance) compared with T1DM-Normo and HC groups. Children with T1DM-HBP showed a significant reduction of Bifidobacterium levels (especially B. adolescentis, B. bifidum, and B. longum) compared to the T1DM-Normo group. We also observed unique gut-microbial metabolic pathways, such as elevated lipopolysaccharide synthesis and glutathione metabolism in children with T1DM-HBP compared to T1DM-Normo children. We can conclude that the reduction in the abundance of genus Bifidobacterium could play a significant role in elevating the BP in pediatric T1DM subjects. More studies are needed to corroborate our findings and further explore the potential contributing mechanisms we describe.

Case Report: Recurring Peritonitis and Dialysis Failure in a Toddler on Peritoneal Dialysis.

We report a case of a 2-year-old-boy with end stage renal disease (ESRD) secondary to posterior urethral valves (PUV) on peritoneal dialysis (PD). Our patient developed multiple episodes of peritonitis, refractory anemia and feeding intolerance over a 12-month-period. He was treated with multiple courses of intraperitoneal antibiotics. Despite being on high-calorie formula, he was slowly thriving. The feeding intolerance was attributed to past history of prematurity, gastro-esophageal reflux disease and ESRD co-morbidities. He had anemia resistant to erythrocyte stimulating agents and iron supplementation. His family received re-training and mastered the PD techniques. They reported no breach of the aseptic techniques. His workup which included multiple AP abdominal XR-plain films were read as unremarkable and showed the gastrostomy tube (GT) and the PD catheter in good position. He completed his antibiotic courses as prescribed after each peritonitis episode, peritoneal fluid cultures repeated after each treatment completion showed no growth. During the last peritonitis episode, our patient developed ultrafiltration failure. A cross-table abdominal XR was obtained to evaluate the peritoneal catheter position and showed an intra-abdominal foreign body. During surgery, a needle was laparoscopically removed from the ileum and the PD catheter was replaced. Subsequently, our patient's feeding intolerance and resistant anemia resolved. Finally PD was successfully resumed.

The Human Microbiome in Chronic Kidney Disease: A Double-Edged Sword.

Chronic kidney disease (CKD) is an increasing global health burden. Current treatments for CKD include therapeutics to target factors that contribute to CKD progression, including renin-angiotensin-aldosterone system inhibitors, and drugs to control blood pressure and proteinuria control. Recently, associations between chronic disease processes and the human microbiota and its metabolites have been demonstrated. Dysbiosis-a change in the microbial diversity-has been observed in patients with CKD. The relationship between CKD and dysbiosis is bidirectional; gut-derived metabolites and toxins affect the progression of CKD, and the uremic milieu affects the microbiota. The accumulation of microbial metabolites and toxins is linked to the loss of kidney functions and increased mortality risk, yet renoprotective metabolites such as short-chain fatty acids and bile acids help restore kidney functions and increase the survival rate in CKD patients. Specific dietary interventions to alter the gut microbiome could improve clinical outcomes in patients with CKD. Low-protein and high-fiber diets increase the abundance of bacteria that produce short-chain fatty acids and anti-inflammatory bacteria. Fluctuations in the urinary microbiome are linked to increased susceptibility to infection and antibiotic resistance. In this review, we describe the potential role of the gut, urinary and blood microbiome in CKD pathophysiology and assess the feasibility of modulating the gut microbiota as a therapeutic tool for treating CKD.

Antihypertensive agents: a long way to safe drug prescribing in children.

Recently updated clinical guidelines have highlighted the gaps in our understanding and management of pediatric hypertension. With increased recognition and diagnosis of pediatric hypertension, the use of antihypertensive agents is also likely to increase. Drug selection to treat hypertension in the pediatric patient population remains challenging. This is primarily due to a lack of large, well-designed pediatric safety and efficacy trials, limited understanding of pharmacokinetics in children, and unknown risk of prolonged exposure to antihypertensive therapies. With newer legislation providing financial incentives for conducting clinical trials in children, along with publication of pediatric-focused guidelines, literature available for antihypertensive agents in pediatrics has increased over the last 20 years. The objective of this article is to review the literature for safety and efficacy of commonly prescribed antihypertensive agents in pediatrics. Thus far, the most data to support use in children was found for angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB). Several gaps were noted in the literature, particularly for beta blockers, vasodilators, and the long-term safety profile of antihypertensive agents in children. Further clinical trials are needed to guide safe and effective prescribing in the pediatric population.

Hypertension in Childhood Nephrotic Syndrome.

Arterial hypertension (HTN) is commonly encountered by clinicians treating children with steroid sensitive (SSNS) and steroid resistant nephrotic syndrome (SRNS). Although the prevalence of HTN in SSNS is less documented than in SRNS, recent studies reported high prevalence in both. Studies have estimated the prevalence of HTN in different patient populations with NS to range from 8 to 59.1%. Ambulatory HTN, abnormalities in BP circadian rhythm, and measures of BP variability are prevalent in patients with NS. Multiple mechanisms and co-morbidities contribute to the pathophysiology of HTN in children with NS. Some contributing factors are known to cause acute and episodic elevations in blood pressure such as fluid shifts, sodium retention, and medication side effects (steroids, CNIs). Others are associated with chronic and more sustained HTN such as renal fibrosis, decreased GFR, and progression of chronic kidney disease. Children with NS are more likely to suffer from other cardiovascular disease risk factors, such as obesity, increased measures of arterial stiffness [increased carotid intima-media thickness (cIMT), endothelial dysfunction, increased pulse wave velocity (PWV)], impaired glucose metabolism, dyslipidemia, left ventricular hypertrophy (LVH), left ventricular dysfunction, and atherosclerosis. Those risk factors have been associated with premature death in adults. In this review on HTN in patients with NS, we will discuss the epidemiology and pathophysiology of hypertension in patients with NS, as well as management aspects of HTN in children with NS.

Case Report: A Child with Gross Hematuria and the Importance of Travel History.

We report a case of a 5-year-old girl who presented with a 3-month-long history of gross hematuria. She underwent an extensive laboratory workup (including an automated urine microscopy) and a kidney biopsy, all of which were within normal limits. While being prepared for a cystoscopy and more advanced imaging of the urinary tract, the family mentioned history of travel to a schistosomiasis endemic area prompting a more thorough ova and parasite examination of the urine. Urine microscopy confirmed the diagnosis of Schistosoma hematobium.

Responsiveness of the PROMIS® measures to changes in disease status among pediatric nephrotic syndrome patients: a Midwest pediatric nephrology consortium study.

BACKGROUND: Nephrotic syndrome represents a condition in pediatric nephrology typified by a relapsing and remitting course, proteinuria and the presence of edema. The PROMIS measures have previously been studied and validated in cross-sectional studies of children with nephrotic syndrome. This study was designed to longitudinally validate the PROMIS measures in pediatric nephrotic syndrome. METHODS: One hundred twenty seven children with nephrotic syndrome between the ages of 8 and 17 years participated in this prospective cohort study. Patients completed a baseline assessment while their nephrotic syndrome was active, a follow-up assessment at the time of their first complete proteinuria remission or study month 3 if no remission occurred, and a final assessment at study month 12. Participants completed six PROMIS measures (Mobility, Fatigue, Pain Interference, Depressive Symptoms, Anxiety, and Peer Relationships), the PedsQL version 4.0, and two global assessment of change items. RESULTS: Disease status was classified at each assessment: nephrotic syndrome active in 100% at baseline, 33% at month 3, and 46% at month 12. The PROMIS domains of Mobility, Fatigue, Pain Interference, Depressive Symptoms, and Anxiety each showed a significant overall improvement over time (p < 0.001). When the PROMIS measures were compared to the patients' global assessment of change, the domains of Mobility, Fatigue, Pain Interference, and Anxiety consistently changed in an expected fashion. With the exception of Pain Interference, change in PROMIS domain scores did not correlate with changes in disease activity. PROMIS domain scores were moderately correlated with analogous PedsQL domain scores. CONCLUSION: This study demonstrates that the PROMIS Mobility, Fatigue, Pain Interference, and Anxiety domains are sensitive to self-reported changes in disease and overall health status over time in children with nephrotic syndrome. The lack of significant anchoring to clinically defined nephrotic syndrome disease active and remission status may highlight an opportunity to improve the measurement of HRQOL in children with nephrotic syndrome through the development of a nephrotic syndrome disease-specific HRQOL measure.

The Microbiome and Blood Pressure: Can Microbes Regulate Our Blood Pressure?

The surfaces of the human body are heavily populated by a highly diverse microbial ecosystem termed the microbiota. The largest and richest among these highly heterogeneous populations of microbes is the gut microbiota. The collection of microbes and their genes, called the microbiome, has been studied intensely through the past few years using novel metagenomics, metatranscriptomics, and metabolomics approaches. This has enhanced our understanding of how the microbiome affects our metabolic, immunologic, neurologic, and endocrine homeostasis. Hypertension is a leading cause of cardiovascular disease worldwide; it contributes to stroke, heart disease, kidney failure, premature death, and disability. Recently, studies in humans and animals have shown that alterations in microbiota and its metabolites are associated with hypertension and atherosclerosis. In this review, we compile the recent findings and hypotheses describing the interplay between the microbiome and blood pressure, and we highlight some prospects by which utilization of microbiome-related techniques may be incorporated to better understand the pathophysiology and treatment of hypertension.

Screening for Hypertension in Children and Adolescents: Methodology and Current Practice Recommendations.

Hypertension (HTN) requires urgent, uniform, and consistent attention across all frontiers of pediatric health care not only because of established links between the onset of HTN during one's youth and its sustenance throughout adulthood but also because of the sequelae associated with the disease's trajectory, such as cardiovascular disease, end organ damage, and decreased quality of life. Although national guidelines for the diagnosis and management of pediatric HTN have been available for nearly 40 years, knowledge and recognition of the problem by clinicians remain poor due to a host of influencing factors. The purpose of this article is to explicate key issues contributing to the inaccurate measurement of blood pressure and misclassification of HTN among children and to present strategies to address these issues.

Gut microbiome and kidney disease: a bidirectional relationship.

Recent technological advances and efforts, including powerful metagenomic and metatranscriptomic analyses, have led to a tremendous growth in our understanding of microbial communities. Changes in microbial abundance or composition of human microbial communities impact human health or disease state. However, explorations into the mechanisms underlying host-microbe interactions in health and disease are still in their infancy. Although changes in the gut microbiota have been described in patients with kidney disease, the relationships between pathogenesis, mechanisms of disease progression, and the gut microbiome are still evolving. Here, we review changes in the host-microbiome symbiotic relationship in an attempt to explore the bidirectional relationship in which alterations in the microbiome affect kidney disease progression and how kidney disease may disrupt a balanced microbiome. We also discuss potential targeted interventions that may help re-establish this symbiosis and propose more effective ways to deploy traditional treatments in patients with kidney disease.

Changes in Urine Microalbumin-to-Creatinine Ratio in Children with Sickle Cell Disease over Time.

BACKGROUND: Approximately 20% of children with sickle cell disease (SCD) have microalbuminuria (MA). Very little is known about the progression of MA in children and young adults with SCD. METHODS: In this study, we analyzed 5-year EMR data of 373 children [with ≥2 microalbumin-to-creatinine (MA/Cr) ratio measurements] followed at the Medical University of South Carolina to determine the rate, direction, magnitude, and predictors of MA/Cr change over time. RESULTS: Age range was 1-22 years; mean 10.2 ± 5.2 years, 49.5% were males. Median follow-up duration was 3.12 ± 1.16 years. At baseline, 328 children had normal (<20 mg/L) MA level. Forty-five (12.1%) of children had MA (≥20 mg/L), of which 91% were ≥8 years and 21 (47%) continued to have MA at the end of the study period. On the other hand, during the study period, 24 new patients developed MA and 24 normalized their MA to levels <20 mg/L. In multivariate logistic regression model, age and bilirubin levels were predictive of MA/Cr increase in patients who received at least one blood transfusion during the study period. Baseline MA level was not predictive of the change in MA/Cr. CONCLUSION: In children and young adults, microalbuminuria is considered a marker of early renal injury. Over time, MA/Cr levels may increase or decrease. Further studies are needed to confirm our findings, assess the reliability of MA as marker of long-term renal injury, and identify high risk patients with SCD likely to have worsening of MA over time.

Incidence, risk factors, and outcomes of opportunistic infections in pediatric renal transplant recipients.

OIs present significant risks to patients following solid organ transplantation. The purpose of this study was to identify risk factors for the development of OIs after kidney transplantation in pediatric patients and to evaluate the impact of OIs on outcomes in this patient population. A single-center retrospective longitudinal cohort analysis including pediatric patients 21 yr of age or younger transplanted from July 1999 to June 2013 at an academic medical center was conducted. Patients were excluded if they received multi-organ transplant. A total of 175 patients were included in the study. Patients who developed OIs were more likely to be female and younger at the time of transplant. A six-factor risk model for OI development was developed. Death, disease recurrence, and PTLD development were similar between groups but trended toward increased incidence in the OI group. Incidence of rejection was significantly higher in the OI group (p = 0.04). Patients who developed OIs had several important risk factors, including younger age, EBV-negative serostatus, CMV donor (+)/recipient (-), biopsy-proven acute rejection, ANC <1000, MMF dose >500 mg/m(2), and any infection. Incidence of rejection was higher in the OI group, but rate of graft loss was not statistically different.

Vitamin D in incident nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Cross-sectional studies of children with prevalent nephrotic syndrome (NS) have shown 25-vitamin D (25(OH)D) deficiency rates of 20-100 %. Information on 25(OH)D status in incident patients or following remission is limited. This study aimed to assess 25(OH)D status of incident idiopathic NS children at presentation and longitudinally with short-term observation. METHODS: Multicenter longitudinal study of children (2-18 years old) from 14 centers across the Midwest Pediatric Nephrology Consortium with incident idiopathic NS. 25(OH)D levels were assessed at diagnosis and 3 months later. RESULTS: Sixty-one children, median age 5 (3, 11) years, completed baseline visit and 51 completed second visit labs. All 61 (100 %) had 25(OH)D < 20 ng/ml at diagnosis. Twenty-seven (53 %) had 25(OH)D < 20 ng/ml at follow-up. Fourteen (28 %) children were steroid resistant. Univariate analysis showed that children prescribed vitamin D supplements were less likely to have 25(OH)D deficiency at follow-up (OR 0.2, 95 % CI 0.04, 0.6). Steroid response, age, and season did not predict 25(OH)D deficiency. Multivariable linear regression modeling showed higher 25(OH)D levels at follow-up by 13.2 ng/ml (SE 4.6, p < 0.01) in children supplemented with vitamin D. CONCLUSIONS: In this incident idiopathic NS cohort, all children at diagnosis had 25(OH)D deficiency and the majority continued to have a deficiency at 2-4 months. Supplemental vitamin D decreased the odds of 25(OH)D deficiency at follow-up, supporting a role for supplementation in incident NS.

Renin Angiotensin System Blocker Fetopathy: A Midwest Pediatric Nephrology Consortium Report.

OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.

Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest Pediatric Nephrology Consortium and the Childhood Arthritis and Rheumatology Research Alliance.

BACKGROUND: There is no clear consensus regarding optimal indications or timing of initial or repeat kidney biopsy in the management of pediatric systemic lupus erythematosus (pSLE). METHODS: A web-based survey was designed to assess current practice patterns among pediatric nephrologists and pediatric rheumatologists and distributed to members of Midwest Pediatric Nephrology Consortium (MWPNC) and Childhood Arthritis and Rheumatology Research Alliance (CARRA). RESULTS: Respondents included 111 rheumatologists and 71 nephrologists from 65 and 34 centers, respectively. Numbers of years in sub-specialty practice were comparable. Rheumatologists and nephrologists frequently collaborate in the care of children with lupus nephritis (LN). More than 90% of respondents refer patients to each either other after diagnosing LN. Over 60% describe shared decision making regarding when to perform kidney biopsy and how to interpret biopsy findings. Many pediatric nephrologists consider biopsy to be of higher risk for complication in pSLE and alter their standard pre-or post-biopsy management. CONCLUSIONS: It is uncommon for pediatric nephrologists to manage LN without input from pediatric rheumatologists and vice versa. Consensus exists between specialties in general, and practice differences that exist occur between individual physicians rather than between specialties. A systematic approach to biopsy may result in improved health related outcomes in pSLE.

The impact of disease duration on quality of life in children with nephrotic syndrome: a Midwest Pediatric Nephrology Consortium study.

BACKGROUND: The Patient Reported Outcomes Measurement Information System (PROMIS) II is a prospective study that evaluates patient reported outcomes in pediatric chronic diseases as a measure of health-related quality of life (HRQOL). We have evaluated the influence of disease duration on HRQOL and, for the first time, compared the findings of the PROMIS measures to those of the PedsQL™ 4.0 Generic Scales (PedsQL) from the PROMIS II nephrotic syndrome (NS) longitudinal cohort. METHODS: This was a prospective study in which 127 children (age range 8-17 years) with active NS from 14 centers were enrolled. Children with active NS defined as the presence of nephrotic range proteinuria (>2+ urinalysis and edema or urine protein/creatinine ratio >2 g/g) were eligible. Comparisons were made between children with prevalent (N = 67) and incident (N = 60) disease at the study enrollment visit. RESULTS: The PROMIS scores were worse in prevalent patients in the domains of peer relationship (p = 0.01) and pain interference (p < 0.01). The PedsQL showed worse scores in prevalent patients for social functioning (p < 0.01) and school functioning (p = 0.03). Multivariable analyses showed that prevalent patients had worse scores in PROMIS pain interference (p = 0.02) and PedsQL social functioning (p < 0.01). CONCLUSION: The PROMIS measures detected a significant impact of disease duration on HRQOL in children, such that peer relationships were worse and pain interfered with daily life to a greater degree among those with longer disease duration. These findings were in agreement with those for similar domains in the PedsQL legacy instrument.

Decreased heart rate variability is associated with increased transcranial Doppler velocities in children with sickle cell disease.

OBJECTIVE: To explore the relationship between 24-hour blood pressure (BP) variability, heart rate (HR) variability, and transcranial Doppler velocity (TCDV) in a cohort of pediatric sickle cell disease (SCD) patients. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective study of 11 children aged 8-18 years with SCD who previously underwent 24-hour ambulatory BP monitoring and TCDV measurements. INTERVENTIONS: Medical records were reviewed for TCDV and 24-hour ABP data. TCDV in the right and left middle cerebral artery were examined, and the highest velocity was recorded. HR and BP standard deviations were used as markers of variability. The relationships between daytime, nighttime, and 24-hour blood pressures and heart rate variability were determined. RESULTS: Mean age, body mass index and hemoglobin levels were 11.2 ± 3.0 years, 18.7 ± 3.4 kg/m2, and 9.1 ± 1.7 g/dL, respectively. Median transcranial Doppler velocity was 136cm/s (125-142). Decreased day, night, and 24-hour heart rate variability were significantly associated with increased transcranial Doppler velocity (R = -.69, P = .02; R = -.82 P =.002; R = -.66, P = .03, respectively). BP variability did not correlate with TCDV. Nighttime BP indexes were higher than daytime. CONCLUSIONS: In this small cohort, decreased heart rate variability assessed by the standard deviation of HR was associated with increased transcranial Doppler velocities in children with SCD. No correlation between measurements of BP variability and TCDV was found. Our study provides new information on heart rate and blood pressure variability and TCDV; a surrogate marker of stroke risk in sickle cell disease. Larger multicenter studies are needed to confirm our findings.

Blood Pressure, Heart Rate, and CNS Stimulant Medication Use in Children with and without ADHD: Analysis of NHANES Data.

It is estimated that 2-3% of children in the US have hypertension (HTN) and 8% of children ages 4-17 carry the diagnosis of attention-deficit hyperactivity disorder (ADHD). The prevalence of HTN and cardiovascular (CV) risk factors in children with ADHD on CNS stimulant treatment (stimulants) compared to no treatment and compared to their healthy counterparts is not well described. Using National Health and Nutrition Survey data, we examined demographic, blood pressure (BP) and CV risk factors of 4,907 children aged 12-18 years with and without the diagnosis of ADHD, and further examined the CV risk in a subgroup of ADHD patients on stimulants. Three hundred eighty-three (10.7%) children were reported to have ADHD, of whom 111 (3.4%) were on stimulants. Children with ADHD on stimulants were significantly younger, male, and white compared to those with ADHD not on medication and those without ADHD. Body mass index (BMI), eGFR, cholesterol, the prevalence of albuminuria, and poverty were not significantly different between the three groups. One hundred sixty (2.7%) had BP in the hypertensive and 637 (12.4%) in the pre-hypertensive range. The prevalence of elevated BP (HTN and/or pre-HTN range) was not different between children with ADHD on stimulants compared to ADHD without medication and those without ADHD. Heart rate (HR) was significantly higher in the ADHD group on stimulants vs. the groups ADHD on no stimulants and without ADHD. When the relationship between stimulants and the risk of abnormal BP was examined, there was a significant interaction between having BP in the HTN range and sex. After adjusting for BMI, race, and age, females with ADHD on stimulants tended to be older and had significantly more BP in the hypertensive range. On the other hand, males were more likely to be of a white race and older, but not hypertensive. Children with ADHD on stimulants have significantly higher HR than children with ADHD on no stimulants and children without ADHD. On the other hand, the prevalence of abnormal BP classification is comparable between the three groups.