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Author(s): Cailin E. Kellum [sup.1] , Keri M. Kemp [sup.1] , Sylvie Mrug [sup.3] , Jennifer S. Pollock [sup.1] , Michael E. Seifert [sup.2] , Daniel I. Feig [sup.2] Author [...], Background Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, are associated with a higher risk of cardiovascular disease (CVD) and indicators of future CVD risk in adulthood, such as greater vascular stiffness. The impact of ACEs in adolescence is unclear, and understanding how ACEs relate to blood pressure (BP) and vascular function during early life is key for the development of prevention strategies to reduce CVD risk. We hypothesized that exposure to ACEs would be associated with changes in central hemodynamics such as increased vascular stiffness and higher BP during adolescence. Methods This pilot study enrolled 86 adolescents recruited from the Children's of Alabama. A validated ACE questionnaire was employed, and ACEs were modeled both as a continuous variable and a categorical variable (ACE [greater than or equal to] 1 vs. ACE = 0). The primary outcomes used are considered to be indicators of future cardio-renal disease risk: aortic augmentation index normalized to 75 bpm (Alx75, a surrogate for vascular stiffness), carotid-femoral PWV (m/s), and ambulatory BP patterns. Results Adolescents with ACE [greater than or equal to] 1 had significantly higher Alx75 (ACE: 5.2% ± 2.2 compared to no ACE: - 1.4% ± 3.0; p = 0.043). PWV only reflected this trend when adjustments were made for the body mass index. Adolescents with ACEs showed no differences in ambulatory BP patterns during the 24-h, wake, or sleep periods compared to adolescents with no ACEs. Conclusions ACEs were associated with higher AIx75 in adolescence, which is a risk factor for future CVD. Adolescence could present an opportunity for early detections/interventions to mitigate adverse cardiovascular outcomes in adulthood. Graphical abstract

Author(s): Erica C. Bjornstad [sup.1] , Michael E. Seifert [sup.1] , Keia Sanderson [sup.2] , Daniel I. Feig [sup.1] Author Affiliations: (1) grid.265892.2, 0000000106344187, Department of Pediatrics, Nephrology, University of [...], Research indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection can impact every organ, and the effects can range from asymptomatic to severe disease. Since it was first discovered in December 2019, our understanding has grown about its impact on kidney disease. In general, children have less severe disease than adults, and this tendency appears to extend to special pediatric kidney populations (e.g., chronic kidney disease and immunosuppressed patients with solid organ transplants or nephrotic syndrome). However, in a fraction of infected children, SARS-CoV2 causes an array of kidney manifestations, ranging from acute kidney injury to thrombotic microangiopathy, with potential implications for increased risk of morbidity and mortality. Additional considerations surround the propensity for clotting extracorporeal circuits in children with SARS-CoV2 infection that are receiving kidney replacement therapy. This review provides an update on our current understanding of SARS-CoV2 for pediatric nephrologists and highlights knowledge gaps to be addressed by future research during this ongoing pandemic, particularly the social disparities magnified during this period.

Author(s): Jeffrey D. Lebensburger [sup.1] , Gary R. Cutter [sup.2] , Thomas H. Howard [sup.1] , Paul Muntner [sup.3] , Daniel I. Feig [sup.4] Author Affiliations: (1) Pediatric Hematology and [...], Background Patients with sickle cell anemia (SCA) have an increased prevalence of nephropathy and mortality from chronic kidney disease (CKD). Methods We evaluated the association of hyperuricemia and nocturnal hypertension with lower estimated glomerular filtration rate (eGFR) using cystatin-C in patients aged 10-21 years with the HbSS or HbSB0 form of the disease during a non-acute clinic visit. eGFR and uric acid measurements were obtained in 83 and 81 participants, respectively, and 24-h ambulatory blood pressure monitoring (ABPM) was performed in 44 participants. Annual testing included vital signs, complete blood count, comprehensive metabolic panel, medications, urine microalbumin/creatinine, and lactate dehydrogenase measurements. Hyperuricemia was defined as a uric acid level of [greater than or equal to]5.5 mg/dL. Nocturnal hypertension was defined as >25% of nocturnal readings at >95th percentile according to norms established by the American Heart Association Statement on ABPM in children and adolescents. Results The mean eGFR was statistically significantly lower in patients with hyperuricemia than in those with normal uric acid levels (143 vs. 161 mL/min/1.73 m.sup.2, respectively). Of the 44 participants for whom ABPM data were available, 14 (32%) had systolic nocturnal hypertension and 12 (27%) had diastolic nocturnal hypertension. The mean eGFR was statistically significantly lower in participants with nocturnal systolic and diastolic hypertension than in those with normal nocturnal blood pressure. In a regression model, nocturnal hypertension and hyperuricemia were associated with a lower eGFR. Conclusions Two risk factors for CKD, i.e., nocturnal hypertension and hyperuricemia, were associated with lower eGFR in older children and adolescent patients with SCA. Long-term studies on their association with progression to CKD in this population are warranted. Key point Nocturnal hypertension and hyperuricemia are established risk factors for nephropathy in other diseases and may play a role in SCA nephropathy.

Author(s): Jeffrey D. Lebensburger[sup.1] , Prasannalaxmi Palabindela[sup.1] , Thomas H. Howard[sup.1] , Daniel I. Feig[sup.2] , Inmaculada Aban[sup.3] , David J. Askenazi[sup.2] Author Affiliations: (1) Pediatric Hematology Oncology, University of [...], Background Patients with sickle cell disease are at risk for developing chronic kidney disease (CKD). Acute kidney injury (AKI) has been linked to progression to CKD, but limited data exist to determine its role in acute complications of sickle cell disease. We hypothesized that AKI occurs in pediatric patients admitted for acute chest syndrome (ACS) and prolongs hospitalization. Methods We conducted a 6-year retrospective review of pediatric patients with ACS admitted to a single medical institution. Results Of the 149 pediatric patients admitted for ACS during the 6-year study period, 12 (8 %) developed AKI. Comparison of patients with and without AKI revealed a significant association between AKI and a larger drop in hemoglobin value from baseline (2.7 vs. 1.4 g/dL; p = 0.003), a lower hemoglobin value at admission (6.4 vs. 7.5 g/dL; p = 0.03), and an increased white blood cell count at admission (33.1 vs. 19.8 x 10.sup.9/L; p < 0.0001), respectively. AKI (p < 0.0001) together with need for advanced respiratory support (biphasic positive airway pressure or mechanical ventilation) (p < 0.0001) and need for exchange transfusion (p < 0.0001) were associated with prolonged hospitalization. Conclusions Clinicians should monitor pediatric patients hospitalized for ACS for the development of AKI as a potentially modifiable risk factor for prolonged hospitalization.

Introduction Left ventricular mass index (LVMI), an allometrically corrected echocardiographic measure, has been used to quantify hypertension-induced left ventricular hypertrophy (LVH) and predict cardiovascular mortality in adults[1-5]. While a LVMI [...], Background Left ventricular mass index (LVMI) is a surrogate of left ventricular hypertrophy and a predictor of cardiac morbidity and mortality in adults with hypertension. LVMI has not been linked to cardiovascular endpoints in children. The aim of this study was to identify an association between elevated LVMI and echocardiographic markers of systolic and diastolic function. Methods The study was a retrospective review of chronic dialysis patients from June 1995 to December 2009 at a single tertiary care children&apos;s hospital. The upper limit cutoffs for LVMI were set at >38.6 g/[m.sup.2.7], >51 g/[m.sup.2.7], and by age and sex-based normative values. Sixty-three patients (mean age 14.1 years, 56% males) were enrolled in the study, with a total of 287 echocardiograms. Results Post-dialysis hypertension was associated with elevated LVMI in both the >51 g/[m.sup.2.7] [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.5-5.5] and normative (OR 3.4, 95% CI 1.5-7.7) models. Elevated LVMI, when defined by the >51 g/[m.sup.2.7] and normative models, was significantly associated with decreased shortening fraction (OR 4.1, 95% CI 1.7-9.8 and OR 5.4, 95% CI 1.3-22.9, respectively) and increased mitral E wave to lateral mitral tissue Doppler e&apos; wave velocity ratio (E/e&apos;; OR 3.5, 95% CI 1.1-11.2 and OR 4.5, 95% CI 1.0-21.6, respectively). Conclusions Elevated LVMI is associated with decreased systolic and diastolic cardiac function, justifying its use as a surrogate of hypertensive cardiomyopathy in children undergoing chronic dialysis. Keywords Left ventricular mass index * Dialysis * Hypertension * Diastolic dysfunction * Systolic dysfunction

Author(s): Douglas M. Silverstein [sup.1] , Poyyapkam R. Srivaths [sup.2] , Parnell Mattison [sup.1] , Kiran Upadhyay [sup.1] , Laurie Midgley [sup.1] , Asha Moudgil [sup.1] , Stuart L. Goldstein [...], Serum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients. UA levels were similar in both groups [6.8 ± 0.2 (HD) vs. 6.5 ± 0.3 (PD), p = 0.6]. Pre-treatment systolic BP percentile was associated with a high UA level [91.9 ± 2.3 (>6.0 mg/dL) vs. 79.3 ± 5.8 mm Hg ([less than or equal to]6.0 mg/dL), p = 0.01] in HD patients only. There was a negative relationship between UA and dialysis vintage (r = -0.31, p = 0.01). In both groups, there was no relationship between UA and Kt/V. In HD patients, fluid overload was unrelated to UA level [4.2 ± 0.6% ([less than or equal to]6.0 mg/dL) vs. 4.3 ± 0.3% (>6.0 mg/dL), p = 0.9]. Moreover, pre-HD treatment systolic BP percentile correlated with UA (beta 0.36, p = 0.02) independent of volume. UA levels were higher in patients receiving anti-hypertensive medications [6.3 ± 0.2 (No Meds] vs 7.0 ± 0.2 (BP Meds) mg/dL, p= 0.01]. Finally, there was no relationship between serum UA and normalized protein catabolic rate (r = 0.14; p = 0.4). In summary, serum UA impacts BP in pediatric HD patients, independent of volume, nutritional and weight status.

Introduction Over the last decade, results from animal models, epidemiological studies and clinical trials have suggested a causal role of serum uric acid (UA) in the development of vascular disease [...], Serum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients. UA levels were similar in both groups [6.8 [+ or -] 0.2 (HD) vs. 6.5 [+ or -] 0.3 (PD), p= 0.6]. Pre-treatment systolic BP percentile was associated with a high UA level [91.9 [+ or -] 2.3 (>6.0 mg/dL) vs. 79.3 [+ or -] 5.8 mm Hg ([less than or equal to] 6.0 mg/dL), p=0.01] in HD patients only. There was a negative relationship between UA and dialysis vintage (r=-0.31, p=0.01). In both groups, there was no relationship between UA and Kt/V. In HD patients, fluid overload was unrelated to UA level [4.2 [+ or -] 0.6% ([less than or equal to] 6.0 mg/dL) vs. 4.3 [+ or -] 0.3% (>6.0 mg/dL), p=0.9]. Moreover, pre-HD treatment systolic BP percentile correlated with UA (beta 0.36, p=0.02) independent of volume. UA levels were higher in patients receiving anti-hypertensive medications [6.3 [+ or -] 0.2 (No Meds] vs 7.0 [+ or -] 0.2 (BP Meds) mg/dL, p=0.01]. Finally, there was no relationship between serum UA and normalized protein catabolic rate (r=0.14; p=0.4). In summary, serum UA impacts BP in pediatric HD patients, independent of volume, nutritional and weight status. Keywords Uric acid * Hypertension * End-stage renal disease

The article discusses several studies relating to uric acid and its link to an increased risk of cardiovascular disease, hypertension and renal disease. It highlights the need for further testing to actually prove the connection between excessive uric acid and an increased risk of cardiovascular disease.

A study was conducted to determine whether lowering uric acid results in lowering blood pressure (BP) amongst hyperuricemic adolescents who have recently been diagnosed with hypertension. Results revealed that treatment with allopurinol resulted in reduced BP and suggest further research.

Byline: Beth Croix (1), Daniel I. Feig (1,2) Keywords: Hypertension; Children; Adolescents; Clinical research; Retrospective study Abstract: Early hypertension has generally been considered to be an asymptomatic condition however, recent data show that many hypertensive children have evidence of end organ damage. We sought to determine if a spectrum of common symptoms is associated with early hypertension and whether those symptoms resolve with lowered blood pressure. Four hundred and nine consecutive children, 7--18 years old, examined in the Texas Children&apos;s Hospital Hypertension Clinic for new-onset high blood pressure (BP) completed a questionnaire, including the self-reporting of 15 symptoms potentially attributed to high blood pressure. Subjects received anti-hypertensive treatment and repeated the questionnaire 4--6 months after initiation of therapy. One-hundred fifty healthy, normotensive children completed the questionnaire as controls. Of hypertensive children, 64% were symptomatic, compared with 26% of normotensive children (P&lt 0.001). Fifty-one percent of hypertensive children reported 1--4 symptoms, 14% &gt 4 symptoms. Following treatment only 28% of children remained symptomatic. The three most common symptoms in hypertensive patients, headache, 42%, difficulty initiating sleep, 27%, and daytime tiredness, 26%, were markedly reduced with treatment, to 6.2%, 1.5% and 10%, respectively (P&lt 0.001). We conclude that newly diagnosed hypertensive children had a variety of non-specific symptoms, more prevalent than those of normotensive children, and most somatic complaints improved with 4--6 months of anti-hypertensive treatment. Author Affiliation: (1) Renal Section, Department of Pediatrics, Baylor College of Medicine and Texas Children&apos;s Hospital, Houston, TX, USA (2) Pediatric Hypertension Clinics Renal Section, Department of Pediatrics, MC3-2482, Baylor College of Medicine, 1102 Bates Street, Houston, TX, 77030, USA Article History: Registration Date: 10/01/2006 Received Date: 12/08/2005 Accepted Date: 12/10/2005 Online Date: 21/02/2006

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid. obesity; insulin resistance

Because of its availability, carbamazepine is a drug commonly involved in accidental and intentional overdoses. Carbamazepine, approved by the Food and Drug Administration in 1968, is indicated as first-line therapy [...], Carbamazepine intoxication is common in the pediatric population. Highly protein-bound, carbamazepine is not removed efficiently through conventional hemodialysis. We describe the use of albumin-enhanced continuous venovenous hemodialysis (CVVHD) in a 10-year-old girl who developed coma and respiratory depression due to an intentional carbamazepine overdose (peak drug level of 44.8 µg/ml; therapeutic range: 8-12 µg/ml). Without intervention, the half-life of drug elimination is 25 to 60 hours in patients who are naive to carbamazepine and 12 to 20 hours in children on chronic carbamazepine therapy. In contrast, with albumin-enhanced CVVHD, we observed a half-life of 7 to 8 hours. The patient recovered rapidly and was discharged from hospital

Reverse-phase and anion-exchange HPLC, which help recognize significant mutagenic lesions that exist in nucleotides modified oxidatively, isolate a 5-hydroxy-2'-deoxycytidine lesion. The oxidative, highly-mutagenic DNA lesion induces C to T transformation in Escherichia coli. The process helps identify the chemical identities of DNA lesions and is called reverse chemical mutagenesis.

OBJECTIVE. Hypertension is common in the pediatric population. There is increasing evidence for early hypertensive target organ damage that may lead to substantial long-term morbidity. Because a critical aspect of [...]