Hypertension and blood pressure variability (BPV; SD and average real variability) in primary proteinuric glomerulopathies are not well described. Data were from 433 participants in the NEPTUNE ...(Nephrotic Syndrome Study Network). Hypertensive BP status was defined as previous history of hypertension or BP ≥140/90 mm Hg for adults/≥95th percentile for children at baseline. BPV was measured in participants with ≥3 visits in the first year. Two-hundred ninety-six adults (43 years interquartile range, 32-57.8 years, 61.5% male) and 147 children (11 years interquartile range, 5-14 years, 57.8% male) were evaluated. At baseline, 64.8% of adults and 46.9% of children were hypertensive. Histological diagnosis was associated with hypertensive status in adults (
=0.036). In adults, hypertensive status was associated with lower hazard of complete remission (hazard ratio, 0.36; 95% confidence interval, 0.19-0.68) and greater hazard of achieving the composite end point (end-stage renal disease or estimated glomerular filtration rate decline >40%; hazard ratio, 4.1; 95% confidence interval, 1.4-12). Greater systolic and diastolic SD and average real variability were also associated with greater hazard of reaching the composite end point in adults (all
<0.01). In children, greater BPV was an independent predictor of composite end point (determined by systolic SD and average real variability) and complete remission (determined by systolic and diastolic average real variability; all
<0.05). Hypertensive status was common among adults and children enrolled in NEPTUNE. Differences in hypertensive status prevalence, BPV, and treatment were found by age and histological diagnosis. In addition, hypertensive status and greater BPV were associated with poorer clinical outcomes.
Pediatric solid-organ transplantation is an increasingly successful treatment for solid-organ failure. With dramatic improvements in patient survival rates over the last several decades, there has ...been a corresponding emergence of complications attributable to pretransplant factors, transplantation itself, and the management of transplantation with effective immunosuppression. The predominant solid-organ transplantation sequelae are medical and psychosocial. These sequelae have a substantial effect on transition to adult care; as such, hurdles to successful transition of care arise from the patients, their families, and pediatric and adult health care providers. Crucial to successful transitioning is the ongoing development of a sense of autonomy and responsibility for one's own care. In this article we address the barriers to transitioning that occur with long-term survival in pediatric solid-organ transplantation. Although a particular transitioning model is not promoted, practical tools and strategies that contribute to successful transitioning of pediatric patients who have received a transplant are suggested.
The endothelin (ET) system seems to play a pivotal role in hypertension and in proteinuric kidney disease, including the micro- and macro-vascular complications of diabetes. Endothelin-1 (ET-1) is a ...multifunctional peptide that primarily acts as a potent vasoconstrictor with direct effects on systemic vasculature and the kidney. ET-1 and ET receptors are expressed in the vascular smooth muscle cells, endothelial cells, fibroblasts and macrophages in systemic vasculature and arterioles of the kidney, and are associated with collagen accumulation, inflammation, extracellular matrix remodeling, and renal fibrosis. Experimental evidence and recent clinical studies suggest that endothelin receptor blockade, in particular selective ET
A
R blockade, holds promise in the treatment of hypertension, proteinuria, and diabetes. Concomitant blockade of the ET
B
receptor is not usually beneficial and may lead to vasoconstriction and salt and water retention. The side-effect profile of ET receptor antagonists and relatively poor antagonist selectivity for ET
A
receptor are limitations that need to be addressed. This review will discuss what is currently known about the endothelin system, the role of ET-1 in the pathogenesis of hypertension and kidney disease, and summarize literature on the therapeutic potential of endothelin system antagonism.
Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of ...immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio‐emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers’ perspectives, in predicting medication non‐adherence for adolescents (ages 12‐19 years) 1 year post‐transplant. Non‐adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers’ perceptions of poorer overall family functioning predicted missed medication doses (ΔR2 = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem‐solving (β = −0.795, t(21) = −2.927, P = 0.008) and affective involvement (β = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR2 = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family‐based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.
Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few ...data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m
Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.
Abstract
Context:
The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of ...1,25-dihydroxyvitamin D3 with consequent hypercalcemia and hypercalciuria and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low-calcium diet, reduced dietary vitamin D intake, and limited sunlight exposure. CYP3A4 is a P450 enzyme that inactivates many drugs and xenobiotics and may represent an alternative pathway for inactivation of vitamin D metabolites.
Objective:
Our goal was to determine if rifampin, a potent inducer of CYP3A4, can normalize mineral metabolism in patients with IIH due to mutations in CYP24A1.
Methods:
We treated two patients with IIH with daily rifampin (10 mg/kg/d, up to a maximum of 600 mg). Serum calcium, phosphorus, parathyroid hormone (PTH), liver, and adrenal function and vitamin D metabolites, as well as urinary calcium excretion, were monitored during treatment of up to 13 months.
Results:
Prior to treatment, both patients had hypercalcemia, hypercalciuria, and nephrocalcinosis with elevated serum 1,25-dihydroxyvitamin D3 and suppressed serum PTH. Daily treatment with rifampin was well tolerated and led to normalization or improvement in all clinical and biochemical parameters.
Conclusion:
These observations suggest that rifampin-induced overexpression of CYP3A4 provides an alternative pathway for inactivation of vitamin D metabolites in patients who lack CYP24A1 function.
Two patients with biallelic CYP24A1 mutations and intractable hypercalcemia were treated with rifampin for up to 13 months. CYP3A4 induction by rifampin resulted in normalization of mineral metabolism.
Purpose of Review
Turner syndrome (TS), neurofibromatosis type 1(NF1), and William Syndrome (WS) are 3 genetic conditions that are all associated with a substantial increase in risk of hypertension. ...In this review, we focus on factors leading to hypertension and on clinical manifestations and management of hypertension in children and adolescents with these genetic conditions
Recent Findings
In most instances, hypertension is secondary. There is a high prevalence of masked hypertension in TS; however, the extent to which control of the BP helps reduce the risk of aortic dissection/aneurysm in TS is not yet fully elucidated. Vasculopathies are the least emphasized but most important manifestation of NF1. Of note, routine screening for pheochromocytoma in NFI is not recommended as it is not cost-effective. Cardiovascular complications are the major cause of death in patients with WBS. ABPM identifies patients without overt aortic or renovascular narrowing. Antihypertensive agents such as ARBs that have direct vascular wall effects and agents that inhibit oxidative stress (minoxidil) should be considered, even in those who do not exhibit overt hypertension. Elevated blood pressure in children and adolescence manifests early with end-organ changes and when left untreated, increases risk for premature onset of cardiovascular disease.
Summary
Vigilant monitoring of the blood pressure is recommended. Accurate early diagnosis and management of hypertension will delay or prevent target organ damage and ensure a healthier transition to adulthood among children afflicted with these conditions.
Background
Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that in children unlike in adults shows no sex predilection. FMD is often underdiagnosed, and its pathophysiology is ...unclear. Delayed diagnosis may lead to refractory hypertension and decreases the chance of successful treatment. Doppler ultrasound (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and catheter-based angiography (angiography) are currently used to help make a clinicoradiological diagnosis of FMD. The main aim of the study was to compare the efficacy of imaging modalities which can allow for earlier and improved detection. Furthermore, an anatomical mapping of the location of lesions can help determine the best treatment modalities.
Methods
All patients with non-syndromic non-inflammatory renovascular hypertension were recruited from the Nephrology Department at the Children’s Hospital of Philadelphia (CHOP) and enrolled in the U.S. FMD Registry maintained at the University of Michigan. Clinical presentation and imaging findings on US, CT, and MRI of children diagnosed with FMD were evaluated.
Results
Mean age at diagnosis was 7 ± 4.9 years (4 months–17 years). Family history of hypertension (HTN) (52%), FMD (8.7%), Caucasian (60%), headache (48%), and HTN (80%) were the most prevalent symptom and sign at presentation. Bruits were 100% specific for renal artery stenosis (RAS) diagnosis but were heard in the minority of patients (3 patients, 12%). FMD was mainly unifocal within a single site (68%) or multiple sites (28%) and involved the main or first order renal branch in about 68% of children. Isolated distal lesions beyond the second order branches were found in about 25% of children. US imaging was significantly less sensitive than angiography (28%,
p
= 0.003). MRA had a better sensitivity (62.5%,
p
= 0.3) than US. Overall, CTA had the best sensitivity (84.2%,
p
= 0.4) compared to angiography; however, only angiography showed distal vessel disease.
Conclusions
Limitations of the study include the sample size and biases—only patients diagnosed with FMD were included in this study and most patients were referred to a pediatric nephrologist for unexplained hypertension. Angiography should be performed as part of the initial work-up of any child suspected of having renovascular FMD, regardless of the findings seen on US, MRA, or CTA.
Idiopathic mid-aortic syndrome in children Sethna, Christine B.; Kaplan, Bernard S.; Cahill, Anne Marie ...
Pediatric nephrology (Berlin, West),
07/2008, Volume:
23, Issue:
7
Journal Article
Peer reviewed
Mid-aortic syndrome (MAS) is an uncommon condition characterized by narrowing of the abdominal aorta and stenosis of its major branches. Our goal was to illustrate the presentation, diagnosis and ...management of six new cases of idiopathic MAS together with 96 cases of idiopathic MAS from the literature. The mean age of the 102 cases was 14.3 years (19 days to 49 years). Our patient who presented at 19 days of age is the youngest reported to date. Clinical presentations included hypertension (94%), claudication (17%), renal failure (4%) and intestinal ischemia (1%). Angiography was the diagnostic imaging study of choice. Renal arteries were involved in 91% of patients, while the superior mesenteric artery and celiac artery were involved in 35%. Thirteen percent of cases were managed medically, and the remainder was treated surgically. Our experience shows that initial conservative blood pressure management of idiopathic MAS is feasible unless medical control of hypertension is unsatisfactory, renal function is at risk or there are symptoms of claudication or intestinal ischemia. Careful timing and planning of a surgical intervention is possible for most cases and may, in select cases, be considered after completion of puberty to allow growth to be completed.
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