Edited by: Ibrahim F. Shatat, Medical University of South Carolina, USA
Reviewed by: Tammy Brady, Johns Hopkins University, USA; Donald Lee Batisky, Emory University, USA
Specialty section: This article was submitted to Pediatric Nephrology, a section of the journal Frontiers in Pediatrics
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Hyponatremic hypertensive syndrome (HHS) is an uncommon disorder usually encountered in the adult population with unilateral renal artery stenosis and is under-recognized in the pediatric population.
A 19-month-old male presented with new-onset status epilepticus associated with neurological sequelae, and hypertension to a high of 248/150 mmHg. Lab work revealed significant hyponatremia, elevated peripheral renin activity, and increase in aldosterone and ADH levels. A diagnosis of HHS was made. Initial analysis revealed a high-grade proximal renal artery stenosis by magnetic resonance imaging (MRI) and angiogram. Electroencephalogram and an MRI of the brain demonstrated characteristic abnormalities of the left temporal–parietal regions consistent with posterior reversible leukoencephalopathy syndrome (PRES). The patient responded to right renal artery balloon dilation and stent placement. Since intervention and close blood pressure control with Amlodipine, the patient has been free of seizures and is neurologically intact.
We report a case of malignant hypertension in a 19-month-old male secondary to renal artery stenosis with associated HHS and PRES. Prognosis of PRES in children with renal disease is excellent. Prompt intervention may offer near complete resolution of physiologic and symptomatic effects of HHS and PRES due to high-grade renal artery stenosis. This report was written with parental consent for de-identified case presentation and radiographs for the educational benefit of other medical professionals.
Renovascular disease is responsible for approximately 5–25% of all childhood hypertension (
Renal artery stenosis may result in critical renal ischemia, leading to renin hypersecretion. Elevated downstream modulators such as angiotensin II and aldosterone potentiate hemodynamic changes, resulting in hypertension and pressure natriuresis. Malignant hypertension on presentation is well reported in adults with HHS, though reports in children are slowly emerging (
A 19-month-old African American male was transferred from an outside hospital to our pediatric unit for new-onset status epilepticus and hyponatremia (serum sodium of 126 mmol/L). He initially presented with generalized tonic–clonic seizures unresponsive to rectal Diazepam, but eventually resolved with intravenous Lorazepam after approximately 15 min. Upon admission, the patient appeared lethargic but responsive. Vital signs on admission: blood pressure 218/144, heart rate of 210, respiratory rate was 32, and temperature was 36.8°C. Lab work revealed hyponatremia, an elevated peripheral renin activity, aldosterone and ADH levels, and a normal serum creatinine (Table
Chemistries | Serum | Reference values | Spot urine | Reference values |
---|---|---|---|---|
Osmolality | 273 | 280–295 mOsm/Kg | 329 |
500–800 mOsm/Kg |
Sodium | 128 |
135–148 mmol/L | 18 | >20 mmol/L |
Potassium | 3.2 | 3.5–5.3 mmol/L | 38.5 | 10–60 mmol/L |
Chloride | 87 | 98–108 mmol/L | 22 | mmol/L |
Bicarbonate | 24 | 21–31 mmol/L | ||
Glucose | 89 | 70–99 mg/dL | ||
BUN | 14 | 5–20 mg/dL | ||
Creatinine | 0.35 | 0.50–1.20 mg/dL | ||
Calcium | 9.9 | 8.6–10.2 mg/dL | ||
Phosphorus | 5.9 | 4.5–6.7 mg/dL | ||
Magnesium | 2.3 | 1.6–2.6 mg/dL | ||
Aldosterone | 743 |
7–93 ng/dL | ||
ADH | 64.6 |
<0.69 ng/dL | ||
Peripheral renin activity | 137 |
3–11 ng/ml/min |
Electrocardiogram (ECG) showed sinus tachycardia and a waveform characteristic concerning for left ventricular hypertrophy. Echocardiogram demonstrated normal biventricular size with qualitatively mild concentric left ventricular hypertrophy.
Upon review of systems, the family revealed a 1 kg weight loss over the course of 10 days. He was seen by a pediatric gastroenterologist for daily non-bloody, non-bilious emesis, and was treated for gastroesophageal reflux disease (GERD). During this time, he also demonstrated signs of polyuria and polydipsia with water intake increasing to 8–10 bottle per day.
Shortly after admission, his blood pressure increased to 248/150 mmHg. He became lethargic and suffered a second episode of seizure activity, which was successfully treated with Lorazepam followed by a loading dose of Phenobarbital. His blood pressure was titrated with a nicardipine infusion for a target range of 120–140 mmHg systolic and 70–80 mmHg diastolic.
A renal ultrasound revealed a smaller right kidney (length 6.4 cm) as compared to the left (length 7.6 cm). The right kidney when compared to the left had less cortical thickness and increased echogenicity suggestive of vascular insult. The vessels were not completely visualized via color Doppler.
MRI of the brain without contrast demonstrated features consistent with PRES (Figure
The right renal artery was balloon dilated to 50% as shown in Figure
HTN in children is more likely due to a secondary cause if the BP is elevated to greater than the age-sex-height specific 99th ‰ + 5 mmHg (Stage 2 HTN range) or if the child is young at presentation. Renal etiologies explain many secondary causes, with renovascular hypertension one of the most common renal forms of secondary HTN. Renovascular hypertension should be suspected in children with suspected secondary HTN, as well as in those with raised peripheral plasma renin, moderate hypokalemia, or HTN so severe that it requires more than two agents to normalize the BP (
Categories | Specific etiologies |
---|---|
Anatomical | Fibromuscular dysplasia, extrinsic compression |
Vasculitis | Kawasaki disease, polyarteritis nodosa, Takayasu’s disease |
Syndromes | Neurofibromatosis 1, tuberous sclerosis, Marfan’s syndrome, William’s syndrome |
Localized tissue damage | Trauma, radiation, umbilical artery catheterization |
Congenital | Congenital rubella |
Presenting symptoms of HHS include central nervous system (CNS) abnormalities such as headache, confusion, and most importantly seizures as in this case, along with other neuro-behavioral complaints, weight loss, polydipsia, and polyuria (
Posterior reversible leukoencephalopathy syndrome is underreported in children and thus far has only been described in cases in which the primary diagnoses are glomerulonephritis, systemic lupus erythematosus, Henoch–Schönlein purpura/nephritis, hemolytic uremic syndrome, or hematologic/oncologic diagnoses (
The pathophysiology of PRES secondary to HTN is thought to be due to reduced cerebral blood flow and capillary leakage with endothelial dysfunction leading to hypoperfusion and ischemia. The posterior region of the brain is more susceptible to ischemic pathology due to its impaired autoregulation and decreased sympathetic innervation. HTN, however, is not present in 20–40% of cases and the pathophysiology of other etiologies is not well understood (
The mainstay of treatment for HHS and PRES in the setting of renovascular disease is to first decrease the blood pressure while replacing fluid losses. Management ultimately depends on the underlying cause of hypertensive disease; in this case, renovascular disease (
Studies have shown high success rates of revascularization procedures in patients with fibromuscular dysplasia or mid-aortic syndrome in comparison to those who have diffuse abnormalities of small infrarenal arteries (
The prognosis of PRES in children with renal disease, such as our patient, is excellent and most patients recover within a few weeks with minimal neurological sequelae (
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.