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A 3-year-old girl presented to the emergency department with seizures, low-grade fever and vomiting. She had tachycardia and a slow capillary refill. Blood pressure could not be measured. Because of suspected sepsis and/or meningo-encephalitis, broad spectrum antibiotics and antiviral medication were given together, along with volume expansion and anticonvulsive therapy. A few hours later, after a second seizure, the blood pressure was extremely high (156/116 mm Hg). The girl was treated with anticonvulsants and intravenous antihypertensive agents. MRI of the brain showed signs of posterior reversible encephalopathy syndrome. Cultures of blood and cerebrospinal fluid remained sterile. Further investigation into the cause of the malignant hypertension revealed hypokalemia, metabolic alkalosis and extremely high plasma renin activity, caused by a rare renal abnormality: bilateral renal segmental hypoplasia or Ask-Upmark kidneys.
A 3-year-old girl was admitted to the emergency department of a general hospital because of a seizure. The day before presentation she had low-grade fever and had vomited several times. There was no history of head injury. On physical examination, she had a generalized convulsion, hypothermia (35.8C), tachycardia (180/min) and slow capillary refill. Her blood pressure could not be measured.
Laboratory investigation revealed CRP <5 mg/l, leucocytes 19.9×109/l, sodium 135 mmol/l, potassium 3.7 mmol/l, calcium 2.2 mmol/l, phosphate 1.7 mmol/l, magnesium 1.22 mmol/l, glucose 10.8 mmol/l, pH 7.44, pCO2 3.7 kPa, bicarbonate 21 mmol/l, base excess –5.1 mmol/l. Blood and urine cultures were collected. Lumbar puncture was not performed because of unstable clinical condition. CT scan of the brain was normal.
Sepsis and /or meningo-encephalitis with septic shock.
The seizures were successfully treated with 2×5 mg rectal diazepam. Because of suspected shock with tachycardia, unmeasurable blood pressure and reduced capillary refill, volume expansion (20 ml/kg NaCl 0.9%) was given three times. Furthermore, the girl was treated with intravenous broad spectrum antibiotics and antiviral medication (acyclovir).
During admission she developed fever (39.6C). After a few hours she had a second convulsion with loss of consciousness and repetitive movements of the right hand, which could not be controlled with intravenous midazolam. At that moment an unexpectedly high blood pressure of 156/119 mm Hg (95th Percentile 110/72 mm Hg) was measured, which made it critical to transfer the patient to the intensive care unit of our tertiary hospital for treatment of malignant hypertension.
On admission, we saw a somnolent girl with cyanotic episodes, temperature 38.3C, blood pressure 140/118 mm Hg and normal capillary refill. Laboratory investigation revealed CRP 37 mg/l, leucocytes 13.4×109/l, urea 5.7 mmol/l, creatinine 34 µmol/l, low potassium (2.2 mmol/l) and metabolic alkalosis (pH 7.49, pCO2 5.3 kPa, bicarbonate 30 mmol/l); analysis of the cerebrospinal fluid was normal. An electro encephalogram (EEG) showed signs of continuous seizure activity. MRI of the brain demonstrated bilateral increased intensity in the area of the cerebral medial and posterior arteries and diffuse abnormalities in the brain stem and basal nuclei (figure 1). This led to the working diagnosis of PRES (see Discussion).
Treatment with valproic acid followed by fenytoin terminated seizure activity. In addition, for treatment of hypertension intravenous labetalol was started. Suppletion of potassium was initiated.
After 24 h intravenous labetalol could be substituted by oral labetalol in combination with amlodipine.
Antibiotics and antiviral medication could be discontinued after 3 days because of sterile cultures and negative PCR of blood and cerebrospinal fluid.
The girl had never complained of headache, vision problems or nose bleedings. She did not eat licorice and never had urinary tract infections or periods of unexplained fever. Echocardiography showed a structurally normal heart with slightly elevated left ventricle wall mass (LVED 36 mm = 95th percentile), indicative of pre-existent hypertension. Funduscopy demonstrated small retinal haemorrhages consistent with malignant hypertension but no signs of chronic hypertensive retinopathy. Renal function and urinary microscopy were normal, but there was significant albuminuria (234 mg/mmol creatinine, normal <20 mg/mmol), indicative of some renal impairment. Furthermore, plasma renin activity (PRA) was extremely high (68 µg/l/h, normal range 0–2.5 μg/l/h).
The combination of elevated PRA with hypokalemia and metabolic alkalosis raised the suspicion of a renal artery stenosis, parenchymal scars after pyelonephritis or a renin-producing tumour, which is extremely rare in children.
Ultrasound of the urinary tract showed a small right kidney (5 cm, - 2SD) and a normal left kidney (7,3 cm, +1 SD). Dimercaptosuccinic acid scintigraphy demonstrated partial loss of function of the right kidney (right-left kidney function 18–82%) without renal scarring. A right renal artery stenosis was suspected but could not be confirmed by angiography. In contrast, angiography demonstrated areas with diffuse hypoplasia of peripheral arteries of both kidneys, which were most pronounced in the upper pole of the right kidney. These findings are very specific for renal segmental hypoplasia, also called Ask-Upmark kidney (figures 2 and and33).
The patient remained normotensive with oral labetalol (max. 8 mg/kg/day) and amlodipine (max. 0.4 mg/kg/day). Suppletion of potassium and fenytoine could be discontinued. Two weeks after admission MRI of the brain was completely normal, supporting the earlier diagnosis of PRES.
Surgical treatment of our patient was considered impossible because the segmental hypoplasia involved both kidneys. Today, one year after diagnosis, the girl is normotensive with monotherapy amlodipine and has normal renal function. Furthermore, microalbuminuria has disappeared and left ventricular dimensions normalized.
Renal segmental hypoplasia or Ask-Upmark kidney has first been described in 8 patients in 19291 Histologically, the affected kidney appears small and contains segments with a decreased number of pyramids, atrophic tubules and no glomeruli. A thin cortex overlies dilated calyces.2 3 Till date, approximately 200 cases have been described. The lesion is generally discovered during childhood or adolescence and is mostly found in females.2 Presenting symptoms are hypertension, haematuria and loin pain.1 2 4 The majority of cases of Ask-Upmark kidneys are unilateral, although bilateral cases have been described.2 5 The aetiology of this renal lesion is unknown. Some authors propose a congenital malformation, whereas others have found significant correlation with vesico-ureteral reflux, indicating an acquired abnormality.2 6
The cause of hypertension in Ask-Upmark kidney(s) is related to an elevated PRA, which, together with high blood pressure, returns to normal after removal of the affected kidney.2 3 In patients with bilateral renal segmental hypoplasia, treatment of hypertension is pharmacological.5 In one small series, end-stage renal disease developed in 4 out of 17 patients with uni- or bilateral Ask-Upmark kidneys.2
Our patient, having bilateral renal lesions consistent with renal segmental hypoplasia, presented with malignant hypertension with hypertensive encephalopathy. She never had symptoms of hypertension before, though echocardiography showed signs of pre-existent high blood pressure. It is possible that dehydration due to vomiting triggered an additional surge in PRA, possibly explaining the development of malignant hypertension. However, too vigorous volume expansion given for suspected shock may have exacerbated our patients condition as well.
The inability to measure the girl's initial blood pressure could be the consequence of not inflating the cuff to a sufficiently high pressure because of a suspected low blood pressure.
The low level of plasma potassium can be explained by elevated PRA causing renal potassium excretion via hyperaldosteronism. In addition, intracellular hydrogen ion shift, in exchange for potassium and enhanced tubular bicarbonate reabsorption due to intracellular acidosis subsequently, may have led to metabolic alkalosis.
Neuroimaging in our patient showed lesions suspect for PRES. This syndrome was first denominated in a case series in 1996.7 It describes the combination of clinical symptoms (headache, confusion, altered level of consciousness, visual disturbances and convulsions) together with specific radiological findings consistent with posterior cerebral white matter oedema. The syndrome has been described at various ages and seems to occur more often in females.8–10 It is related to hypertension, meningo-encephalitis, autoimmune disease, medication (eg, calcineurin inhibitors) and eclampsia.7 In hypertension, cerebral white matter oedema appears to be caused by disordered cerebral autoregulation, leading to increased cerebral blood flow. The subsequent loss of function of the blood–brain barrier causes extravasation of fluid into the brain parenchyma.11 It occurs predominantly in the parieto-occipital part of the cerebral hemispheres, possibly due to locally reduced sympathetic innervation of intracranial arterioles which protect the brain against increases in blood pressure.12 13 PRES can optimally be visualized with MRI. Usually the abnormalities resolve within days to weeks.14 15
Treatment of PRES consists of removing the underlying cause, for example, lowering blood pressure or discontinuing associated drugs and treating convulsions. The prognosis appears to be good,7 16 though one case series reported death in 6 out of 22 patients and persistent neurologic sequelae in a substantial part of survivors,17 evidence that this syndrome is potentially dangerous and the consequence of a serious underlying condition.
Competing interests None.
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