The infant’s ultrasound showed slightly enlarged kidneys (5.1 cm and 5.2 cm in length) and mild bilateral hydronephrosis. Voiding cystourethrogram showed bilateral grade 5 reflux, with no evidence of posterior urethral valves. A urology referral was obtained. The patient was managed in the paediatric critical care unit with conservative therapy, along with frequent monitoring of electrolytes. The empirical steroid therapy started because of presumed congenital adrenal hyperplasia (CAH) was discontinued following the ultrasound results and a negative 17-OH progesterone test. His urine culture was positive for Escherichia coli on initial catheter specimen. Over the course of admission, the patient’s bloodwork abnormalities resolved, including his blood urea nitrogen (from 14.2 mmol/L to 1.4 mmol/L) and creatinine (from 96 μmol/L to 52 μmol/L). His weight improved to the 25th percentile for age, and he was discharged home after completing 14 days of antibiotic therapy on trimethoprim and sulfamethoxazole prophylaxis.
Pseudohypoaldosteronism (PHA) is a recognized, although rare, complication of multiple disease states and medical treatments. Our patient had PHA secondary to a urinary tract infection (UTI). A literature search for PHA caused by vesicoureteric reflux with pyelonephritis revealed a few reported cases in the urological literature, and only one case in the emergency literature (
1–
11). The mechanism is poorly understood, but it is speculated that it is due to aldosterone resistance secondary to endotoxin damage of the aldosterone receptors. This results in a lack of aldosterone response in the distal tubule.
Aldosterone exerts its effect on the distal tubule resulting in an increased uptake of sodium and increased excretion of potassium. Its production is regulated by the renin-angiotensin system. Aldosterone deficit results in hyponatremia and hypovolemia, accompanied by hyperkalemia and metabolic acidosis.
The finding of a combination of hyperkalemia and hyponatremia is relatively rare. It usually signifies hypoaldosteronism or PHA. The main cause of hypoaldosteronism is acute adrenal insufficiency (Waterhouse-Friedrichsen syndrome, Addison’s disease and septic shock) or chronic adrenal insufficiency (Addison’s disease and CAH).
PHA refers to a diffuse group of disorders with renal tubular resistance to aldosterone. PHA is characterized by hyperkalemia, metabolic acidosis and a normal glomerular filtration rate. PHA can be broken down into primary or secondary causes. Primary PHA was first described in 1958, and represents a diverse group of genetic defects causing decreased number or absence of mineralocorticoid receptors. These described syndromes include ‘classic’ PHA-1, multiple target organ defects, early childhood hyperkalemia, renal tubular acidosis type IV subtype 5 and PHA-II (chloride shunt syndrome).
Secondary PHA can be caused by UTIs, obstructive uropathies, renal vein thrombosis and medications (cyclooxygenase inhibitors [nonsteroidal anti-inflammatory drugs], beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, trimethoprim, heparin, calcineurin inhibitors [cyclosporine and tacrolimus] and potassium-sparing diuretics).
Our patient had a clinical presentation that could be consistent with the more common condition of CAH, making the diagnosis of PHA difficult. CAH is an autosomal recessive condition that results in excessive androgen production and a cortisol deficit due to the lack of a specific enzyme activity. Currently, most jurisdictions in the United States and Canada do not have an active screening program. However, many areas are currently in the process of introducing screening programs. These programs screen for the most common enzyme defect, 21-hydroxylase deficiency, and should, therefore, diagnose up to 90% of these infants before complications, and should reduce the number of infants presenting with salt wasting. As these programs become more widespread, the diagnosis of PHA will become an increasingly important diagnosis to consider in infants presenting with hyponatremia and hyperkalemia.
A recent review by Watanabe (
12) of 60 cases of secondary PHA previously reported in the literature revealed some interesting points. All patients were less than seven months of age, 80% suffered from a urinary tract malformation and UTI. Twelve per cent had a urinary tract malformation in the absence of infection, and 8% had a UTI without an underlying malformation. Therefore, one can postulate that either the UTI or the malformation alone can cause secondary PHA, and that age may be a risk factor for its development.
When faced with electrolyte abnormalities such as hyperkalemia and hyponatremia, one must consider not only hypoaldosteronism (as in CAH), but also aldosterone resistance. Because this was a four-week-old infant, the initial management did not differ significantly. Management priorities in this case were centred around treatment of sepsis despite well appearance, correction of dehydration, and correction and monitoring of electrolyte abnormalities. In this case of secondary PHA due to a UTI and bilateral grade 5 reflux, the initiation of antibiotics was very important.
