Prevalence, diagnosis, and management of secondary pseudohypoaldosteronism

Abstract

Dear Editor: We congratulate Atmis and colleagues for the fascinating case of a 21⁄2-month-old girl with an anomalous urinary tract and a febrile urinary tract infection in spite of antimicrobial prophyl a x i s , wh i c h wa s c omp l i c a t e d b y s e c o n d a r y pseudohypoaldosteronism [1, 2]. Presentation and course of the case were very well documented both clinically and biochemically. We would like to briefly address the prevalence and the diagnostic attitude (with our experience), the differential diagnosis, and the management of secondary pseudohypoaldosteronism in infants with urinary tract infection. Atmis and colleagues [1, 2] apparently suggest that the condition is rare. Furthermore, the determination of renin, aldosterone, adrenocorticotropic hormone, and cortisol seems to be required for diagnosis. It has been speculated that secondary pseudohypoaldosteronism is no rare among infants with a febrile urinary tract infection [3, 4]. In clinical practice, the diagnosis is made in an infant affected by a symptomatic urinary tract infection or an anomalous urinary tract, who is found to have at least two of the following abnormalities: hyponatremia, hyperkalemia, and metabolic acidosis [3–5]. In our experience, secondary pseudohypoaldosteronism is relatively common (Table 1) since, among 96 infants ≥ 4 weeks to ≤ 12 months of age affected by acute pyelonephritis, features consistent with secondary pseudohypoaldosteronism were noted in 29 (30%). Salt-wasting crises due to congenital adrenal hyperplasia may mimic the biochemistry of pseudohypoaldosteronism [6]. However, no more salt-wasting cases due to this condition are noted in most high-income countries, because an efficient neonatal screening has been established [6]. Trimethoprim, often with sulfamethoxazole, is widely prescribed to prevent and treat urinary tract infections. Since trimethoprim functions as a potassium-sparing diuretic [7], it may cause hyponatremia, hyperkalemia, and acidosis. Consequently, urinary tract infections, anomalies of the urinary tract, and drugs [7] nowadays account for almost all cases of this abnormal biochemical pattern in infancy. In secondary pseudohypoaldosteronism, the cornerstone of management of water and salt disturbance consists of fluid resuscitation with an isotonic solution [3]. Normosaline is preferred to repair hyponatremia and lactated Ringer to repair acidosis [3]. Hyperkalemia customarily contraindicates Ringer, because it contains potassium. However, the literature does not support this view [8]. Hyponatremia may be severe (≤ 120 mmol/L) in secondary pseudohypoaldosteronism. Since it develops over ≥ 48 h, a rapid correction risks iatrogenic osmotic demyelination syndrome [9]. Most authorities currently recommend a ≤ 6-mmol/L daily increase in sodium [9]. In pseudohypoaldosteronism, isotonic solutions correct not only volume depletion and hyponatremia but also hyperkalemia [3]. Consequently, treatment of hyperkalemia with ß-agonists, sodium bicarbonate, insulin, fludrocortisone, or cation exchangers is unnecessary. Reduced responsiveness to aldosterone may persist for months after treatment of the underlying infection or repair of the urinary tract anomaly [3]. Hence, long-term supplementation with salt is occasionally required. * Mario G. Bianchetti [email protected]