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A rare renal tubulopathy secondary to urinary tract infection (UTI) and/or urinary tract malformation (UTM) characterized by renal tubular resistance to aldosterone, characterized by hyponatremia, metabolic acidosis, hyperkalemia and inappropriately high serum aldosterone concentration and clinically manifesting as dehydration, vomiting, and poor oral intake.
ORPHA:93164Classification level: Disorder
- Secondary pseudohypoaldosteronism
- Prevalence: -
- Inheritance: Not applicable
- Age of onset: Infancy
- ICD-10: N15.8
- OMIM: -
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
So far, less than 100 cases have been reported worldwide. Because of its association with underlying UTMs, there is a strong male preponderance with more than 80% of affected infants being males. Due to the non-specific manifestations, the true prevalence of transient pseudohypoaldosteronism (TPHA1) is possibly underestimated.
TPHA1 occurs exclusively during the neonatal or early infantile period (90 % during the first six months of life). The clinical course is transient, typically resolving with treatment of the UTI, and may range from asymptomatic to life-threatening. The clinical features are non-specific and include nausea, vomiting, poor activity and low oral intake. As a consequence, life-threating salt loss, hyperkalemia and hemodynamic compromise may occur.
Risk factors for TPHA1 in infants with UTI include male sex, young age and urinary tract malformation. Young age may contribute to the development of TPHA1 through low renal mineralocorticoid receptor expression and physiological partial aldosterone resistance. Urinary tract malformation has been found to be associated with decreased expression of mineralocorticoid receptor and increase in mineralocorticoid receptor resistance. In addition, bacterial factors including bacterial endotoxins and host factors such as TGF-beta, INF-alpha, IL-1 and -6 have also been speculated to involve the pathogenesis of TPHA1 in infants with UTI.
The diagnosis can be confirmed by the findings of inappropriately elevated serum aldosterone in the setting of hyponatremia with renal sodium wasting, hyperkalemia with impaired renal potassium excretion, and non-anion gap metabolic acidosis. Infants should be screened for UTI and UTMs.
The differential diagnoses include patients with impaired renal function (chronic kidney disease stage III to V), pre-existing electrolyte imbalance, medications (Na channel blockers, mineralocorticoid receptor blockers, calcineurin inhibitors, angiotensin converting enzyme inhibitors) which may cause pseudohypoaldosteronism. In cases of recurrent or persistent pseudohypoaldosteronism, the differential diagnosis should include pseudohypoaldosteronism type 1.
TPHA1 is not an inherited condition; however, in the cases of recurrent or persistent pseudohypoaldosteronism after treatment, the genetic analysis for the genes responsible for PHA1 may be considered.
Management and treatment
Early recognition and prompt treatment is crucial for affected infants with life-threatening hyperkalemia, salt wasting, and acidosis. The mainstays of treatment include antibiotics for UTI, volume repletion with salt supplementation for hyponatremia and in some cases bicarbonate for correction of metabolic acidosis. The need for additional therapeutic measures, such as loop diuretics, beta2 agonist, ion exchange resins, and calcium gluconate are determined by the severity of hyperkalemia.
The outcome is typically favorable as TPHA1 resolves with treatment of dehydration and urinary tract infection; however, the prognosis for affected infants with life-threatening hyperkalemia, salt wasting, and acidosis depends on early recognition and prompt treatment.