Pathophysiology: Tubulopathies arise from defects in transport proteins or channels in the tubular epithelium, causing abnormal handling of salts, electrolytes, and acid-base balance. Bartter and Gitelman typically cause hypokalemic metabolic alkalosis due to salt wasting; Bartter is often associated with hypercalciuria, while Gitelman presents with hypocalciuria and hypomagnesemia. Proximal tubulopathies such as Fanconi produce glycosuria, aminoaciduria, phosphaturia, bicarbonate loss, and often metabolic acidosis. Distal tubulopathies and RTA forms may produce metabolic acidosis with potassium disturbances and nephrolithiasis risk.
Clinical features: Features vary by condition but commonly include abnormalities in potassium, magnesium, or phosphate levels, metabolic alkalosis or acidosis, polyuria, growth delay in children, muscle cramps, and dehydration. Some forms present in childhood, others in adulthood. Volume status and blood pressure may reflect salt-wasting or retention.
Diagnosis: Diagnosis relies on history and characteristic electrolyte patterns. Laboratory tests assess serum electrolytes, bicarbonate, calcium, phosphate, and magnesium, along with urinary electrolytes and bicarbonate loss. Renin and aldosterone levels can help distinguish Bartter-like from Liddle-like forms, and genetic testing can confirm inherited tubulopathies.
Management: Treatment aims to correct electrolyte disturbances and prevent complications. Bartter: NSAIDs (to reduce prostaglandin-mediated salt loss) and potassium-sparing agents. Gitelman: oral potassium and magnesium supplementation and adequate salt intake. Fanconi: bicarbonate therapy with phosphate and vitamin D as needed. Liddle syndrome: potassium-sparing diuretics. Avoid nephrotoxins and monitor growth and kidney function.