tubulopathy

Tubulopathy is a disorder arising from dysfunction of the renal tubules, the parts of the nephron responsible for reabsorbing water, electrolytes, and nutrients, and for secreting waste. Tubulopathies can cause electrolyte disturbances, acid–base abnormalities, and abnormal urinary losses. They may be inherited as primary disorders of specific tubular segments or acquired secondary to medications, ischemia, toxins, or systemic disease.

The spectrum includes proximal tubulopathies such as Fanconi syndrome, which features generalized proximal tubular dysfunction with glycosuria despite normal blood glucose, aminoaciduria, phosphaturia, bicarbonate wasting, and metabolic acidosis; distal tubulopathies such as Bartter and Gitelman syndromes; and renal tubular acidosis (types 1, 2, and 4) reflecting defects in distal acid secretion or proximal bicarbonate reabsorption. Other acquired tubulopathies arise with nephrotoxin exposure (for example certain chemotherapeutic agents and amphotericin B) or ischemic injury.

Clinical features vary by disorder but common signs include polyuria, polydipsia, dehydration, growth failure in children, muscle cramps, and fatigue due to electrolyte disturbances such as hypokalemia, hypophosphatemia, hypomagnesemia, or metabolic acidosis or alkalosis. Diagnosis combines serum electrolytes and bicarbonate, urinary electrolytes, urine glucose, aminoaciduria, and sometimes genetic testing or urinary acidification tests.

Management focuses on treating the underlying cause and correcting electrolyte abnormalities through careful supplementation (potassium, magnesium, phosphate), bicarbonate for acidosis, and hydration; avoiding nephrotoxins; and in select tubulopathies addressing specific mechanisms (for example NSAIDs in Bartter syndrome). Prognosis depends on the underlying condition and response to treatment, with many patients requiring lifelong monitoring for electrolyte balance and bone health.