A patient on long-term topiramate (carbonic anhydrase inhibitor) develops a metabolic acidosis with a urine pH of 6.2 (alkaline relative to the acidemic state). What is the precise tubular defect and what type of renal tubular acidosis does this mimic?
- A Impaired CA II/CA IV in the proximal tubule reducing bicarbonate reabsorption; proximal (type 2) RTA ✓
- B Impaired H⁺-ATPase in the alpha-intercalated cells of the collecting duct; distal (type 1) RTA
- C Reduced aldosterone effect on principal cells impairing Na reabsorption; type 4 RTA
- D Inhibition of NH₃ synthesis in the proximal tubule reducing ammonium buffer; type 4 RTA
Explanation
Carbonic anhydrase II (cytosolic) and CA IV (luminal membrane) in the proximal tubule catalyze the hydration of CO₂ and dehydration of H₂CO₃, which is essential for the reclamation of ~85% of filtered bicarbonate. Topiramate (and acetazolamide) inhibit CA, causing bicarbonate to spill into the urine as the proximal Tm for HCO₃⁻ is effectively lowered — mimicking proximal (type 2) RTA. The urine pH rises above 5.3 during bicarbonate wasting, but once serum HCO₃⁻ falls enough to match the lowered Tm, the kidneys re-acidify urine (pH < 5.5), which distinguishes it from distal RTA.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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