What causes proximal renal tubular acidosis (type II [bicarbonate-wasting acidosis)?

Updated: Sep 03, 2020
  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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The proximal convoluted tubule (PCT) is the major site for reabsorption of filtered bicarbonate. In proximal RTA (pRTA), bicarbonate reabsorption is defective. Proximal RTA rarely occurs as an isolated defect of bicarbonate transport and is usually associated with multiple PCT transport defects; therefore, urinary loss of glucose, amino acids, phosphate, uric acid, and other organic anions, such as citrate, can also occur (Fanconi syndrome).

A distinctive feature of type II pRTA is that it is nonprogressing, and when the serum bicarbonate is reduced to approximately 15 mEq/L, a new transport maximum for bicarbonate is established and the proximal tubule is able to reabsorb all of the filtered bicarbonate. A fractional excretion of bicarbonate (FE[HCO3-]) greater than 15% when the plasma bicarbonate is normal after bicarbonate loading is diagnostic of pRTA. In contrast, the fractional excretion of bicarbonate in low and normal bicarbonate levels is always less than 5% in distal RTA (dRTA). Another feature of pRTA is that the urine pH can be lowered to less than 5.5 with acid loading.

The pathogenic mechanisms responsible for the tubular defect in persons with pRTA are not completely understood. Defective pump secretion or function, namely aberrations in the function of the proton pump ([H+ adenosine triphosphatase [ATPase]), [7] the Na+/H+ antiporter, and the basolateral membrane Na+/K+ ATPase, impair bicarbonate reabsorption. Deficiency of carbonic anhydrase (CA) in the brush-border membrane or its inhibition also results in bicarbonate wasting. Finally, structural damage to the luminal membrane with increased bicarbonate influx or a failure of generated bicarbonate to exit is a proposed mechanism that does not currently have strong experimental backing.

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