What causes hypokalemic (classic) distal renal tubular acidosis (type I)?

Updated: Sep 03, 2020
  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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In hypokalemic dRTA, also known as classic RTA or type I RTA, the deficiency is secondary to 2 main pathophysiological mechanisms: (1) a secretory defect and (2) a permeability defect.

When a secretory defect predominates, the decreased secretion of protons (H+) fails to maximally decrease the urinary pH. A decrease in the formation of titratable acidity (TA) and in ammonium trapping and secretion results in systemic acidosis. The mechanism of the hypokalemia is unclear, but hypotheses include (1) increased leakage of K+ into the lumen, (2) volume contraction due to urinary sodium loss and resulting in aldosterone stimulation that increases potassium losses, and (3) decreased proximal K+ reabsorption due to acidemia and hypocapnia.

When a permeability defect predominates, the CD proton pump functions normally, but the high intratubular concentration of H+ dissipates due to abnormal permeability of the tubular epithelium.

Incomplete distal renal tubular acidosis is another clinically important entity. It is considered a variant/milder form (forme fruste) of type I RTA, in which the plasma bicarbonate concentration is normal, but there is a defect in tubular acid secretion. However, daily net acid excretion is maintained by increased ammoniagenesis. Hypercalciuria and hypocitraturia are present, so there is a propensity to nephrolithiasis and nephrocalcinosis. Most of the cases are those of idiopathic calcium phosphate stone formers, relatives of individuals with RTA or with unexplained osteoporosis. Any idiopathic stone former should be evaluated to exclude incomplete type I RTA (by NH4Cl infusion).

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