Distal renal tubular acidosis and high urine carbon dioxide tension in a patient with southeast Asian ovalocytosis

Southeast Asian ovalocytosis (SAO) is the best-documented disease in which mutation in the anion exchanger-1 (AE1) causes decreased anion (chloride [C l-]/bicarbonate [HCO3-]) transport. Because AE1 is also found in the basola teral membrane of type A intercalated cells of the kidney, distal renal tub ular acidosis (dRTA) might develop if the function of AE1 is critical for t he net excretion of acid. Studies were performed in a 33-year-old woman wit h SAO who presented with proximal muscle weakness, hypokalemia (potassium, 2.7 mmol/L), a normal anion gap type of metabolic acidosis (venous plasma p H, 7.32; bicarbonate, 17 mmol/L; anion gap, 11 mEq/L), and a low rate of am monium (NH4+) excretion in the face of metabolic acidosis (26 mu mol/min). However, the capacity to produce NH4+ did not appear to be low because duri ng a furosemide-induced diuresis, NH4+ excretion increased almost threefold to a near-normal value (75 mu mol/L/min). Nevertheless, her minimum urine pH (6.3) did not decrease appreciably with this diuresis. The basis of the renal acidification defect was most likely a low distal H+ secretion rate, the result of an alkalinized type A intercalated cell in the distal nephron . Unexpectedly, when her urine pH increased to 7.7 after sodium bicarbonate administration, her urine minus blood carbon dioxide tension difference (U -B PCO2) was 27 mm Hg. We speculate that the increase in U-B PCO2 might ari se from a misdirection of AE1 to the apical membrane of type A intercalated cells. (C) 1999 by the National Kidney Foundation, Inc.