On the mechanism of impaired distal acidification in hyperkalemic renal tubular acidosis

It has been postulated that a distinctive type of hyperkalemic distal renal tubular acidosis (DRTA), referred to as voltage-dependent DRTA, results from diminished potassium and hydrogen ion secretion in the distal nephron, which is due to a suboptimal voltage (lumen negative) as a result of impaired sodium reabsorption. To test for the presence of a voltage-dependent DRTA, we used amiloride (20 mg oral, single dose) and bumetanide (2 mg oral, single dose) to inhibit and to stimulate voltage-dependent potassium and hydrogen ion secretion, respectively. Eighteen patients with hyperkalemic DRTA and seven controls with a comparable degree of renal impairment were studied. Patients were subdivided in two groups on the basis of their ability to lower their urine pH during spontaneous acidosis. Patients in Group I lowered their urine pH to the level of controls (5.29 +/- 0.06 and 5.37 +/- 0.11, respectively) whereas patients in Group II could not lower their urine pH below 5.5 (6.38 +/- 0.11). Patients in Group I and Group II had a similar degree of metabolic acidosis and hyperkalemia whereas controls had neither acidosis or hyperkalemia. Most patients in Group II and all patients in Group I had low plasma aldosterone levels. The administration of amiloride resulted in an increase in urine pH and a decrease in potassium excretion in all three groups. The finding that amiloride, presumably by obliterating the transtubular voltage as a result of blockade of sodium transport, inhibited potassium excretion to about the same extent in both groups of patients and in controls argues against the existence of a voltage-dependent defect. Bumetanide produced a fall in urine pH below 5.5 and an increase in potassium excretion in controls and Group I patients. In Group II patients, bumetanide failed to elicit a fall in urine pH below 5.5 but resulted in an increase in potassium excretion similar to that seen in controls and Group I patients. These findings suggest that a derangement other than a voltage-dependent defect is responsible for the inability, characteristic of Group II patients, to lower their urine pH. It was concluded that the impairment in urinary acidification observed in patients with this subtype of hyperkalemic DRTA is due to a defect in collecting tubule hydrogen secretion that results from H+ ATPase dysfunction rather than from a voltage-dependent defect.