On the mechanism of impaired distal acidification in hyperkalemic renal tubular acidosis: Evaluation with amiloride and bumetanide

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 valtage (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 woth a comparable degree of rental 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). Patients in Group I and Group II had a similar degree of metabolic acidosis and 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 but resulted in an increase in potssium excretion similar to that seen in controls and Group I patients. These findings suggest that a derangement other than a voltage-dependent defects is responsible for the inability, characteristic of Groups II patients, to lower their pH. It was concluded that impairment in urinary acidification observed in patients with this subtype of hyperkalemic DRTA is due to a defects in collecting tubule hydrogen secretion that results from H+ ATPase dysfunction rather than from a voltage-dependent defect.