Observations on the pathogenesis of renal tubular acidosis

Abstract

The responses of five adult patients with renal tubular acidosis to maneuvers designed to elucidate tubular function are compared to the responses of control subjects. After oral administration of ammonium chloride, a greater degree of acidosis developed in the patients with renal tubular acidosis than in the control subjects, they excreted less NH 4 + and HCO 3 − in the urine, and had a smaller drop in urine pH. The failure of HCO 3 − excretion to increase in three of these patients when their serum HCO 3 − levels were raised to normal indicates that diminished tubular HCO 3 − reabsorptive capacity is not the fundamental lesion in the disease. Urinary NH 4 + levels in renal tubular acidosis, although low in relation to the degree of systemic acidosis, proved to be higher than in the urines of equivalent pH of control subjects, suggesting that the capacity for tubular NH 4 + formation is not impaired in renal tubular acidosis. Inability to lower the pH of the urine appropriately is considered to be the primary disorder in renal tubular acidosis, continued HCO 3 − excretion and subnormal ammonia transfer into the urine being secondary phenomena. In spite of the relatively low urinary concentration of free hydrogen ion in renal tubular acidosis the total combined urinary hydrogen (titratable acidity) could be markedly increased by oral or intravenous phosphate loads. Orally administered neutral sodium phosphate (pH 7.4) corrected metabolic acidosis in one patient with renal tubular acidosis by increasing urinary titratable acidity without lowering pH. An adequate explanation for the inability of the patient with renal tubular acidosis to acidify the urine was not provided. Carbonic anhydrase deficiency seems an unlikely possibility because of the demonstrated ability of the patient with renal tubular acidosis to increase HCO 3 − reabsorbtion and titratable acidity.