[Investigations on the pathogenesis of distal renal tubular acidosis (author's transl)]

In distal (type 1) RTA, renal acid excretion is impaired by the inability to establish adequate pH gradients between plasma and distal tubular fluid at any level of acidosis. Main clinical signs in infancy are anorexia, vomiting and failure to thrive. Despite low serum bicarbonate levels the renal threshold of bicarbonate is normal, while urinary pH levels are high even with values below the threshold. Under conditions of bicarbonate-induced systemic alkalosis urinary the pCO2 exceeds blood pCO2 in normal subjects. by contrast, the urinary pCO2 tension is not significantly greater in distal RTA, indicating a failure of the cells of the distal nephron to secrete hydrogen ions even without a gradient. Red cell carbonic anhydrase is within the normal range, whilst the inhibition of carbonic anhydrase activity has no effect on distal tubular function. Until now no histological or enzymatic defect could be detected to explain the ineffective acidification. Bicarbonate loading is followed by a lowering of calcium excretion to within the normal range and a decrease in the uncharacteristic renal hyperaminoaciduria.