ABSTRACT
The purpose of this study was to elucidate whether the molecular defect of acid-base transporters in renal tubules is related to the functional defect of urinary acidification in distal renal tubular acidosis(RTA). We performed NH4Cl, furosemide, or bicarbonate loading test to evaluate renal acidification function, and immunohistochemistry using antibodies to H+- ATPase, Cl-/HCO3- exchanger(band-3 protein), and Na+/K+-ATPase in kidney tissue in 6 patients with RTA and renal cell carcinoma patients as normal controls. Kidney tissue was obtained either by percutaneous needle biopsy(RTA) or nephrectomy(NC). The results were as follows; 1) In all six RTA patients, proton secretory defect of distal acidification was shown by a failure to lower the urine pH after NH4Cl loading or furosemide test or abnormally low urine-blood pCO2 difference during bicarbonate loading. In two patients with RTA, proximal acidification defect was combined, which was demonstrated by increased fractional excretion of bicarbonate. 2) In normal control, intense H+-ATPase and band-3 protein staining was observed in collecting ducts. 3) In distal RTA patients, H+-ATPase and band- 3 protein staining was not demonstrable or markedly decreased in the intercalated cells of distal nephron. 4) In two patients who had both proximal and distal RTA, H+-ATPase staining was markedly decreased in the brush border of proximal tubules as well as the distal nephron. In conclusion, the defect of acid-base transporters in renal tubule was related with the functional defect of urinary acidification in distal RTA.