The aim of this study was to investigate cortical collecting tubule (CCT) function in normal individuals and in patients with distal renal tubular acidosis (DRTA) using furosemide (80 mg orally) as a tool to stimulate H+ and K+ section by enhancing Na delivery and transport in this nephron segment. In ten normal subjects, furosemide resulted in a fall in urine pH below 5.5 and an increase in net acid and K+ excretion. These effects were obliterated by amiloride, a drug which decreases transtubular epithelial voltage (lumen-negative) in the CCT by blocking Na reabsorption. In 13 patients with DRTA, defined by failure to lower urine pH below 5.5 during acidemia, three distinctive responses to furosemide were found. In six patients with the hyperkalemic variety, furosemide failed to lower urine pH below 5.5 and resulted in a blunted increase in K+ excretion, thereby suggesting that a normal transtubular voltage in the CCT could not be generated in such patients. In five patients with classic RTA, furosemide failed to lower urine pH below 5.5, but K+ excretion increased normally. The increase in K+ excretion indicated that a normal transtubular voltage in the CCT could be generated, while the inability to lower urine pH denotes the presence of a proton pump defect involving the CCT. In two patients with classic RTA, furosemide resulted in both a normal fall in urine pH and an increase in K+ excretion, thereby indicating that the CCT was normal in regards to both proton pump function and in its ability to generate a normal transtubular voltage. By exclusion, their defect in distal acidification was ascribed to a proton pump defect confined to the medullary portion of the collecting tubule. These patterns were also found after the administration of sodium sulfate. It is proposed that evaluation of the ability to lower urine pH and increase K+ excretion after furosemide or sodium sulfate may allow for the characterization of the type of defect underlying the DRTA syndromes and its localization within the collecting tubule.
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