ABSENCE OF H-ATPASE IN THE INTERCALATED CELLS OF RENAL TISSUES IN CLASSIC DISTAL RENAL TUBULAR-ACIDOSIS()

Proton-secretory defect is thought to be a major pathophysiologic mech anism leading to classic distal renal tubular acidosis (dRTA). However , then have been only two case reports demonstrating the absence of pr oton pump in renal tissues of the patients with Sjogren's syndrome. Th is study presents two cases of classic dRTA in which the absence of in tact H+-ATPase was shown in their renal biopsy tissues by immunohistoc hemistry using a rabbit polyclonal antibody against the 70 kDa catalyt ic subunit of H+-ATPase from bovine brain clathrin-coated vesicles; on e of the cases is diagnosed as subclinical Sjogren's syndrome and the other is idiopathic dRTA, a normal human kidney (NC) and the renal bio psy tissues from a patient with chronic tubulointerstitial nephritis w hose proton secretory capacity was intact (DC) were compared as contro ls. The first patient, a 26-year-old woman, presented with quadripares is. Her serologic tests revealed positive autoantibodies (ANA, SSA; SS B & RF), and a lower lip biopsy confirmed the diagnosis of Sjogren's s yndrome. The second patient, a 43-year-old woman, who initially presen ted with a pathologic fracture of both femoral necks was referred for an evaluation for hypokalemia by the Department of Orthopedic Surgery. Her renal ultrasonography showed medullary calcification, and no auto antibodies were positive. Serum electrolytes and blood gas analyses of the two patients indicated severe hypokalemia and metabolic acidosis, and proton secretory defects were shown by a failure to lower the uri ne pH during marked acidemia induced by NH4Cl loading and on abnormall y low urine-blood pCO(2) difference during bicarbonate administration. While stainings with the anti-H+-ATPase antibody in NC and DC were st rongly positive in intercalated cells in the connecting tubules and co llecting ducts, the tissues from both patients with dRTA were devoid o f any anti-H+-ATPase staining in the intercalated cells. These results support that the pathophysiologic basis of impaired H+ secretion in i diopathic classic dRTA as well as Sjogren's syndrome is the absence of intact H+-ATPase pumps in the intercalated cells.