PRESERVATION OF INTERCALATED CELL H-ATPASE IN 2 PATIENTS WITH LUPUS NEPHRITIS AND HYPERKALEMIC DISTAL RENAL TUBULAR-ACIDOSIS()

In patients with Sjogren's syndrome and a secretory-defect distal rena l tubular acidosis (dRTA), absence of vacuolar H+-ATPase from collecti ng duct intercalated cells has been reported. The H+-ATPase was examin ed in two patients with lupus nephritis and hyperkalemic (presumed vol tage defect) dRTA. Both patients had a positive urine anion gap, alkal ine urine despite acidemia, no rise in urine PCO2 with alkaluria, a ur ine pH > 5.5, and urine potassium excretion rate not significantly inc reased after 80 mg of intravenous furosemide. In both patients, immuno cytochemistry of renal biopsy frozen sections with an anti-H+-ATPase m onoclonal antibody showed bright staining of the proximal tubule brush border and collecting duct intercalated cells. In one patient, routin e immunofluorescence analysis of a frozen section of her kidney biopsy with antihuman IgG showed staining of the collecting duct, indicative of autoantibodies to this segment. Moreover, rat kidney sections incu bated with her serum showed labeling of the intercalated cells. On imm unoblots of human kidney microsomal membranes performed with serum fro m both patients, an immunoreactive polypeptide was observed at M-r app roximately 56 kD that was not seen with control serum. Neither patient 's sera reacted with affinity-purified bovine H+-ATPase or with lysate s from 293 cell fibroblasts in which either of both isoforms of the hu man H+-ATPase B subunit (56 kD) were expressed. These findings demonst rate that the spectrum of dRTA includes the preservation of H+-ATPase in intercalated cells, in patients with presumed voltage defect dRTA. Moreover, some patients may have autoantibodies to the intercalated ce lls that are not directed to subunits of the H+-ATPase.