Incomplete distal renal tubular acidosis coinherited with a mutation in the band 3 (AE1) gene.

Abstract

Band 3 (anion exchanger 1, AE1) is one of the most abundant proteins of the erythrocyte membrane. We have previously characterized twenty AE1 gene defects underlying spherocytic haemolytic anaemia with band 3 deficiency. Since AE1 is also expressed in the intercalated cells of renal cortical collecting ducts where it is thought to participate in urine acidification, we asked whether the spherocytogenic AE1 mutations also affect the regulation of urine acidity. We examined 10 patients from seven unrelated families with hereditary spherocytosis with band 3 deficiency using the short urine acidification test with CaCl2 administration at a dose of 0.2 g/kg b.w. To asses the ability of the nephron to secrete protons, 400 ml of NaHCO3 were infused over a period of 2 h. While we detected no significant abnormalities in eight patients, we have diagnosed incomplete distal renal tubular acidosis (dRTA) in two patients from one family whose urinary pH 5 h after CaCl2 administration were 6.56 and 6.89. Administration of bicarbonate in these two patients resulted in high urinary HCO3- concentration. The patients carry the previously characterized mutation band 3PRIBRAM that encodes a C-terminally truncated band 3 containing only the cytoplasmic domain and the first three putative transmembrane segments. This finding shows an association of a band 3 defect with abnormal urinary acidification perhaps secondary to Cl-/HCO3- exchange in the basolateral membrane of alpha-intercalated cells of cortical collecting ducts.