Red blood cell AE1/Band 3 transports in dominant distal renal tubular acidosis patients

Abstract Introduction Anion exchanger 1 (AE1) (SLC4A1 gene product) is a membrane protein expressed in both kidney and Red Blood Cells (RBC): it exchanges extracellular bicarbonate (HCO3-) for intracellular chloride (Cl-) and participates to acid-base homeostasis. AE1 mutations in kidney α-intercalated cells can lead to distal renal tubular acidosis (dRTA). In RBC, AE1 (known as Band 3) is also implicated in membrane stability: deletions can cause South Asian Ovalocytosis (SAO). Methods We retrospectively collected clinical and biological data from patients harboring dRTA due to a SLC4A1 mutation and analyzed HCO3- and Cl- transports (by stopped-flow spectrophotometry) and expression (by both flow cytometry, FACS, and Coomassie blue staining) in RBC, as well as RBC membrane stability (ektacytometry). Results Fifteen patients were included: All experienced nephrolithiasis and/or nephrocalcinosis, 2 had SAO and dRTA (dRTA SAO+), 13 dominant dRTA (dRTA SAO-). The latter did not exert specific RBC membrane anomalies. Both HCO3- and Cl- transports were lower in dRTA SAO+ than in dRTA SAO- or controls. Using 3 different extracellular probes, we report a decreased expression (by 52%, p Conclusion Band 3 transport function and expression in RBC from dRTA SAO- patients is normal. However, in SAO RBCs, impaired conformation of AE1/Band 3 corresponds to an impaired function. Thus, the driver of acid-base defect during dominant dRTA is probably an impaired membrane expression.