Bertocchio, J-P;
Genetet, S;
Da Costa, L;
Walsh, SB;
Knebelmann, B;
Galimand, J;
Bessenay, L;
... Mouro-Chanteloup, I; + view all
(2020)
Red Blood Cell AE1/Band 3 Transports in Dominant Distal Renal Tubular Acidosis Patients.
Kidney International Reports
, 5
(3)
pp. 348-357.
10.1016/j.ekir.2019.12.020.
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Abstract
Introduction: Anion exchanger 1 (AE1) (SLC4A1 gene product) is a membrane protein expressed in both kidney and red blood cells (RBCs): it exchanges extracellular bicarbonate (HCO3–) for intracellular chloride (Cl–) and participates in 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 flow cytometry, fluorescence activated cell sorting, and Coomassie blue staining) in RBCs, as well as RBC membrane stability (ektacytometry). Results: Fifteen patients were included. All experience 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 patients with dRTA SAO+ than in those with dRTA SAO− or controls. Using 3 different extracellular probes, we report a decreased expression (by 52%, P < 0.05) in dRTA SAO+ patients by fluorescence activated cell sorting, whereas total amount of protein was not affected. Conclusion: Band 3 transport function and expression in RBCs 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.
| Type: | Article |
|---|---|
| Title: | Red Blood Cell AE1/Band 3 Transports in Dominant Distal Renal Tubular Acidosis Patients |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ekir.2019.12.020 |
| Publisher version: | http://dx.doi.org/10.1016/j.ekir.2019.12.020 |
| Language: | English |
| Additional information: | © 2020 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | acidosis, renal tubular, anion exchange protein 1, erythrocyte, hematologic diseases, nephrocalcinosis, nephrolithiasis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10096934 |
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