This Month's Highlights

[摘要] Inherited forms of distal renal tubular acidosis (dRTA) have been linked to mutations in the human gene encoding the AE1 Cl−/HCO3− exchanger (SLC4A1). A mouse knockout model lacking AE1 (slc4a1−/−) described by Stehberger et al. has autosomal recessive classical dRTA with hyperchloremic metabolic acidosis, low net acid excretion, and inappropriately alkaline urine without bicarbonaturia. Basolateral Cl−/HCO3− exchange activity in acid-secretory intercalated cells of isolated perfused slc4a1−/− cortical collecting duct was reduced, but alternate bicarbonate transport pathway(s) were upregulated. The heterozygote mice (slc4a1−/+) had no apparent defect in acidification, whereas the homozygous mice had dRTA and nephrocalcinosis associated with hypercalciuria, hyperphosphaturia, and hypocitraturia. The slc4a1−/− mouse is the first genetic model of complete dRTA and demonstrates that the AE1 Cl−/HCO3− exchanger is required for maintenance of normal acid–base homeostasis with distal renal regeneration of bicarbonate as a critical part of net acid excretion in the mouse as well as humans. See Stehberger et al., pages 1408–1418.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome