Institute of Physiology, University of Zurich, Zurich, Switzerland.
Department of Renal Medicine, Royal Free Hospital, University College London, London, UK.
Nat Rev Nephrol. 2023 Jun;19(6):384-400. doi: 10.1038/s41581-023-00699-9. Epub 2023 Apr 4.
The kidneys have a central role in the control of acid-base homeostasis owing to bicarbonate reabsorption and production of ammonia and ammonium in the proximal tubule and active acid secretion along the collecting duct. Impaired acid excretion by the collecting duct system causes distal renal tubular acidosis (dRTA), which is characterized by the failure to acidify urine below pH 5.5. This defect originates from reduced function of acid-secretory type A intercalated cells. Inherited forms of dRTA are caused by variants in SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, WDR72 and probably in other genes that are yet to be discovered. Inheritance of dRTA follows autosomal-dominant and -recessive patterns. Acquired forms of dRTA are caused by various types of autoimmune diseases or adverse effects of some drugs. Incomplete dRTA is frequently found in patients with and without kidney stone disease. These patients fail to appropriately acidify their urine when challenged, suggesting that incomplete dRTA may represent an intermediate state in the spectrum of the ability to excrete acids. Unrecognized or insufficiently treated dRTA can cause rickets and failure to thrive in children, osteomalacia in adults, nephrolithiasis and nephrocalcinosis. Electrolyte disorders are also often present and poorly controlled dRTA can increase the risk of developing chronic kidney disease.
肾脏在酸碱稳态的控制中起着核心作用，这是由于近端小管中重吸收碳酸氢盐以及氨和铵的生成，以及沿着集合管主动分泌酸。集合管系统排酸功能受损会导致远端肾小管性酸中毒（dRTA），其特征是尿液无法酸化至 pH 值低于 5.5。这种缺陷源于酸分泌型 A 闰细胞功能降低。dRTA 的遗传性形式是由 SLC4A1、ATP6V1B1、ATP6V0A4、FOXI1、WDR72 等基因的变异引起的，可能还有其他尚未发现的基因。dRTA 的遗传遵循常染色体显性和隐性模式。获得性 dRTA 是由各种类型的自身免疫性疾病或某些药物的不良反应引起的。不完全性 dRTA 在有和没有肾结石病的患者中经常发现。这些患者在受到挑战时无法适当酸化尿液，表明不完全性 dRTA 可能代表排酸能力谱中的中间状态。未被识别或治疗不足的 dRTA 可导致儿童佝偻病和生长不良、成人骨软化症、肾结石和肾钙质沉着症。电解质紊乱也常存在，且控制不佳的 dRTA 会增加患慢性肾脏病的风险。
