Laboratoire de Physiologie Rénale et Tubulopathies, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris Cité, Paris, France.
EMR 8228 Unité Métabolisme et Physiologie Rénale, CNRS, Paris, France.
J Intern Med. 2023 Jan;293(1):4-22. doi: 10.1111/joim.13552. Epub 2022 Aug 21.
The kidneys, by equilibrating the outputs to the inputs, are essential for maintaining the constant volume, pH, and electrolyte composition of the internal milieu. Inability to do so, either because of internal kidney dysfunction (primary alteration) or because of some external factors (secondary alteration), leads to pathologies of varying severity, leading to modification of these parameters and affecting the functions of other organs. Alterations of the functions of the collecting duct (CD), the most distal part of the nephron, have been extensively studied and have led to a better diagnosis, better management of the related diseases, and the development of therapeutic tools. Thus, dysfunctions of principal cell-specific transporters such as ENaC or AQP2 or its receptors (mineralocorticoid or vasopressin receptors) caused by mutations or by compounds present in the environment (lithium, antibiotics, etc.) have been demonstrated in a variety of syndromes (Liddle, pseudohypoaldosteronism type-1, diabetes insipidus, etc.) affecting salt, potassium, and water balance. In parallel, studies on specific transporters (H -ATPase, anion exchanger 1) in intercalated cells have revealed the mechanisms of related tubulopathies like distal renal distal tubular acidosis or Sjögren syndrome. In this review, we will recapitulate the mechanisms of most of the primary and secondary alteration of the ion transport system of the CD to provide a better understanding of these diseases and highlight how a targeted perturbation may affect many different pathways due to the strong crosstalk and entanglements between the different actors (transporters, cell types).
肾脏通过平衡输出与输入，对于维持内环境的恒定容量、pH 值和电解质组成至关重要。如果不能做到这一点，无论是由于肾脏内部功能障碍（原发性改变）还是由于某些外部因素（继发性改变），都会导致严重程度不同的病理改变，从而改变这些参数并影响其他器官的功能。收集管 (CD) 的功能改变，CD 是肾单位的最远端部分，已经得到了广泛的研究，并导致了更好的诊断、更好的相关疾病管理以及治疗工具的发展。因此，由于突变或环境中存在的化合物（锂、抗生素等）导致的主细胞特异性转运体（如 ENaC 或 AQP2）或其受体（盐皮质激素或血管加压素受体）的功能障碍，已经在多种综合征中得到证实（Liddle、假性醛固酮增多症 1 型、尿崩症等），这些综合征会影响盐、钾和水的平衡。同时，对闰细胞中特定转运体（H+-ATPase、阴离子交换器 1）的研究揭示了相关的 tubulopathies 机制，如远端肾小管酸中毒或干燥综合征。在这篇综述中，我们将总结 CD 离子转运系统的大多数原发性和继发性改变的机制，以更好地理解这些疾病，并强调由于不同参与者（转运体、细胞类型）之间的强烈串扰和纠缠，靶向干扰可能会如何影响许多不同的途径。
