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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\u2013specific 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\u20101, diabetes insipidus, etc.) affecting salt, potassium, and water balance. In parallel, studies on specific transporters (H<jats:sup>+<\/jats:sup>\u2010ATPase, anion exchanger 1) in intercalated cells have revealed the mechanisms of related tubulopathies like distal renal distal tubular acidosis or Sj\u00f6gren 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).<\/jats:p>","DOI":"10.1111\/joim.13552","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T05:10:17Z","timestamp":1659330617000},"page":"4-22","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mechanistic insights into the primary and secondary alterations of renal ion and water transport in the distal nephron"],"prefix":"10.1111","volume":"293","author":[{"given":"Nahid","family":"Tabibzadeh","sequence":"first","affiliation":[{"name":"Laboratoire de Physiologie R\u00e9nale et Tubulopathies Centre de Recherche des 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