title: Tubular atrophy in the pathogenesis of chronic kidney disease progression.
abstract: The longstanding focus in chronic kidney disease (CKD) research has been on the glomerulus, which is sensible because this is where glomerular filtration occurs, and a large proportion of progressive CKD is associated with significant glomerular pathology. However, it has been known for decades that tubular atrophy is also a hallmark of CKD and that it is superior to glomerular pathology as a predictor of glomerular filtration rate decline in CKD. Nevertheless, there are vastly fewer studies that investigate the causes of tubular atrophy, and fewer still that identify potential therapeutic targets. The purpose of this review is to discuss plausible mechanisms of tubular atrophy, including tubular epithelial cell apoptosis, cell senescence, peritubular capillary rarefaction and downstream tubule ischemia, oxidative stress, atubular glomeruli, epithelial-to-mesenchymal transition, interstitial inflammation, lipotoxicity and Na(+)/H(+) exchanger-1 inactivation. Once a a better understanding of tubular atrophy (and interstitial fibrosis) pathophysiology has been obtained, it might then be possible to consider tandem glomerular and tubular therapeutic strategies, in a manner similar to cancer chemotherapy regimens, which employ multiple drugs to simultaneously target different mechanistic pathways.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, USA. jeffrey.schelling@case.edu.|Rammelkamp Center for Education and Research, MetroHealth Medical Center, 2500 MetroHealth Drive, Rammelkamp Building, R425, Cleveland, OH, 44109, USA. jeffrey.schelling@case.edu.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Schelling
mesh_terms: D000818:Animals; D001284:Atrophy; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D006801:Humans; D007684:Kidney Tubules / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D012079:Renal Circulation; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015398:Signal Transduction
keywords: Apoptosis; Chronic kidney disease; Interstitial fibrosis; Lipotoxicity; NHE1