title: The Tubulointerstitial Pathophysiology of Progressive Kidney Disease.
abstract: Accumulating evidence suggests that the central locus for the progression of CKD is the renal proximal tubule. As injured tubular epithelial cells dedifferentiate in attempted repair, they stimulate inflammation and recruit myofibroblasts. At the same time, tissue loss stimulates remnant nephron hypertrophy. Increased tubular transport workload eventually exceeds the energy-generating capacity of the hypertrophied nephrons, leading to anerobic metabolism, acidosis, hypoxia, endoplasmic reticulum stress, and the induction of additional inflammatory and fibrogenic responses. The result is a vicious cycle of injury, misdirected repair, maladaptive responses, and more nephron loss. Therapy that might be advantageous at one phase of this progression pathway could be deleterious during other phases. Thus, interrupting this downward spiral requires narrowly targeted approaches that promote healing and adequate function without generating further entry into the progression cycle.
authors.affiliation: Division of Kidney Diseases, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL. Electronic address: Schnaper@northwestern.edu.
authors.forename: H William
authors.initials: HW
authors.lastname: Schnaper
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000378:metabolism / Q000473:pathology; D000818:Animals; D054337:Cell Dedifferentiation; D018450:Disease Progression; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D006706:Homeostasis; D006801:Humans; D006965:Hyperplasia / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology*; D009395:Nephritis, Interstitial / Q000150:complications* / Q000503:physiopathology*; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000503:physiopathology*
keywords: CKD; Fibrosis; Proximal tubule; Remnant nephron