title: The proximal tubule in the pathophysiology of the diabetic kidney.
abstract: Diabetic nephropathy is a leading cause of end-stage renal disease. A better understanding of the molecular mechanism involved in the early changes of the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. This review focuses on the proximal tubule in the early diabetic kidney, particularly on its exposure and response to high glucose levels, albuminuria, and other factors in the diabetic glomerular filtrate, the hyperreabsorption of glucose, the unique molecular signature of the tubular growth phenotype, including aspects of senescence, and the resulting cellular and functional consequences. The latter includes the local release of proinflammatory chemokines and changes in proximal tubular salt and fluid reabsorption, which form the basis for the strong tubular control of glomerular filtration in the early diabetic kidney, including glomerular hyperfiltration and odd responses like the salt paradox. Importantly, these early proximal tubular changes can set the stage for oxidative stress, inflammation, hypoxia, and tubulointerstitial fibrosis, and thereby for the progression of diabetic renal disease.
authors.affiliation: Depts. of Medicine and Pharmacology, University of California San Diego & VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. vvallon@ucsd.edu
authors.forename: Volker
authors.initials: V
authors.lastname: Vallon
mesh_terms: D000042:Absorption; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D016922:Cellular Senescence; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006801:Humans; D006965:Hyperplasia; D006984:Hypertrophy; D018836:Inflammation Mediators / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009395:Nephritis, Interstitial / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D010641:Phenotype; D011507:Proteinuria / Q000378:metabolism / Q000503:physiopathology
chemical_list: D001786:Blood Glucose; D018836:Inflammation Mediators