The proximal tubule in the pathophysiology of the diabetic kidney

Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1009-22. doi: 10.1152/ajpregu.00809.2010. Epub 2011 Jan 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Absorption
  • Animals
  • Blood Glucose / metabolism*
  • Cellular Senescence
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology*
  • Disease Progression
  • Fibrosis
  • Glomerular Filtration Rate*
  • Humans
  • Hyperplasia
  • Hypertrophy
  • Inflammation Mediators / metabolism
  • Kidney Tubules, Proximal / metabolism
  • Kidney Tubules, Proximal / pathology
  • Kidney Tubules, Proximal / physiopathology*
  • Nephritis, Interstitial / metabolism
  • Nephritis, Interstitial / physiopathology
  • Oxidative Stress
  • Phenotype
  • Proteinuria / metabolism
  • Proteinuria / physiopathology


  • Blood Glucose
  • Inflammation Mediators