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Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney

Volker Vallon1, Scott C Thomson

  • 1Department of Medicine, University of California San Diego, La Jolla, California 92093, USA. vvallon@ucsd.edu

Annual Review of Physiology
|February 17, 2012
PubMed

Insights

Early diabetes causes kidney enlargement and increased filtration rate (GFR) in some patients. This review proposes a tubular hypothesis linking early tubular changes to these risk factors for diabetic nephropathy.

Area of Science:

  • Nephrology
  • Diabetology
  • Renal Physiology

Background:

  • Diabetes mellitus progressively damages the kidneys.
  • Early-stage diabetes can cause kidney hypertrophy and supranormal glomerular filtration rate (GFR).
  • These early changes are significant risk factors for developing diabetic nephropathy.

Purpose of the Study:

  • To present a pathophysiological concept focusing on the renal tubular system to explain early diabetic kidney changes.
  • To elucidate the mechanisms behind kidney enlargement and increased GFR in early diabetes.
  • To explore the role of tubular changes in the progression to diabetic nephropathy.

Main Methods:

  • Review of existing literature on diabetic nephropathy pathophysiology.
  • Focus on the tubular hypothesis of glomerular filtration.
  • Analysis of molecular pathways involved in tubular cell response to diabetes.

Main Results:

  • Early tubular growth and enhanced sodium-glucose cotransport increase proximal tubule reabsorption.
  • Tubuloglomerular feedback mechanisms contribute to supranormal GFR.
  • Diabetic conditions induce tubular cell proliferation, followed by cell cycle arrest and hypertrophy, leading to a senescence-like phenotype.

Conclusions:

  • The tubular hypothesis provides a framework for understanding early diabetic kidney alterations.
  • Molecular pathways like TGF-β and CDK inhibitors mediate tubular hypertrophy and senescence.
  • These activated pathways may predispose the kidney to tubulointerstitial injury and diabetic nephropathy.

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