Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes

J Clin Invest. 2001 Jan;107(2):217-24. doi: 10.1172/JCI10963.


In early diabetes, the kidney grows and the glomerular filtration rate (GFR) increases. This growth is linked to ornithine decarboxylase (ODC). The study of hyperfiltration has focused on microvascular abnormalities, but hyperfiltration may actually result from a prior increase in capacity for proximal reabsorption which reduces the signal for tubuloglomerular feedback (TGF). Experiments were performed in Wistar rats after 1 week of streptozotocin diabetes. Kidney weight, ODC activity, and GFR were correlated in diabetic and control rats given difluoromethylornithine (DFMO; Marion Merrell Dow, Cincinnati, Ohio, USA) to inhibit ODC. We assessed proximal reabsorption by micropuncture, using TGF as a tool for manipulating single-nephron GFR (SNGFR), then plotting proximal reabsorption versus SNGFR. ODC activity was elevated 15-fold in diabetic kidneys and normalized by DFMO, which also attenuated hyperfiltration and hypertrophy. Micropuncture data revealed an overall increase in proximal reabsorption in diabetic rats too great to be accounted for by glomerulotubular balance. DFMO prevented the overall increase in proximal reabsorption. These data confirm that ODC is required for the full effect of diabetes on kidney size and proximal reabsorption in early streptozotocin diabetes and are consistent with the hypothesis that diabetic hyperfiltration results from normal physiologic actions of TGF operating in a larger kidney, independent of any primary malfunction of the glomerular microvasculature.

Publication types

  • Comment
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carboxy-Lyases / metabolism
  • Diabetes Mellitus, Experimental / enzymology
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetic Nephropathies / enzymology
  • Diabetic Nephropathies / physiopathology*
  • Eflornithine / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Glomerular Filtration Rate
  • Hypertrophy
  • Kidney / pathology
  • Kidney / physiopathology*
  • Kidney Tubules, Proximal / physiopathology
  • Male
  • Organ Size
  • Ornithine Decarboxylase / blood
  • Ornithine Decarboxylase / metabolism*
  • Ornithine Decarboxylase Inhibitors
  • Perfusion
  • Proteins / metabolism
  • Rats
  • Rats, Wistar


  • Enzyme Inhibitors
  • Ornithine Decarboxylase Inhibitors
  • Proteins
  • ornithine decarboxylase antizyme
  • Carboxy-Lyases
  • Ornithine Decarboxylase
  • arginine decarboxylase
  • Eflornithine