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Glomerular response to hyperglycemia in human diabetic nephropathy
A Remuzzi1, G Viberti, P Ruggenenti
1Mario Negri Institute for Pharmacological Research; Ospedali Riuniti di Bergamo, Italy.
The American Journal of Physiology
|October 1, 1990
Summary
Acute hyperglycemia significantly increases glomerular filtration rate (GFR) in diabetic nephropathy patients. This effect is linked to increased ultrafiltration coefficient and membrane permeability, not altered renal plasma flow.
Area of Science:
- Nephrology
- Diabetology
- Renal Physiology
Background:
- Diabetic nephropathy is a major complication of diabetes mellitus.
- Understanding the impact of glycemic control on kidney function is crucial for managing diabetic kidney disease.
Purpose of the Study:
- To investigate the acute effects of hyperglycemia on glomerular function in patients with established diabetic nephropathy.
- To determine the specific determinants of glomerular filtration rate (GFR) affected by elevated blood glucose levels.
Main Methods:
- Utilized hyperglycemic and euglycemic clamp techniques in seven insulin-dependent diabetic patients with overt nephropathy.
- Measured glomerular filtration rate (GFR) and renal plasma flow under both glycemic conditions.
- Assessed fractional clearances of neutral dextrans of varying molecular sizes to analyze glomerular membrane properties.
- Employed a theoretical model to interpret macromolecule transport through the glomerular membrane.
Main Results:
- Glomerular filtration rate (GFR) was significantly higher during acute hyperglycemia compared to euglycemia (35.0 +/- 15.5 vs. 21.4 +/- 10.3 ml.min-1.1.73 m-2, P < 0.01).
- Renal plasma flow did not show a significant change between hyperglycemic and euglycemic states.
- Hyperglycemia increased the sieving coefficients for small dextran molecules (28-40 A radius), indicating enhanced permeability.
- Fractional clearances of large macromolecules (> 44 A) remained unchanged.
- Theoretical analysis suggested an increase in the ultrafiltration coefficient (Kf) and membrane permeability to small dextrans during hyperglycemia.
Conclusions:
- Acute hyperglycemia enhances glomerular filtration rate in patients with severe diabetic nephropathy and renal failure.
- The observed increase in GFR is primarily attributed to increased ultrafiltration coefficient and enhanced glomerular membrane permeability to smaller molecules.
- These findings may not be generalizable to the early stages of diabetic nephropathy due to the patient cohort's severe renal impairment and hypertension.