AJP - Renal Physiology, Vol 259, Issue 4 545-F552, Copyright © 1990 by American Physiological Society
Glomerular response to hyperglycemia in human diabetic nephropathy
A. Remuzzi, G. Viberti, P. Ruggenenti, C. Battaglia, R. Pagni and G. Remuzzi
Mario Negri Institute for Pharmacological Research; Ospedali Riuniti di Bergamo, Italy.
We have studied the effect of acute hyperglycemia on glomerular function in
seven insulin-dependent diabetics with overt nephropathy during
hyperglycemic or euglycemic clamp. In all patients glomerular filtration
rate (GFR) was higher during hyperglycemia than during euglycemia (35.0 +/-
15.5 vs. 21.4 +/- 10.3 ml.min-1.1.73 m-2, P less than 0.01), whereas renal
plasma flow did not change significantly. To establish which determinant of
GFR is altered by hyperglycemia, fractional clearances of neutral dextrans
of graded molecular size were determined in both glycemic states, and data
were analyzed by a theoretical model of hindered transport of
macromolecules through a porous membrane. Hyperglycemia significantly
increased sieving coefficients of small dextran molecules (28-40 A in
radius), whereas fractional clearances of large macromolecules (greater
than 44 A) did not change. Theoretical analysis suggested that the
ultrafiltration coefficient (Kf) and membrane permeability to small
dextrans (less than 40 A) increased in hyperglycemia in respect to
euglycemia. Because these results have been obtained in patients with
severe renal failure and hypertension, our conclusions do not necessarily
apply to the early phase of diabetic nephropathy.
