Glomerular response to hyperglycemia in human diabetic nephropathy

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.