Glomerular function in advanced human diabetic nephropathy

Abstract

Intrinsic membrane properties of the glomerular capillary wall were evaluated in 20 diabetic patients, who had heavy proteinuria and reduced GFR, and in 15 healthy control subjects. The glomerular sieving coefficients were determined for narrow dextran fractions with molecular radii between 20 and 64 A. GFR determinants were directly measured or indirectly estimated. These quantities were then subjected to a theoretical analysis based upon (1) a mathematical model of glomerular ultrafiltration and (2) a pore model of transmembrane solute transport. The results indicated that in patients with diabetic nephropathy and glomerular ultrafiltration coefficient (0.02 vs. 0.16 ml . sec-1 . mm Hg-1 . 1.73m-2), effective pore area-to-pore length (2.6 x 10(6) vs. 20.0 x 10(6) cm), and mean pore radius (56.8 vs. 58.0 A) are all reduced relative to normal control subjects. It is suggested that (1) hypofiltration in advanced diabetic nephropathy results, in part, from reduction of the surface area available for filtration, while (2) proteinuria is a consequence of either loss of electrostatic barrier function, of isolated focal disruptions within the glomerular filtration barrier, or a combination thereof.

Angiotensin converting enzyme inhibition ameliorates glomerular filtration of macromolecules and water and lessens glomerular injury in the rat.

“…The pattern of glomerular sieving curve alteration found in humans (9) and by our present study in the rat appears unique of enalapril treatment. We found that 0 of small (radius < 30 A) and large test macromolecules (radius > 50 A) were significantly reduced while in the majority of other studies, performed in animals (23,36,37) and in humans (27,38,39), restoration of glomerular selective function was invariably associated with a reduction in 0 of largest dextran molecules, as in the present study, but with a concomitant increase in 0 of small dextran molecules.…”

Structural-functional relationships in diabetic nephropathy.

“…It is known that the microalbuminuria of diabetic patients without clinical nephropathy (4,5) is reversible by the institution of short-term strict glycemic control (5), whereas in diabetic patients with overt proteinuria, fractional IgG and albumin clearances continue to increase and GFR continues to decrease despite 6 mo of strict glycemic control (41). It is also known that the onset of overt proteinuria ushers in the development of a progressive deterioration in the macromolecular permselective characteristics of the glomerular barrier (38,42). It is, therefore, reasonable to consider that microalbuminuria and overt clinical proteinuria in diabetes reflect different pathogenetic processes.…”

Immune Complex Disease Complicating Diabetic Glomerulosclerosis

“…Proteinuria, an early manifesta tion of diabetic renal disease, reflects an alteration in per meability of the glomerular capillary wall [22,23]. Such alteration develops after a variable period of time, usually many years after the onset of diabetes [24,25], and morphologically there is diffuse thickening of the GBM.…”