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H V Golbetz

Publications and source records attributed to H V Golbetz.

4 recordsLinked to original sources

Mechanisms of proteinuria in diabetic nephropathy. II. A study of the size-selective glomerular filtration barrier.

We evaluated the size-selective properties of the glomerular barrier in 30 patients in whom diabetic nephropathy was associated with urinary IgG losses. Neutral dextrans of graded size were used to characterize glomerular membrane-pore structure. A fractional IgG clearance (relative to freely permeable inulin) smaller or greater than 0.001 was used to distinguish patients with minor (group 1, N = 14) and major (group 2, N = 16) urinary IgG leakage, respectively. Fractional clearances of dextrans (theta D) of smaller size (radii 20-40 A) were similar, but those of larger dextrans (radii 42-60 A) were elevated in group 2 relative to group 1 patients. When plotted on log-normal probability coordinates, the correlation between theta D and radius in healthy subjects is linear, suggesting that glomerular pores form one population with a normal distribution. In diabetic nephropathy with urinary IgG leakage, however, theta D for large molecules was elevated and departed from linearity, suggesting a bimodal pore size distribution within the glomerular membrane. A pore model of solute transport revealed (1) the upper pore mode was highly permeable to large dextrans equivalent in size to IgG and (2) the fraction of glomerular filtrate permeating the large pores was greater in group 2 than in group 1 patients with diabetic nephropathy, 6% versus 3%, respectively. We conclude that urinary IgG leakage in diabetic nephropathy is determined by the development of a subpopulation of enlarged pores. The magnitude of urinary IgG losses appears to be a function of the membrane area-fraction occupied by the enlarged pores.

Cell Membrane↗

Glomerular function in advanced human diabetic nephropathy.

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.

Adult↗

The nature of the glomerular injury in minimal change and focal sclerosing glomerulopathies.

Glomerular barrier function was evaluated in 12 healthy human volunteers and in 16 proteinuric patients in whom the nephrotic syndrome was associated with alteration of glomerular epithelial cells alone (minimal change nephropathy [MCN]) or in combination with focal glomerular sclerosis (FGS). We determined the glomerular sieving coefficient for each of nine narrow dextran fractions (Einstein Stoke radius [ESR] = 30 to 46 A), and directly measured, or indirectly estimated, values for the determinants of glomerular ultrafiltration. These quantities were then subjected to analysis based on an hydrodynamic theory of solute transport through an isoporous membrane. The results indicate that relative to normal subjects, effective pore radius is reduced from 59 to 55 and 53 A in McN and FGS, respectively; while the ratio, pore area to pore length (a measure of pore density) is correspondingly reduced from 21.7 X 10(6) to 10.1 X 10(6) and 4.7 X 10(6) cm. respectively, We suggest that collapse of the anionic glomerular membrane matrix in these proteinuric disorders may lead to pore shrinkage and reduced pore density, but that reduced electrostatic repulsion of anionic albumin (ESR = 36 A) facilitates its permeation into Bowman's space. The qualitatively similar disorder of glomerular barrier function in MCN and FGS is consistent with a unitary pathogenesis, but may represent a nonspecific response to depletion of glomerular polyanion.

Adolescent↗