Human Glomerular Membrane Porosity and Filtration Pressure: Dextran Clearance Data Analysed by Theoretical Models

Abstract

1. The renal clearance of dextran of different molecular sizes has been measured in normal humans from 6 days to 61 years of age. Gel chromatography of dextran has been used for determination of molecular weight distribution.2. Information about the functional ultrastructure of the glomerular membrane has been deduced from the experimental clearance data in the light of theoretical models. The glomerular membrane was here visualized as a gel filter, localized in the basement membrane. The physical analogue of this membrane was interpreted as a somewhat heteroporous structure of quite well defined pore sizes: one system of smaller pores in the range of 20-28 A radius and an additional system of larger pores of radii up to 80 A. These larger pores are quite few in number with an approximate ratio of one large pore per 10 OOO small pores.3. The values obtained for the transglomerular pressure difference were low, about 1 cm of water or less. This supports the concept that tubular reabsorption may be the rate limiting factor in the process of urine formation and may also control the glomerular filtration rate.4. The changes of the dextran clearance with ageing found in this investigation may be explained by an increase of the pore radii of the glomerular membrane and a concomitant decrease of the transglomerular pressure difference.The sieving effect of the glomerular membrane has in electron microscopic studies been attributed to three different sites : fenestrae between endothelial cells, the basement membrane, and/or slits between epithelial cells in the urine space (Fig. 1). The functional ultrastructure of the glomerular membrane has also been evaluated by studying the transport of molecules of different sizes into urine.In the present study dextran was used as a test substance in order to investigate glomerular permeability, i.e. glomerular membrane porosity and fltration pressure. The high precision of

Normal Glomerular Permeability and Its Modification by Minimal Change Nephrotic Syndrome

“…Traditionally this structure has been considered to behave as a semipermeable membrane containing cylindrical pores of [35][36][37][38][39][40][41][42] A radius or rectilinear slits of half-width 36 A (5). However, if the membrane does contain functional pores, it may be more heteroporous than originally suggested (6), and although these experiments suggest that the basement membrane contains pores, such pores have never been demonstrated. An alternate view conceives the GBM as a hydrated gel with glomerular filtration occurring by diffusion (7).…”

Functional and Morphologic Maturation of the Superficial Nephrons RELATIONSHIP TO TOTAL KIDNEY FUNCTION

“…Evidence that glomerular size need not correlate linearly with the capacity for filtration, at least in the immature kidney, can be derived from the work of Arturson et al (46), who demonstrated a significant increase in the permeability of the glomerular capillary membrane with age. Furthermore, surface area available for or used in the process of filtration need not be a function of the glomerular volume, and might vary during development.…”

“…During the following 15 days Puf increased to 13.9 cm H20 (another 50%), while SNGFR rose about 500%. Since the permeability of the glomerular membrane increases as a function of age (46) Pur at the foremost end of the glomerular capillary, if anything, will tend to overestimate the mean Puf more in the older than in the younger animals. Or stated in another way, the increase in mean PuR over the period covered by the study most likely was smaller than suggested by our measurements.…”

Permselectivity of of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran.

“…Curves are shown for NSN rats and for a group of non-nephritic control rats studied previously (9). Over the range of effective dextran radii studied, 14F- 12 10 Si(cm) FIGURE 3 (A) The relationship between ro, the pore radius, and effective dextran radius, a, for NSN rats and non-nephritic normal control rats. (B) The relationship between S'/l, ratio of the total pore area to pore length, and effective dextran radius, a, for NSN rats and non-nephritic normal control rats.…”