Ultrafiltration in single isolated human glomeruli

Abstract

To determine the ultrafiltration properties of human glomeruli, we induced filtration in vitro and estimated the glomerular ultrafiltration coefficient, K(f) or LpA, and the glomerular capillary hydraulic conductivity, Lp, in single glomeruli from 17 human kidneys retrieved for allotransplantation. Cadaver donors ranged in age from 2 to 46 years. Filtration was induced in individual isolated glomeruli by abruptly lowering the protein concentration of the medium surrounding the glomerulus to produce a transcapillary oncotic gradient. The events which occurred were recorded on videotape for analysis. K(f) was calculated from the maximum rate of glomerular swelling during filtration. Initial glomerular diameter for the individuals studied ranged from 146 ± 2 μm (age, 2 years), to 292 ± 6 μm (age, 42 years). K(f) ranged from 5.1 ± 0.8 to 30.7 ± 3.0 nl/min·mm Hg and varied directly with donor age and glomerular size. The glomerular filtering area was estimated from the formula A = 3πD2 and from morphometrically measured basement membrane surface density. Lp was calculated from Lp = K(f)/A. Lp using A = 3πD2 (Lp(D)) averaged 3.7 ± 0.2 μl/min·mm Hg·cm2. To compare the hydraulic conductivity of glomeruli from children and adults, Lp was also calculated using the total basement membrane area derived from measured surface density (Lp(S)). Lp(S) averaged 1.5 ± 0.1 μl/min·mm Hg·cm2 (N = 17) and was not significantly different in children and adults suggsting that the increase in K(f) during maturation from 2 years of age to adulthood is accomplished by an increase in capillary surface area rather than by a major change in the hydraulic conductivity of the capillary wall. With an average K(f) for children and adults of about 6 and 17 nl/min·mm Hg·cm2, respectively, normal GFR may be maintained with a mean ultrafiltration pressure of about 4 mm Hg. The direct relationship between K(f) and calculated filtering area per glomerulus may be used to define the normal filtration characteristics of human glomeruli.