Glomerular Filtration Of Macromolecules Research Articles

Glomerular filtration of macromolecules: normal mechanisms and the pathogenesis of proteinuria.

Glomerular filtration of macromolecules: normal mechanisms and the pathogenesis of proteinuria.

A High-Powered View of the Filtration Barrier

Multiphoton excitation fluorescence microscopy is a powerful noninvasive imaging technique for the deep optical sectioning of living tissues. Its application in several intact tissues is a significant advance in our understanding of organ function, including renal pathophysiological mechanisms. The glomerulus, the filtering unit in the kidney, is one good example of a relatively inaccessible and complex structure, with cell types that are otherwise difficult to study at high resolution in their native environment. In this article, we address the application, advantages, and limitations of this imaging technology for the study of the glomerular filtration barrier and the controversy it recently generated regarding the glomerular filtration of macromolecules. More advanced and accurate multiphoton determinations of the glomerular sieving coefficient that are presented here dismiss previous claims on the filtration of nephrotic levels of albumin. The sieving coefficient of 70-kD dextran was found to be around 0.001. Using a model of focal segmental glomerulosclerosis, increased filtration barrier permeability is restricted only to areas of podocyte damage, consistent with the generally accepted role of podocytes and the glomerular origin of albuminuria. Time-lapse imaging provides new details and important in vivo confirmation of the dynamics of podocyte movement, shedding, replacement, and the role of the parietal epithelial cells and Bowman's capsule in the pathology of glomerulosclerosis.

Development of human renal function: reference intervals for 10 biochemical markers in fetal urine

Evaluation of fetal renal function by analysis of fetal urine sampled in utero may improve perinatal care after a prenatal diagnosis of bilateral obstructive uropathy. We provide reference intervals for 10 fetal urinary compounds and examine their variation with gestational age. Forty-one fetuses with bilateral obstructive uropathy (urine sampled between 20 and 38 weeks of gestational age) had normal, healthy values for serum creatinine (< or = 50 mumol/L) at ages 1-2 years. These cases were thus assumed to represent a reasonable approximation to healthy values. Sodium and beta 2-microglobulin concentrations significantly decreased with gestational age; calcium, ammonia, and creatinine significantly increased; glucose, phosphorus, chloride, urea, and total protein concentrations did not vary. Our results provide reference values for prenatal evaluation of fetal renal function and suggest that glomerular filtration of macromolecules and tubular reabsorption of glucose and phosphorus are mature by 20 weeks of gestation, whereas tubular reabsorption of sodium and beta 2-microglobulin increases progressively during the second half of gestation.

Theoretical effects of network structure on glomerular filtration of macromolecules.

A parallel network model was developed to examine the effects of a distribution of capillary lengths on the filtration of macromolecules by the glomerulus. When networks having different distributions of capillary lengths (but similar values of single nephron glomerular filtration rate) were compared, the filtrate-to-plasma concentration ratio (theta s) for neutral macromolecules was found to increase as the vessel lengths became less uniform. Because anatomical studies have demonstrated that the glomerulus is in fact a heterogeneous network, this implies that the conventional modeling assumption of identical capillaries in parallel leads to an overestimation of effective pore sizes. However, simulations employing various pore-size distributions demonstrated that the expected errors in estimating membrane-pore parameters are generally negligible. Furthermore, the dependence of theta s on hemodynamic inputs such as glomerular plasma flow rate and transmembrane hydraulic pressure difference was insensitive to the assumed distribution of capillary lengths. We conclude that models based on dimensionally uniform capillary networks remain valid for interpreting clearance data for macromolecules.

Ultrastructure of the glomerular basement membrane, as visualized by lanthanum.

SummaryCortical tissues from the kidneys of rats were infused with a suspension of lanthanum hydroxide, or were placed in fixatives containing lanthanum to visualize intermolecular spaces in the glomerular basement membrane. Lanthanum particles were seen in aggregates throughout the basement membrane. The diameter of the aggregates varied between 20 and 200 A. The diameter of the majority of aggregates ranged from 40 to 75 A. Aggregates with diameters greater than 150 A were located mainly in the lamina rara interna, less in the lamina rara externa.It is concluded that the basement membrane is a random porous molecular filter and the lamina densa is the rate limiting structure in the glomerular filtration of macromolecules.