Summary
The mammalian glomerular capillary wall normally restricts the transmural passage of plasma proteins while offering little resistance to the filtration of water and small solutes. The basis for this selectivity has been explored extensively in recent years, through clearance measurements of endogenous (mainly albumin, transferrin, and immunoglobulins) and exogenous (horseradish peroxidase) proteins, and a variety of nonprotein polymers such as dextrans and polyvinylpyrrolidone. In conjunction with efforts to localize particulate and soluble tracers by high resolution ultrastructural techniques, such measurements have now made it possible to define the determinants of the glomerular filtration of macromolecules in terms of discrete structural barriers as well as such biophysical influences as hemodynamics and the molecular size- and charge-selective characteristics of the capillary wall.
These experimental approaches have been aided greatly by the development of theoretical models that enable investigators to describe macromolecular filtration in terms of hydrodynamic principles applied to isoporous membranes. Although the initial models failed to consider the important role of membrane fixed negative-charge characteristics in influencing protein filtration, this shortcoming has led to the recent introduction of a theoretical model that also takes this factor into consideration. The aim of this brief review is to summarize these various theoretical approaches to the understanding of glomerular permselectivity and, wherever possible, to cite specific tests of these theories based on experimental studies in humans and animals.
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References
Anderson, J.L., Quinn, J.A. 1974. Restricted transport in small pores. A model for steric exclusion and hindered particle motion.Biophys. J. 14:130–150
Arturson, G., Groth, T., Grotte, G. 1971. Human glomerular membrane porosity and filtration pressure: Dextran clearance data analyzed by theoretical models.Clin. Sci. 40:137–158
Bennett, C.M., Glassock, R.J., Chang, R.L.S., Deen, W.M., Robertson, C.R., Brenner, B.M. 1976. Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using dextran sulfate.J. Clin. Invest. 57:1287–1294
Blau, E.B., Haas, D.E. 1973. Glomerular sialic acid and proteinuria in human renal disease.Lab. Invest. 28:477–481
Blau, E.B., Michael, A.F. 1972. Rat glomerular glycoprotein composition and metabolism in aminonucleoside nephrosis.Proc. Soc. Expt. Biol. Med. 141:164–172
Bohrer, M.P., Baylis, C., Humes, H.D., Glassock, R.J., Robertson, C.R., Brenner, B.M. 1978. Permselectivity of the glomerular capillary wall. Facilitated filtration of circulating polycations.J. Clin. Invest. 61:72–78
Bohrer, M.P., Baylis, C., Robertson, C.R., Brenner, B.M. 1977. Mechanism of the puromycin-induced defects in the transglomerular passage of water and macromolecules.J. Clin. Invest. 60:152–161
Bohrer, M.P., Deen, W.M., Robertson, C.R., Brenner, B.M. 1977. Mechanism of angiotensin II — induced proteinuria in the rat.Am. J. Physiol. 233:F13-F21
Bohrer, M.P., Deen, W.M., Robertson, C.R., Troy, J.L., Brenner, B.M. 1979. Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall.J. Gen. Physiol. 74:583–593
Brenner, B.M., Baylis, C., Deen, W.M. 1976. Transport of molecules across renal glomerular capillaries.Physiol. Rev. 56:502–534
Buerkert, J.E., Mor, J., Murray, B.N., Robson, A.M. 1976. Glomerular permeability in disease: A proposed role of the glomerular epithelial cell.(Abstr.) Proc. Am. Soc. Nephrol. 9:69
Carrie, B.J., Myers, B.D. 1980. Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy.Kidney Int. 19:669–676
Caulfield, J.P., Farquhar, M.G. 1976. Distribution of anionic sites in normal and nephrotic glomerular basement membranes.(Abstr.) J. Cell Biol. 70:92a
Chang, R.L.S., Deen, W.M., Robertson, C.R., Brenner, B.M. 1975. Permselectivity of the glomerular capillary wall: III. Restricted transport of polyanions.Kidney Int. 8:212–218
Chang, R.L.S., Deen, W.M., Robertson, C.R., Bennett, C.M., Glassock, R.J., Brenner, B.M. 1976. Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran.J. Clin. Invest 57:1272–1286
Chang, R.L.S., Robertson, C.R., Deen, W.M., Brenner, B.M. 1975. Permselectivity of the glomerular capillary wall to macromolecules: I. Theoretical considerations.Biophys. J. 15:861–886
Chang, R.L.S., Ueki, I.F., Troy, J.L., Deen, W.M., Robertson, C.R., Brenner, B.M. 1975. Permselectivity of the glomerular capillary wall to macromolecules: II. Experimental studies in rats using neutral dextran.Biophys. J. 15:887–906
De Bats, A., Gordon, A.H., Rhodes, E.L. 1974. Variations in glomerular sialic acid content in diabetes and as the result of aging.Clin. Sci. Molec. Med. 47:93–95
Deen, W.M., Bohrer, M.P., Brenner, B.M. 1979. Macromolecule transport across glomerular capillaries: Application of pore theory.Kidney Int. 16:353–365
Deen, W.M., Bridges, C.R. 1982. Addenda and correction. Molecular charge of horseradish peroxidase.Am. J. Physiol. 242:F750
Deen, W.M., Robertson, C.R., Brenner, B.M. 1972. A model of glomerular ultrafiltration in the rat.Am. J. Physiol. 223:1178–1183
Deen, W.M., Satvat, B., Jamieson, J.M. 1980. Theoretical model for glomerular filtration of charged solutes.Am. J. Physiol. 238:F126-F139
Deen, W.M., Satvat, B. 1981. Determinants of the glomerular filtration of proteins.Am. J. Physiol. 241:F162-F170
Dubois, R., Decoodt, P., Gassèe, J.P., Verniory, A., Lambert, P.P. 1975. Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data: I. A mathematical model.Pfluegers Arch. 356:299–316
Eisenbach, G.M., Van Liew, J.B., Boylan, J.W. 1975. Effect of angiotensin on the filtration of protein in the rat kidney: A micropuncture study.Kidney Int. 8:80–87
Galaske, R.G., Baldamus, C.A., Stolte, H. 1978. Plasma protein handling in the rat kidney: Micropuncture experiments in the acute heterologous phase of anti-GBM nephritis.Pfluegers Arch. 375:269–277
Gassèe, J.P. 1973. Effect of acetylcholine on glomerular sieving of macromolecules.Pfluegers Arch. 342:239–254
Gassèe, J.P., Dubois, R., Staroukine, M., Lambert, P.P. 1976. Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data: III. The effects of angiotensin II.Pfluegers Arch. 367:15–24
Hardwicke, J., Cameron, J.S., Harrison, J.F., Hulme, B., Soothill, J.F. 1970.In: Proteins in Normal and Pathological Urine. Y. Manuel, J.P. Revillard, and H. Betuel, editors. pp. 111–152. University Press, Baltimore
Huss, R.E., Marsh, D.J., Kalaba, R.E. 1975. Two models of glomerular filtration rate and renal blood flow in the rat.Ann. Biomed. Eng. 3:72–99
Lambert, P.P., Aeikens, B., Bohle, A., Hanus, F., Pegoff, S., Van Damme, M. 1982. A network model of glomerular function.Microvasc. Res. 23:99–128
Lambert, P.P., Dubois, R., Decoodt, P., Gassèe, J.P., Verniory, A. 1975. Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data: II. A physiological study in the normal dog.Pfluegers Arch. 359:1–22
Leber, P.D., Marsh, D.J. 1970. Micropuncture study of concentration and fate of albumin in rat nephron.Am. J. Physiol. 219:353–363
Lui, S., Kalant, N. 1974. Carbohydrate of the glomerular basement membrane in normal and nephrotic rats.Exp. Molec. Pathol. 21:52–62
Michael, A.F., Blau, E., Vernier, R.L. 1970. Glomerular polyanion: Alteration in aminonucleoside nephrosis.Lab. Invest. 23:649–657
Oken, D.E., Cotes, S.C., Mende, C.W. 1972. Micropuncture study of tubular transport of albumin in rats with aminonucleoside nephrosis.Kidney Int. 1:3–11
Olsen, J.L., Rennke, H.G., Venkatachalam, M.A. 1981. Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats.Lab. Invest. 44:271–279
Pappenheimer, J.R. 1953. Passage of molecules through capillary walls.Physiol. Rev. 33:387–423
Pappenheimer, J.R., Renkin, E.M., Borrero, L.M. 1951. Filtration, diffusion and molecular sieving through peripheral capillary membranes. A contribution to the pore theory of capillary permeability.Am. J. Physiol. 167:13–46
Renkin, E.M., Gilmore, J.P. 1973.In: Handbook of Physiology, Section 8: Renal Physiology. J. Orloff and R.W. Berliner, editors. pp. 185–248. American Physiological Society, Washington
Rennke, H.G., Cotran, R.S., Venkatachalam, M.A. 1975. Role of molecular charge in glomerular permeability: Tracer studies with cationized ferritins.J. Cell Biol. 67:638–646
Rennke, H.G., Patel, Y., Venkatachalam, M.A. 1978. Glomerular filtration of proteins: Clearance of anionic, neutral, and cationic horseradish peroxidase in the rat.Kidney Int. 13:278–288
Rennke, H.G., Venkatachalam, M.A. 1977. Glomerular permeability:In vivo tracer studies with polyanionic and polycationic ferritins.Kidney Int. 11:44–53
Rennke, H.G., Venkatachalam, M.A. 1979. Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat.J. Clin. Invest. 63:713–717
Robson, A.M., Giangiacomo, J., Keinstra, R.A., Naqvi, S.T., Ingelfinger, J.R. 1974. Normal glomerular permeability and its modification by minimal change nephrotic syndrome.J. Clin. Invest. 54:1190–1199
Smith, F.G., III, Deen, W.M. 1980. Electrostatic doublelayer interactions for spherical colloids in cylindrical pores.J. Colloid Interface Sci. 78:444–465
Verniory, A., Dubois, R., Decoodt, P., Gassèe, J.P., Lambert, P.P. 1973. Measurement of the permeability of biological membranes: Application to the glomerular wall.J. Gen. Physiol. 62:489–507
Winetz, J.A., Robertson, C.R., Golbetz, H.V., Carrie, B.J., Salyer, W.R., Myers, B.D. 1981. The nature of the glomerular injury in minimal change and focal sclerosing glomerulopathies.Am. J. Kidney Dis. 1:91–98
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Deen, W.M., Bridges, C.R. & Brenner, B.M. Biophysical basis of glomerular permselectivity. J. Membrain Biol. 71, 1–10 (1983). https://doi.org/10.1007/BF01870670
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DOI: https://doi.org/10.1007/BF01870670