Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1974 Nov;54(5):1190–1199. doi: 10.1172/JCI107862

Normal Glomerular Permeability and Its Modification by Minimal Change Nephrotic Syndrome

Alan M Robson 1,2, Joseph Giangiacomo 1,2, Randy A Kienstra 1,2, Saiyid T Naqvi 1,2, Julie R Ingelfinger 1,2
PMCID: PMC301666  PMID: 4417621

Abstract

It has been suggested that the glomerular basement membrane restricts the passage of large molecules only, the barrier to filtration of smaller molecules being at the level of the epithelial slit pore. This hypothesis was investigated by measuring glomerular permeability to 125I-labeled polydisperse polyvinyl pyrrolidone (PVP) in 16 children with idiopathic nephrotic syndrome (INS) and in 6 children of comparable age who had no evidence of renal disease. Studies were performed in the patients with INS before, during, and after treatment with steroids. PVP in blood and urine samples was separated according to molecular size by solumn chromatography, to permit the calculation of permeability to inert macromolecules of sizes ranging from 8,000 mol wt. In untreated INS, glomerular permeability to molecules > 40 Å was normal; permeability to smaller molecules was markedly reduced, frequently to 20% or less of normal. There was an average decrease in inulin clearance (Cin) of 24%. Glomerular permeability and Cin returned to normal in INS treated with steroids only when proteinuria disappeared. The results support the concept, derived from studies with ultrastructural tracers, that the final barrier to filtration may be at the level of the epithelial slit pore. Thus fusion of the epithelial foot processed with obliteration of the slit pores was associated with impaired passage of smaller molecules of PVP into the urine. Reversal of the pathologic abnormality resulted in return of permeability to normal. The decreased Cin seen in INS may not reflect true glomerular filtration rate, but may result from restricted passage of inulin molecules (mol wt 5,000) through the epithelial slit pore.

Full text

PDF
1190

Images in this article

1194Image
on p.1194
1195Image
on p.1195
1195Image
on p.1195

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ACKERS G. K. MOLECULAR EXCLUSION AND RESTRICTED DIFFUSION PROCESSES IN MOLECULAR-SIEVE CHROMATOGRAPHY. Biochemistry. 1964 May;3:723–730. doi: 10.1021/bi00893a021. [DOI] [PubMed] [Google Scholar]
  2. ANDERSON M. S., RECANT L. Fine structural alterations in the rat kidney following intraperitoneal bovine albumin. Am J Pathol. 1962 May;40:555–569. [PMC free article] [PubMed] [Google Scholar]
  3. Andrews P. The gel-filtration behaviour of proteins related to their molecular weights over a wide range. Biochem J. 1965 Sep;96(3):595–606. doi: 10.1042/bj0960595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arturson G., Groth T., Grotte G. Human glomerular membrane porosity and filtration pressure: dextran clearance data analysed by theoretical models. Clin Sci. 1971 Feb;40(2):137–158. doi: 10.1042/cs0400137. [DOI] [PubMed] [Google Scholar]
  5. BEATTIE J., CORCORAN A. C. Renal clearances of grass polysaccharide: observations on glomerular porosity and on the relation of this function to proteinuria in renal disease. J Clin Invest. 1952 May;31(5):445–450. doi: 10.1172/JCI102628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BERLYNE G. M., VARLEY H., NILWARANGKUR S., HOERNI M. ENDOGENOUS-CREATININE CLEARANCE AND GLOMERULAR-FILTRATION RATE. Lancet. 1964 Oct 24;2(7365):874–876. doi: 10.1016/s0140-6736(64)90735-4. [DOI] [PubMed] [Google Scholar]
  7. BRANDT J. L., FRANK R., LICHTMAN H. C. Normal hemoglobin clearances in chronic proteinuria. Proc Soc Exp Biol Med. 1950 Aug;74(4):863–865. doi: 10.3181/00379727-74-18071. [DOI] [PubMed] [Google Scholar]
  8. Brenner B. M., Troy J. L., Daugharty T. M. The dynamics of glomerular ultrafiltration in the rat. J Clin Invest. 1971 Aug;50(8):1776–1780. doi: 10.1172/JCI106667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. CHINARD F. P. Derivation of an expression for the rate of formation of glomerular fluid (GFR). Applicability of certain physical and physico-chemical concepts. Am J Physiol. 1952 Dec;171(3):578–586. doi: 10.1152/ajplegacy.1952.171.3.578. [DOI] [PubMed] [Google Scholar]
  10. Churg J., Habib R., White R. H. Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet. 1970 Jun 20;760(1):1299–1302. doi: 10.1016/s0140-6736(70)91905-7. [DOI] [PubMed] [Google Scholar]
  11. Deen W. M., Troy J. L., Robertson C. R., Brenner B. M. Dynamics of glomerular ultrafiltration in the rat. IV. Determination of the ultrafiltration coefficient. J Clin Invest. 1973 Jun;52(6):1500–1508. doi: 10.1172/JCI107324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Graham R. C., Jr, Karnovsky M. J. Glomerular permeability. Ultrastructural cytochemical studies using peroxidases as protein tracers. J Exp Med. 1966 Dec 1;124(6):1123–1134. doi: 10.1084/jem.124.6.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HALL V. The protoplasmic basis of glomerular ultrafiltration. Am Heart J. 1957 Jul;54(1):1–9. doi: 10.1016/0002-8703(57)90073-x. [DOI] [PubMed] [Google Scholar]
  14. Huang F., Hutton L., Kalant N. Molecular sieving by glomerular basement membrane. Nature. 1967 Oct 7;216(5110):87–88. doi: 10.1038/216087a0. [DOI] [PubMed] [Google Scholar]
  15. Imai M., Kokko J. P. Effect of peritubular protein concentration on reabsorption of sodium and water in isolated perfused proxmal tubules. J Clin Invest. 1972 Feb;51(2):314–325. doi: 10.1172/JCI106816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. JOACHIM G. R., CAMERON J. S., SCHWARTZ M., BECKER E. L. SELECTIVITY OF PROTEIN EXCRETION IN PATIENTS WITH THE NEPHROTIC SYNDROME. J Clin Invest. 1964 Dec;43:2332–2346. doi: 10.1172/JCI105107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jones D. B. Mucosubstances of the glomerulus. Lab Invest. 1969 Aug;21(2):119–125. [PubMed] [Google Scholar]
  18. Kalant N., Misra R. P., Manley R. S., Wilson J. Glomerular basement membrane in experimental nephrosis: x-ray diffraction and electrophoretic studies. Nephron. 1966;3(3):167–174. doi: 10.1159/000179473. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Lambert P. P., Verniory A., Gassee J. P., Ficheroulle P. Sieving equations and effective glomerular filtration pressure. Kidney Int. 1972 Sep;2(3):131–146. doi: 10.1038/ki.1972.83. [DOI] [PubMed] [Google Scholar]
  21. Lorentz W. B., Jr, Lassiter W. E., Gottschalk C. W. Renal tubular permeability during increased intrarenal pressure. J Clin Invest. 1972 Mar;51(3):484–492. doi: 10.1172/JCI106836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Michael A. F., Blau E., Vernier R. L. Glomerular polyanion. Alteration in aminonucleoside nephrosis. Lab Invest. 1970 Dec;23(6):649–657. [PubMed] [Google Scholar]
  23. Misra R. P., Berman L. B. Studies on glomerular basement membrane. 3. Effects of steroid on membrane chemistry and its protein permeability. Lab Invest. 1972 Jun;26(6):666–670. [PubMed] [Google Scholar]
  24. Misra R. P., Berman L. B. Studies on glomerular basement membrane. II. Isolation and chemical analysis of diseased glomerular basement membrane. Lab Invest. 1968 Feb;18(2):131–138. [PubMed] [Google Scholar]
  25. Misra R. P., Kalant N. Glomerular basement membrane in experimental nephrosis: chemical composition. Nephron. 1966;3(2):81–102. [PubMed] [Google Scholar]
  26. Smith H. W., Finkelstein N., Aliminosa L., Crawford B., Graber M. THE RENAL CLEARANCES OF SUBSTITUTED HIPPURIC ACID DERIVATIVES AND OTHER AROMATIC ACIDS IN DOG AND MAN. J Clin Invest. 1945 May;24(3):388–404. doi: 10.1172/JCI101618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. VERNIER R. L., WORTHEN H. G., GOOD R. A. The pathology of the nephrotic syndrome. J Pediatr. 1961 May;58:620–639. doi: 10.1016/s0022-3476(61)80113-3. [DOI] [PubMed] [Google Scholar]
  28. Venkatachalam M. A., Cotran R. S., Karnovsky M. J. An ultrastructural study of glomerular permeability in aminonucleoside nephrosis using catalase as a tracer protein. J Exp Med. 1970 Dec 1;132(6):1168–1180. doi: 10.1084/jem.132.6.1168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Venkatachalam M. A., Karnovsky M. J., Cotran R. S. Glomerular permeability. Ultrastructural studies in experimental nephrosis using horseradish peroxidase as a tracer. J Exp Med. 1969 Aug 1;130(2):381–399. doi: 10.1084/jem.130.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Venkatachalam M. A., Karnovsky M. J., Fahimi H. D., Cotran R. S. An ultrastructural study of glomerular permeability using catalase and peroxidase as tracer proteins. J Exp Med. 1970 Dec 1;132(6):1153–1167. doi: 10.1084/jem.132.6.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. WHITE R. P., SAMSON F. E., Jr Determination of inulin in plasma and urine by use of anthrone. J Lab Clin Med. 1954 Mar;43(3):475–478. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES