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. 1969 Aug 1;130(2):381–399. doi: 10.1084/jem.130.2.381

GLOMERULAR PERMEABILITY

ULTRASTRUCTURAL STUDIES IN EXPERIMENTAL NEPHROSIS USING HORSERADISH PEROXIDASE AS A TRACER

M A Venkatachalam 1, Morris J Karnovsky 1, Ramzi S Cotran 1
PMCID: PMC2138683  PMID: 5795100

Abstract

Wistar/Furth rats were made nephrotic by daily administration of amino-nucleoside of puromycin, and the ultrastructural localization of horseradish peroxidase (mol wt 40,000) in the renal glomerulus was studied from 1 min to 20 hr after intravenous injection of the tracer. In control rats, peroxidase permeated the endothelial fenestrae, the basement membrane, and the epithelial slits, and was present in tubular lumina. Nephrotic glomeruli showed relatively normal basement membranes, extensive fusion of foot processes with formation of "close" intercellular junctions, and large vacuoles and pockets in epithelial cells. On serial sections some of the epithelial vacuoles communicated on one side with the extracellular space overlying basement membrane, and on the other side with the urinary space. In nephrotic animals, peroxidase permeated the basement membrane and the close junctions, and was present in many of the vacuoles and pockets as early as 1 min after injection. Only small numbers of peroxidase-positive vacuoles remained in. epithelial cells 1 hr or more after injection of the tracer. It is suggested that the epithelial pockets and vacuoles form pathways across which leaking proteins can be transferred across the epithelium into the urinary space. Epithelial vacuoles may also be absorption droplets designed to "conserve" leaking proteins, but this function was not prominent in our experiments with peroxidase.

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Selected References

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

  1. CHINARD F. P., LAUSON H. D., EDER H. A., GREIF R. L., HILLER A. A study on the mechanism of proteinuria in patients with the nephrotic syndrome. J Clin Invest. 1954 Apr;33(4):621–628. doi: 10.1172/JCI102933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cotran R. S., Karnovsky M. J., Goth A. Resistance of Wistar-Furth rats to the mast cell-damaging effect of horseradish peroxidase. J Histochem Cytochem. 1968 May;16(5):382–383. doi: 10.1177/16.5.382. [DOI] [PubMed] [Google Scholar]
  3. FARQUHAR M. G., PALADE G. E. Glomerular permeability. II. Ferritin transfer across the glomerular capillary wall in nephrotic rats. J Exp Med. 1961 Nov 1;114:699–716. doi: 10.1084/jem.114.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FARQUHAR M. G., VERNIER R. L., GOOD R. A. An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus. J Exp Med. 1957 Nov 1;106(5):649–660. doi: 10.1084/jem.106.5.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FARQUHAR M. G., VERNIER R. L., GOOD R. A. Studies on familial nephrosis. II. Glomerular changes observed with the electron microscope. Am J Pathol. 1957 Jul-Aug;33(4):791–817. [PMC free article] [PubMed] [Google Scholar]
  6. FARQUHAR M. G., WISSIG S. L., PALADE G. E. Glomerular permeability. I. Ferritin transfer across the normal glomerular capillary wall. J Exp Med. 1961 Jan 1;113:47–66. doi: 10.1084/jem.113.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FELDMAN J. D., FISHER E. R. Renal lesions of aminonucleoside nephrosis as revealed by electron microscopy. Lab Invest. 1959 Mar-Apr;8(2):371–385. [PubMed] [Google Scholar]
  8. FRENK S., ANTONOWICZ I., CRAIG J. M., METCOFF J. Experimental nephrotic syndrome induced in rats by aminonucleoside; renal lesions and body electrolyte composition. Proc Soc Exp Biol Med. 1955 Jul;89(3):424–427. doi: 10.3181/00379727-89-21833. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Graham R. C., Jr, Karnovsky M. J. The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique. J Histochem Cytochem. 1966 Apr;14(4):291–302. doi: 10.1177/14.4.291. [DOI] [PubMed] [Google Scholar]
  11. HARDWICKE J., SQUIRE J. R. The relationship between plasma albumin concentration and protein excretion in patients with proteinuria. Clin Sci. 1955 Aug;14(3):509–530. [PubMed] [Google Scholar]
  12. VERNIER R. L., PAPERMASTER B. W., GOOD R. A. Aminonucleoside nephrosis. I. Electron microscopic study of the renal lesion in rats. J Exp Med. 1959 Jan 1;109(1):115–126. doi: 10.1084/jem.109.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. WALLENIUS G. [Renal clearance of dextran as a measure of glomerular permeability]. Acta Soc Med Ups Suppl. 1954 Apr 8;59(4):1–91. [PubMed] [Google Scholar]
  14. WILSON S. G., HACKEL D. B., HORWOOD S., NASH G., HEYMANN W. Aminonucleoside nephrosis in rats. Pediatrics. 1958 Jun;21(6):963–973. [PubMed] [Google Scholar]

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