Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1980 Feb;98(2):339–356.

Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. II. Ultrastructural studies.

W K Bolton, B C Sturgill
PMCID: PMC1903409  PMID: 7355986

Abstract

Increased protein filtration and work overload have been proposed to account for the development of glomerular sclerosis in old rats. Sprague-Dawley rat kidneys were examined ultrastructurally from birth through 24 months of age to further delineate pathogenetic factors. There was progressive thickening of all basement membranes with lamination, intramembranous pseudolinear deposits, and degeneration. The glomerular basement membrane (GBM) was 1300 A at birth and increased to 4800 A by 24 months of age. GBM thickening correlated very closely with age (r = 0.90, P less than 0.001), correlated roughly with mesangial sclerosis, but did not correlate at all with proteinuria. Obliteration of podocytes and degenerative changes in the cytoplasm occurred in all cell types and was present in both proteinuric and nonproteinuric rats. These findings suggest that the lesion of spontaneous glomerular sclerosis of aging rats results not from proteinuria but from the natural process of abiotrophic involution. Further, this lesion is but a more obvious indicator of the alterations occurring simultaneously in other portions of the kidney.

Full text

PDF
339

Images in this article

354Figure 5
on p.354
351Figure 1
on p.351
355Figure 6
on p.355
356Figure 7
on p.356
352Figure 2
on p.352
352Figure 3
on p.352
353Figure 4
on p.353

Selected References

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

  1. ADDIS T., MARMORSTON J., GOODMAN H. C., SELLERS A. L., SMITH M. Effect of adrenalectomy on spontaneous and induced proteinuria in the rat. Proc Soc Exp Biol Med. 1950 May;74(1):43–46. doi: 10.3181/00379727-74-17803. [DOI] [PubMed] [Google Scholar]
  2. ASHWORTH C. T., RDMANN R. R., ARNOLD N. J. Age changes in the renal basement membrane in rats. Am J Pathol. 1960 Feb;36:165–179. [PMC free article] [PubMed] [Google Scholar]
  3. BERG B. N., SIMMS H. S. Nutrition and longevity in the rat. II. Longevity and onset of disease with different levels of food intake. J Nutr. 1960 Jul;71:255–263. [PubMed] [Google Scholar]
  4. Bennett C. M., Glassock R. J., Chang R. L., Deen W. M., Robertson C. R., Brenner B. M., Troy J. L., ueki I. R., Rasmussen B. Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using dextran sulfate. J Clin Invest. 1976 May;57(5):1287–1294. doi: 10.1172/JCI108396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berg B. N. Effect of thyroxine on spontaneous nephrosis in the rat. Proc Soc Exp Biol Med. 1966 Jan;121(1):198–203. doi: 10.3181/00379727-121-30736. [DOI] [PubMed] [Google Scholar]
  6. Bolton W. K., Benton F. R., Maclay J. G., Sturgill B. C. Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. I. Lesions associated with mesangial IgM deposits. Am J Pathol. 1976 Nov;85(2):277–302. [PMC free article] [PubMed] [Google Scholar]
  7. Bolton W. K., Benton F. R., Sturgill B. C. Autoimmune glomerulotubular nephropathy in mice. Clin Exp Immunol. 1978 Sep;33(3):463–473. [PMC free article] [PubMed] [Google Scholar]
  8. Bolton W. K., Sturgill B. C. Bovine serum albumin chronic serum sickness nephropathy in rats. Br J Exp Pathol. 1978 Apr;59(2):167–177. [PMC free article] [PubMed] [Google Scholar]
  9. Couser W. G., Stilmant M. M. Mesangial lesions and focal glomerular sclerosis in the aging rat. Lab Invest. 1975 Nov;33(5):491–501. [PubMed] [Google Scholar]
  10. Elema J. D., Arends A. Focal and segmental glomerular hyalinosis and sclerosis in the rat. Lab Invest. 1975 Nov;33(5):554–561. [PubMed] [Google Scholar]
  11. GUTTMAN P. H., KOHN H. I. Progressive intercapillary glomerulosclerosis in the mouse, rat, and Chinese hamster, associated with aging and x-ray exposure. Am J Pathol. 1960 Sep;37:293–307. [PMC free article] [PubMed] [Google Scholar]
  12. Gershwin M. E., Steinberg A. D. Suppression of autoimmune hemolytic anemia in New Zealand (NZB) mice by syngeneic young thymocytes. Clin Immunol Immunopathol. 1975 May;4(1):38–45. doi: 10.1016/0090-1229(75)90037-9. [DOI] [PubMed] [Google Scholar]
  13. Gray J. E., Weaver R. N., Purmalis A. Ultrastructural observations of chronic progressive nephrosis in the Sprague-Dawley rat. Vet Pathol. 1974;11(2):153–164. doi: 10.1177/030098587401100207. [DOI] [PubMed] [Google Scholar]
  14. Guttman P. H., Bailey D. W. Potentiating effect of neonatal thymectomy on x-ray-induced intercapillary glomerulosclerosis. Nature. 1965 Jul 31;207(996):539–540. doi: 10.1038/207539a0. [DOI] [PubMed] [Google Scholar]
  15. Hirokawa K. Characterization of age-associated kidney disease in Wistar rats. Mech Ageing Dev. 1975 May-Aug;4(3-4):301–316. doi: 10.1016/0047-6374(75)90031-7. [DOI] [PubMed] [Google Scholar]
  16. Hoyer J. R., Spiro R. G. Studies on the rat glomerular basement membrane: age-related changes in composition. Arch Biochem Biophys. 1978 Jan 30;185(2):496–503. doi: 10.1016/0003-9861(78)90194-7. [DOI] [PubMed] [Google Scholar]
  17. KENNEDY G. C. Effects of old age and over-nutrition on the kidney. Br Med Bull. 1957 Jan;13(1):67–70. doi: 10.1093/oxfordjournals.bmb.a069575. [DOI] [PubMed] [Google Scholar]
  18. Kalant N., Satomi S., White R., Tel E. Changes in renal glomerular basement membrane with age and nephritis. Can J Biochem. 1977 Dec;55(12):1197–1206. doi: 10.1139/o77-179. [DOI] [PubMed] [Google Scholar]
  19. Kraus B., Cain H. Uber eine spontane Nephropathie bei Wistarratten. Die licht- und elektronenmikroskopischen Glomerulumveränderungen. Virchows Arch A Pathol Anat Histol. 1974;363(4):343–358. doi: 10.1007/BF00447845. [DOI] [PubMed] [Google Scholar]
  20. Kreisberg J. I., Karnovsky M. J. Focal glomerular sclerosis in the fawn-hooded rat. Am J Pathol. 1978 Sep;92(3):637–652. [PMC free article] [PubMed] [Google Scholar]
  21. Lalich J. J., Allen J. R. Protein overload nephropathy in rats with unilateral nephrectomy. II. Ultrastructural study. Arch Pathol. 1971 Apr;91(4):372–382. [PubMed] [Google Scholar]
  22. Latta H. The glomerular cappillary wall. J Ultrastruct Res. 1970 Sep;32(5):526–544. doi: 10.1016/s0022-5320(70)80026-0. [DOI] [PubMed] [Google Scholar]
  23. MUELLER C. B., MASON A. D., Jr, STOUT D. G. Anatomy of the glomerulus. Am J Med. 1955 Feb;18(2):267–276. doi: 10.1016/0002-9343(55)90242-4. [DOI] [PubMed] [Google Scholar]
  24. McNelly N. A., Dittmer J. E. Glomerular basement membrane width and proteinuria in the aging hamster kidney. Exp Gerontol. 1976;11(1-2):49–55. doi: 10.1016/0531-5565(76)90011-5. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Peter C. P. Possible immune origin of age-related pathological changes in long-lived mice. J Gerontol. 1973 Jul;28(3):265–275. doi: 10.1093/geronj/28.3.265. [DOI] [PubMed] [Google Scholar]
  27. Pollard M., Kajima M. Lesions in aged germfree Wistar rats. Am J Pathol. 1970 Oct;61(1):25–36. [PMC free article] [PubMed] [Google Scholar]
  28. Romen W. Licht- und elektronenmikroskopische Untersuchungen zur Pathogenese der altersbedingten Glomerulosklerose. Verh Dtsch Ges Pathol. 1975;59:370–375. [PubMed] [Google Scholar]
  29. Rosenquist T. H., Bernick S. Histochemistry of renal basal laminae. Adolescent compared with senescent rats. J Gerontol. 1971 Apr;26(2):176–185. doi: 10.1093/geronj/26.2.176. [DOI] [PubMed] [Google Scholar]
  30. SELLERS A. L., GOODMAN H. C., MARMORSTON J., SMITH M. Sex difference in proteinuria in the rat. Am J Physiol. 1950 Dec;163(3):662–667. doi: 10.1152/ajplegacy.1950.163.3.662. [DOI] [PubMed] [Google Scholar]
  31. Seiler M. W., Venkatachalam M. A., Cotran R. S. Glomerular epithelium: structural alterations induced by polycations. Science. 1975 Aug 1;189(4200):390–393. doi: 10.1126/science.1145209. [DOI] [PubMed] [Google Scholar]
  32. Teague P. O., Friou G. J. Antinuclear antibodies in mice. II. Transmission with spleen cells; inhibition or prevention with thymus or spleen cells. Immunology. 1969 Nov;17(5):665–675. [PMC free article] [PubMed] [Google Scholar]
  33. Teague P. O., Yunis E. J., Rodey G., Fish A. J., Stutman O., Good R. A. Autoimmune phenomena and renal disease in mice. Role of thymectomy, aging, and involution of immunologic capacity. Lab Invest. 1970 Feb;22(2):121–130. [PubMed] [Google Scholar]
  34. Wachtel L. W., Cole L. J., Rosen V. J. X-ray-induced glomerulosclerosis in rats: modification of lesion by food restriction, uninephrectomy, and age. J Gerontol. 1966 Jul;21(3):442–448. doi: 10.1093/geronj/21.3.442. [DOI] [PubMed] [Google Scholar]
  35. YAMADA E. The fine structure of the renal glomerulus of the mouse. J Biophys Biochem Cytol. 1955 Nov 25;1(6):551–566. doi: 10.1083/jcb.1.6.551. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES