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. 1990 Apr;85(4):1119–1126. doi: 10.1172/JCI114543

Glomerular hypertrophy aggravates epithelial cell injury in nephrotic rats.

P L Miller 1, J W Scholey 1, H G Rennke 1, T W Meyer 1
PMCID: PMC296542  PMID: 2318969

Abstract

Glomerular function and structure were assessed after reduction of nephron number and restriction of protein intake in rats with adriamycin nephrosis. Rats received an injection of adriamycin and were divided into three groups with similar values for albuminuria after 4 wk. Group 1 rats then served as controls, group 2 rats were subjected to four-fifths renal ablation, and group 3 rats were placed on a low protein diet (8% protein) while group 1 and group 2 rats remained on a standard diet (24% protein). Micropuncture and morphometric studies were performed 10 d later. Estimated single-nephron albuminuria (SNalb) was increased by renal ablation in group 2 and decreased by protein restriction in group 3 (group 1, 20 +/- 2 micrograms/d; group 2, 68 +/- 7 micrograms/d; group 3, 12 +/- 1 microgram/d, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb was associated with increased glomerular volume in group 2 and reduced SNalb was associated with reduced glomerular volume in group 3. (group 1, 1.44 +/- 0.04 x 10(6) microns 3; group 2, 1.66 +/- 0.08 x 10(6) microns 3; group 3, 1.26 +/- 0.03 x 10(6) microns 3, P less than 0.05 groups 2 and 3 vs. 1). Increased SNalb in group 2 was not associated with an increase in glomerular transcapillary hydraulic pressure. The area of epithelial cell detachment from the peripheral capillary wall was markedly increased in group 2 but not perceptibly altered in group 3 (group 1, 16 +/- 5 x 10(2) microns 2; group 2, 65 +/- 17 x 10(2) microns 2; group 3, 18 +/- 5 x 10(2) microns 2; P less than 0.05 group 2 vs. 1). These studies show that glomerular hypertrophy is associated with increased epithelial cell detachment from the peripheral capillary wall and with increased remnant nephron albuminuria after reduction of nephron number in rats with established nephrosis.

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Selected References

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

  1. Anderson S., Meyer T. W., Rennke H. G., Brenner B. M. Control of glomerular hypertension limits glomerular injury in rats with reduced renal mass. J Clin Invest. 1985 Aug;76(2):612–619. doi: 10.1172/JCI112013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson S., Rennke H. G., Brenner B. M. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986 Jun;77(6):1993–2000. doi: 10.1172/JCI112528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arakawa M., Tokunaga J. A scanning electron microscope study of the glomerulus. Further consideration of the mechanism of the fusion of podocyte terminal processes in nephrotic rats. Lab Invest. 1972 Oct;27(4):366–371. [PubMed] [Google Scholar]
  4. Baldwin D. S., Neugarten J. Role of hypertension in the evolution of renal diseases. Contrib Nephrol. 1987;54:63–76. doi: 10.1159/000413214. [DOI] [PubMed] [Google Scholar]
  5. Beukers J. J., Hoedemaeker P. J., Weening J. J. A comparison of the effects of converting-enzyme inhibition and protein restriction in experimental nephrosis. Lab Invest. 1988 Nov;59(5):631–640. [PubMed] [Google Scholar]
  6. Brenner B. M., Meyer T. W., Hostetter T. H. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982 Sep 9;307(11):652–659. doi: 10.1056/NEJM198209093071104. [DOI] [PubMed] [Google Scholar]
  7. Brenner B. M. Nephron adaptation to renal injury or ablation. Am J Physiol. 1985 Sep;249(3 Pt 2):F324–F337. doi: 10.1152/ajprenal.1985.249.3.F324. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Fries J. W., Rumpelt H. J., Thoenes W. Alterations of glomerular podocytic processes in immunologically mediated glomerular disorders. Kidney Int. 1987 Nov;32(5):742–748. doi: 10.1038/ki.1987.269. [DOI] [PubMed] [Google Scholar]
  10. Fries J. W., Sandstrom D. J., Meyer T. W., Rennke H. G. Glomerular hypertrophy and epithelial cell injury modulate progressive glomerulosclerosis in the rat. Lab Invest. 1989 Feb;60(2):205–218. [PubMed] [Google Scholar]
  11. Grishman E., Churg J. Focal glomerular sclerosis in nephrotic patients: an electron microscopic study of glomerular podocytes. Kidney Int. 1975 Feb;7(2):111–122. doi: 10.1038/ki.1975.16. [DOI] [PubMed] [Google Scholar]
  12. Kanwar Y. S., Rosenzweig L. J. Altered glomerular permeability as a result of focal detachment of the visceral epithelium. Kidney Int. 1982 Apr;21(4):565–574. doi: 10.1038/ki.1982.63. [DOI] [PubMed] [Google Scholar]
  13. Kaysen G. A., Gambertoglio J., Felts J., Hutchison F. N. Albumin synthesis, albuminuria and hyperlipemia in nephrotic patients. Kidney Int. 1987 Jun;31(6):1368–1376. doi: 10.1038/ki.1987.151. [DOI] [PubMed] [Google Scholar]
  14. Markwell M. A., Haas S. M., Bieber L. L., Tolbert N. E. A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem. 1978 Jun 15;87(1):206–210. doi: 10.1016/0003-2697(78)90586-9. [DOI] [PubMed] [Google Scholar]
  15. Mauer S. M., Steffes M. W., Ellis E. N., Sutherland D. E., Brown D. M., Goetz F. C. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984 Oct;74(4):1143–1155. doi: 10.1172/JCI111523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Messina A., Davies D. J., Dillane P. C., Ryan G. B. Glomerular epithelial abnormalities associated with the onset of proteinuria in aminonucleoside nephrosis. Am J Pathol. 1987 Feb;126(2):220–229. [PMC free article] [PubMed] [Google Scholar]
  17. Meyer T. W., Rennke H. G. Increased single-nephron protein excretion after renal ablation in nephrotic rats. Am J Physiol. 1988 Dec;255(6 Pt 2):F1243–F1248. doi: 10.1152/ajprenal.1988.255.6.F1243. [DOI] [PubMed] [Google Scholar]
  18. Miller P. L., Meyer T. W. Plasma protein concentration and colloid osmotic pressure in nephrotic rats. Kidney Int. 1988 Aug;34(2):220–223. doi: 10.1038/ki.1988.167. [DOI] [PubMed] [Google Scholar]
  19. Nath K. A., Kren S. M., Hostetter T. H. Dietary protein restriction in established renal injury in the rat. Selective role of glomerular capillary pressure in progressive glomerular dysfunction. J Clin Invest. 1986 Nov;78(5):1199–1205. doi: 10.1172/JCI112703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Neugarten J., Feiner H. D., Schacht R. G., Baldwin D. S. Amelioration of experimental glomerulonephritis by dietary protein restriction. Kidney Int. 1983 Nov;24(5):595–601. doi: 10.1038/ki.1983.199. [DOI] [PubMed] [Google Scholar]
  21. Olson J. L., Heptinstall R. H. Nonimmunologic mechanisms of glomerular injury. Lab Invest. 1988 Nov;59(5):564–578. [PubMed] [Google Scholar]
  22. Olson J. L., Hostetter T. H., Rennke H. G., Brenner B. M., Venkatachalam M. A. Altered glomerular permselectivity and progressive sclerosis following extreme ablation of renal mass. Kidney Int. 1982 Aug;22(2):112–126. doi: 10.1038/ki.1982.143. [DOI] [PubMed] [Google Scholar]
  23. Osterby R., Gundersen H. J. Fast accumulation of basement membrane material and the rate of morphological changes in acute experimental diabetic glomerular hypertrophy. Diabetologia. 1980 Jun;18(6):493–500. doi: 10.1007/BF00261706. [DOI] [PubMed] [Google Scholar]
  24. Purkerson M. L., Hoffsten P. E., Klahr S. Pathogenesis of the glomerulopathy associated with renal infarction in rats. Kidney Int. 1976 May;9(5):407–417. doi: 10.1038/ki.1976.50. [DOI] [PubMed] [Google Scholar]
  25. Rosenberg M. E., Swanson J. E., Thomas B. L., Hostetter T. H. Glomerular and hormonal responses to dietary protein intake in human renal disease. Am J Physiol. 1987 Dec;253(6 Pt 2):F1083–F1090. doi: 10.1152/ajprenal.1987.253.6.F1083. [DOI] [PubMed] [Google Scholar]
  26. Ryan G. B., Karnovsky M. J. An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Kidney Int. 1975 Oct;8(4):219–232. doi: 10.1038/ki.1975.105. [DOI] [PubMed] [Google Scholar]
  27. Scholey J. W., Miller P. L., Rennke H. G., Meyer T. W. Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy. Kidney Int. 1989 Nov;36(5):816–822. doi: 10.1038/ki.1989.267. [DOI] [PubMed] [Google Scholar]
  28. Weening J. J., Rennke H. G. Glomerular permeability and polyanion in adriamycin nephrosis in the rat. Kidney Int. 1983 Aug;24(2):152–159. doi: 10.1038/ki.1983.139. [DOI] [PubMed] [Google Scholar]
  29. Yoshida Y., Fogo A., Ichikawa I. Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int. 1989 Feb;35(2):654–660. doi: 10.1038/ki.1989.35. [DOI] [PubMed] [Google Scholar]

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