Abstract
Focal and segmental glomerulosclerosis (FSGS) represents a final pathologic pattern of a number of human renal disorders. Among laboratory models, repeated intraperitoneal injections of the aminonucleoside of puromycin (PA) produces a histologic pattern not unlike the human process. A single intravenous dose of this drug usually results in glomerular morphologic changes in rats resembling those in human nephrotic syndrome with minimal changes. This report describes acute and chronic glomerular injury that begins as early as 8 days after a single central administration of PA and progresses to FSGS within an 18-week period. It seems likely that minimal change disease and FSGS are two pathologic processes in the same continuum of disease. In this model, the severity and persistence of the glomerular lesion may represent irreversible glomerular epithelial cell (GEC) injury secondary to the toxic effects of PA.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abramowsky C. R., Aikawa M., Swinehart G. L., Snajdar R. M. Spontaneous nephrotic syndrome in a genetic rat model. Am J Pathol. 1984 Dec;117(3):400–408. [PMC free article] [PubMed] [Google Scholar]
- Baldwin D. S. Chronic glomerulonephritis: nonimmunologic mechanisms of progressive glomerular damage. Kidney Int. 1982 Jan;21(1):109–120. doi: 10.1038/ki.1982.17. [DOI] [PubMed] [Google Scholar]
- Bohrer M. P., Baylis C., Robertson C. R., Brenner B. M., Troy J. L., Willis W. T. Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules. J Clin Invest. 1977 Jul;60(1):152–161. doi: 10.1172/JCI108751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Castellot J. J., Jr, Hoover R. L., Harper P. A., Karnovsky M. J. Heparin and glomerular epithelial cell-secreted heparin-like species inhibit mesangial-cell proliferation. Am J Pathol. 1985 Sep;120(3):427–435. [PMC free article] [PubMed] [Google Scholar]
- Caulfield J. P., Farquhar M. G. Loss of anionic sites from the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest. 1978 Nov;39(5):505–512. [PubMed] [Google Scholar]
- Coffey A. K., Karnovsky M. J. Heparin inhibits mesangial cell proliferation in habu-venom-induced glomerular injury. Am J Pathol. 1985 Aug;120(2):248–255. [PMC free article] [PubMed] [Google Scholar]
- Cotran R. S., Rennke H. G. Anionic sites and the mechanisms of proteinuria. N Engl J Med. 1983 Oct 27;309(17):1050–1052. doi: 10.1056/NEJM198310273091709. [DOI] [PubMed] [Google Scholar]
- 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]
- Derr R. F., Alexander C. S., Nagasawa H. T. Metabolism of puromycin aminonucleoside in the normal, "pre-nephrotic," and nephrotic rat. Proc Soc Exp Biol Med. 1967 May;125(1):248–252. doi: 10.3181/00379727-125-32061. [DOI] [PubMed] [Google Scholar]
- Diamond J. R., Bonventre J. V., Karnovsky M. J. A role for oxygen free radicals in aminonucleoside nephrosis. Kidney Int. 1986 Feb;29(2):478–483. doi: 10.1038/ki.1986.24. [DOI] [PubMed] [Google Scholar]
- 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]
- Fajardo L. F., Eltringham J. R., Stewart J. R., Klauber M. R. Adriamycin nephrotoxicity. Lab Invest. 1980 Sep;43(3):242–253. [PubMed] [Google Scholar]
- Fishman J. A., Karnovsky M. J. Effects of the aminonucleoside of puromycin on glomerular epithelial cells in vitro. Am J Pathol. 1985 Mar;118(3):398–407. [PMC free article] [PubMed] [Google Scholar]
- Glasser R. J., Velosa J. A., Michael A. F. Experimental model of focal sclerosis. I. Relationship to protein excretion in aminonucleoside nephrosis. Lab Invest. 1977 May;36(5):519–526. [PubMed] [Google Scholar]
- Grond J., Koudstaal J., Elema J. D. Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis. Kidney Int. 1985 Feb;27(2):405–410. doi: 10.1038/ki.1985.24. [DOI] [PubMed] [Google Scholar]
- Grond J., Weening J. J., Elema J. D. Glomerular sclerosis in nephrotic rats. Comparison of the long-term effects of adriamycin and aminonucleoside. Lab Invest. 1984 Sep;51(3):277–285. [PubMed] [Google Scholar]
- Hostetter T. H., Olson J. L., Rennke H. G., Venkatachalam M. A., Brenner B. M. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981 Jul;241(1):F85–F93. doi: 10.1152/ajprenal.1981.241.1.F85. [DOI] [PubMed] [Google Scholar]
- Hostetter T. H., Rennke H. G., Brenner B. M. Compensatory renal hemodynamic injury: a final common pathway of residual nephron destruction. Am J Kidney Dis. 1982 Mar;1(5):310–314. doi: 10.1016/s0272-6386(82)80032-2. [DOI] [PubMed] [Google Scholar]
- Ichikawa I., Rennke H. G., Hoyer J. R., Badr K. F., Schor N., Troy J. L., Lechene C. P., Brenner B. M. Role for intrarenal mechanisms in the impaired salt excretion of experimental nephrotic syndrome. J Clin Invest. 1983 Jan;71(1):91–103. doi: 10.1172/JCI110756. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanwar Y. S., Jakubowski M. L. Unaltered anionic sites of glomerular basement membrane in aminonucleoside nephrosis. Kidney Int. 1984 Apr;25(4):613–618. doi: 10.1038/ki.1984.65. [DOI] [PubMed] [Google Scholar]
- Kerjaschki D., Vernillo A. T., Farquhar M. G. Reduced sialylation of podocalyxin--the major sialoprotein of the rat kidney glomerulus--in aminonucleoside nephrosis. Am J Pathol. 1985 Mar;118(3):343–349. [PMC free article] [PubMed] [Google Scholar]
- 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]
- LANNIGAN R. The production of chronic renal disease in rats by a single intravenous injection of aminonucleoside of puromycin and the effect of low dosage continuous hydrocortisone. Br J Exp Pathol. 1963 Jun;44:326–333. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Mynderse L. A., Hassell J. R., Kleinman H. K., Martin G. R., Martinez-Hernandez A. Loss of heparan sulfate proteoglycan from glomerular basement membrane of nephrotic rats. Lab Invest. 1983 Mar;48(3):292–302. [PubMed] [Google Scholar]
- Olson J. L. Role of heparin as a protective agent following reduction of renal mass. Kidney Int. 1984 Feb;25(2):376–382. doi: 10.1038/ki.1984.27. [DOI] [PubMed] [Google Scholar]
- Olson J. L., de Urdaneta A. G., Heptinstall R. H. Glomerular hyalinosis and its relation to hyperfiltration. Lab Invest. 1985 Apr;52(4):387–398. [PubMed] [Google Scholar]
- 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]
- Purkerson M. L., Joist J. H., Greenberg J. M., Kay D., Hoffsten P. E., Klahr S. Inhibition by anticoagulant drugs of the progressive hypertension and uremia associated with renal infarction in rats. Thromb Res. 1982 May 15;26(4):227–240. doi: 10.1016/0049-3848(82)90287-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Seiler M. W., Hoyer J. R., Krueger T. E. Altered localization of protamine-heparin complexes in aminonucleoside nephrosis. Lab Invest. 1980 Jul;43(1):9–17. [PubMed] [Google Scholar]
- Shimamura T., Morrison A. B. A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am J Pathol. 1975 Apr;79(1):95–106. [PMC free article] [PubMed] [Google Scholar]
- Velosa J. A., Glasser R. J., Nevins T. E., Michael A. F. Experimental model of focal sclerosis. II. Correlation with immunopathologic changes, macromolecular kinetics, and polyanion loss. Lab Invest. 1977 May;36(5):527–534. [PubMed] [Google Scholar]