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. 1985 Sep;76(3):930–936. doi: 10.1172/JCI112092

Inhibitory role of dietary protein restriction on the development and expression of immune-mediated antitubular basement membrane-induced tubulointerstitial nephritis in rats.

D Agus, R Mann, D Cohn, L Michaud, C Kelly, M Clayman, E G Neilson
PMCID: PMC423956  PMID: 4044836

Abstract

The protective effect of dietary protein restriction on the development and expression of immune-mediated interstitial nephritis was evaluated in Brown Norway rats with anti-tubular basement membrane disease. In the first series of experiments, pair-fed rats received low protein (LP) (3% casein) or normal protein (NP) (27% casein), normocaloric diets. After 6 wk, each group was immunized with renal tubular antigen in adjuvant to produce anti-tubular basement membrane antibody (alpha TBM-Ab) and tubulointerstitial nephritis. The kidneys harvested from NP rats after four more weeks on the diet had histologically more severe interstitial disease than the LP rats (histologic severity; NP = 3.1 +/- 0.2 vs. LP = 1.1 +/- 0.3; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.34 +/- 0.02 vs. LP = 0.82 +/- 0.03). Titers of alpha TBM-Ab were similar in both groups, while the T cell-mediated immune response, as measured by delayed-type hypersensitivity (DTH), was nonspecifically impaired in LP rats when compared with the NP group. Admixture cotransfers of LP plus NP cells failed to demonstrate active suppression as an explanation for the depressed DTH in LP rats. The therapeutic role of dietary protein restriction was also examined in rats with established alpha TBM disease. In these experiments, rats were first immunized and fed NP diets for 4 wk (histologic severity = 3.0 +/- 0.2; creatinine = 1.78 +/- 0.02), and then were divided into two groups and followed for six more weeks on either LP or NP diets. LP rats, under these conditions, developed less disease than those fed NP diet (histologic severity; NP = 3.2 +/- 0.3 vs. LP = 1.4 +/- 0.2; P less than 0.001), and serum creatinine values were concordantly different (NP = 1.92 +/- 0.05 vs. LP = 0.97 +/- 0.02). Again, the titers of alpha TBM-Ab in both LP and NP groups were similar. These data collectively suggest that LP diet has a protective effect both on the development and extent of tubulointerstitial nephritis that is perhaps, in part, related to the selective abrogation of effector T cell immunity.

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Selected References

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  1. Andres G. A., McCluskey R. T. Tubular and interstitial renal disease due to immunologic mechanisms. Kidney Int. 1975 Apr;7(4):271–289. doi: 10.1038/ki.1975.38. [DOI] [PubMed] [Google Scholar]
  2. Bohle A., Christ H., Grund K. E., Mackensen S. The role of the interstitium of the renal cortex in renal disease. Contrib Nephrol. 1979;16:109–114. doi: 10.1159/000402883. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Clark C. C. The distribution and initial characterization of oligosaccharide units on the COOH-terminal propeptide extensions of the pro-alpha 1 and pro-alpha 2 chains of type I procollagen. J Biol Chem. 1979 Nov 10;254(21):10798–10802. [PubMed] [Google Scholar]
  5. Cooper W. C., Good R. A., Mariani T. Effects of protein insufficiency on immune responsiveness. Am J Clin Nutr. 1974 Jun;27(6):647–664. doi: 10.1093/ajcn/27.6.647. [DOI] [PubMed] [Google Scholar]
  6. Fernandes G., Friend P., Yunis E. J., Good R. A. Influence of dietary restriction on immunologic function and renal disease in (NZB x NZW) F1 mice. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1500–1504. doi: 10.1073/pnas.75.3.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fernandes G., Yunis E. J., Good R. A. Influence of diet on survival of mice. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1279–1283. doi: 10.1073/pnas.73.4.1279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernandes G., Yunis E. J., Good R. A. Influence of protein restriction on immune functions in NZB mice. J Immunol. 1976 Mar;116(3):782–790. [PubMed] [Google Scholar]
  9. Fernandes G., Yunis E. J., Miranda M., Smith J., Good R. A. Nutritional inhibition of genetically determined renal disease and autoimmunity with prolongation of life in kdkd mice. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2888–2892. doi: 10.1073/pnas.75.6.2888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Good R. A., Fernandes G., Yunis E. J., Cooper W. C., Jose D. C., Kramer T. R., Hansen M. A. Nutritional deficiency, immunologic function, and disease. Am J Pathol. 1976 Sep;84(3):599–614. [PMC free article] [PubMed] [Google Scholar]
  11. Good R. A., West A., Fernandes G. Nutritional modulation of immune responses. Fed Proc. 1980 Nov;39(13):3098–3104. [PubMed] [Google Scholar]
  12. Husdan H., Rapoport A. Estimation of creatinine by the Jaffe reaction. A comparison of three methods. Clin Chem. 1968 Mar;14(3):222–238. [PubMed] [Google Scholar]
  13. Ibels L. S., Alfrey A. C., Haut L., Huffer W. E. Preservation of function in experimental renal disease by dietary restriction of phosphate. N Engl J Med. 1978 Jan 19;298(3):122–126. doi: 10.1056/NEJM197801192980302. [DOI] [PubMed] [Google Scholar]
  14. Katz A. I., Epstein F. H. Physiologic role of sodium-potassium-activated adenosine triphosphatase in the transport of cations across biologic membranes. N Engl J Med. 1968 Feb 1;278(5):253–261. doi: 10.1056/NEJM196802012780506. [DOI] [PubMed] [Google Scholar]
  15. Kenny M. A., Roderuck C. E., Arnrich L., Piedad F. Effect of protein deficiency on the spleen and antibody formation in rats. J Nutr. 1968 Jun;95(2):173–178. doi: 10.1093/jn/95.2.173. [DOI] [PubMed] [Google Scholar]
  16. Klahr S., Buerkert J., Purkerson M. L. Role of dietary factors in the progression of chronic renal disease. Kidney Int. 1983 Nov;24(5):579–587. doi: 10.1038/ki.1983.197. [DOI] [PubMed] [Google Scholar]
  17. Mathur M., Ramalingaswami V., Deo M. G. Influence of protein deficiency on 19S antibody-forming cells in rats and mice. J Nutr. 1972 Jul;102(7):841–846. doi: 10.1093/jn/102.7.841. [DOI] [PubMed] [Google Scholar]
  18. Matsumoto K., McCafferty E., Neilson E. G., Gasser D. L. Mapping of the genes for tubular basement membrane antigen and a submaxillary gland protease in the rat. Immunogenetics. 1984;20(2):117–123. doi: 10.1007/BF00364483. [DOI] [PubMed] [Google Scholar]
  19. Murray T., Goldberg M. Chronic interstitial nephritis: etiologic factors. Ann Intern Med. 1975 Apr;82(4):453–459. doi: 10.7326/0003-4819-82-4-453. [DOI] [PubMed] [Google Scholar]
  20. Neilson E. G., Gasser D. L., McCafferty E., Zakheim B., Phillips S. M. Polymorphism of genes involved in anti-tubular basement membrane disease in rats. Immunogenetics. 1983;17(1):55–65. doi: 10.1007/BF00364289. [DOI] [PubMed] [Google Scholar]
  21. Neilson E. G., McCafferty E., Phillips S. M., Clayman M. D., Kelly C. J. Antiidiotypic immunity in interstitial nephritis. II. Rats developing anti-tubular basement membrane disease fail to make an antiidiotypic regulatory response: the modulatory role of an RT7.1+, OX8- suppressor T cell mechanism. J Exp Med. 1984 Apr 1;159(4):1009–1026. doi: 10.1084/jem.159.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Neilson E. G., Phillips M. Suppression of interstitial nephritis by auto-anti-idiotypic immunity. J Exp Med. 1982 Jan 1;155(1):179–189. doi: 10.1084/jem.155.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Neilson E. G., Phillips S. M. Cell-mediated immunity in interstitial nephritis. I. T lymphocyte systems in nephritic guinea pigs: the natural history and diversity of the immune response. J Immunol. 1979 Nov;123(5):2373–2380. [PubMed] [Google Scholar]
  24. Neilson E. G., Phillips S. M. Murine interstitial nephritis. I. Analysis of disease susceptibility and its relationship of pleiomorphic gene products defining both immune-response genes and a restrictive requirement for cytotoxic T cells at H-2K. J Exp Med. 1982 Apr 1;155(4):1075–1085. doi: 10.1084/jem.155.4.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Neilson E. G., Zakheim B. T cell regulation, anti-idiotypic immunity, and the nephritogenic immune response. Kidney Int. 1983 Sep;24(3):289–302. doi: 10.1038/ki.1983.158. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Report of the American Institute of Nurtition ad hoc Committee on Standards for Nutritional Studies. J Nutr. 1977 Jul;107(7):1340–1348. doi: 10.1093/jn/107.7.1340. [DOI] [PubMed] [Google Scholar]
  28. Rudofsky U. H. Studies on the pathogenesis of experimental autoimmune renal tubulointerstitial disease in guinea-pigs. III. The role of adjuvants in the induction of disease. Clin Exp Immunol. 1976 Sep;25(3):455–461. [PMC free article] [PubMed] [Google Scholar]
  29. Scrimshaw N. S. Shattuck lecture--strengths and weaknesses of the committee approach. An analysis of past and present recommended dietary allowances for protein in health and disease (second of two parts). N Engl J Med. 1976 Jan 22;294(4):198–203. doi: 10.1056/NEJM197601222940405. [DOI] [PubMed] [Google Scholar]

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