Laboratory Investigation

Kidney International (1985) 27, 739–750; doi:10.1038/ki.1985.74

Effect of protein intake on renal function and structure in partially nephrectomized rats

Charles H Kenner1,1, Andrew P Evan1, Phillip Blomgren1, George R Aronoff1 and Friedrich C Luft1

1Department of Medicine, Section of Nephrology, and the Department of Anatomy, Indiana University School of Medicine, Indianapolis, Indiana, USA

Correspondence: Dr F C Luft, Nephrology Section, Department of Medicine, Indiana University Medical Center, Fesler Hall 108, 1120 South Drive, Indianapolis, Indiana 46223, USA

1Dr. Charles H. Kenner expired in October of 1984.

Received 10 April 1984; Revised 12 October 1984.

Top

Abstract

Effects of protein intake on renal function and structure in partially nephrectomized rats. To examine the effect of high protein intake on renal function and structure in rats with 5/6 nephrectomy chronic renal failure, we pairfed rats with chronic renal failure and sham-operated control rats diets of 14 or 37% protein content for up to 6 months. High protein intake accelerated mortality in rats with chronic renal failure and resulted in a more rapid rate of decrease in renal function as established by plotting the reciprocal of plasma creatinine versus time. High protein intake also increased urine protein excretion in experimental and control rats. High protein intake was associated with increased tubular dilatation and interstitial inflammation, both of which were striking features in rats with chronic renal failure. Glomerular sclerosis was prominent in rats with chronic renal failure. These rats had smaller glomerular tuft dimensions than control rats irrespective of their protein intake. We conclude that high protein intake accelerates the course of chronic renal failure in rats. The pathologic process involves glomerular sclerosis; however, interstitial inflammation and renal tubular changes leading to cyst formation also appear to influence the process adversely.

Effet de l'apport protéique sur la fonction et la structure rénales de rats partiellement néphrectomisés. Afin d'examiner l'effet d'un apport protéique élevé sur la fonction et la structure rénales de rats en insuffisance rénale chronique par néphrectomie des 5/6e, nous avons nourri de façon appariée des rats ayant subi un simulacre d'intervention avec des régimes contenant 14 ou 37% de protéines pendant 6 mois. Le fort apport protéique a accéléré la mortalité des rats en insuffisance rénale chronique et a entrainé une plus rapide vitesse de décroissance de la fonction rénale, établie en représentant l'inverse de la créatininémie en fonction du temps. Le fort apport protéique a également augmenté l'excrétion urinaire de protéines chez les rats contrôles et expérimentaux. Le fort apport protéique était associé à une augmentation de la dilatation tubulaire, et de l'inflammation interstitielle, chacune étant une caractéristique marquante des rats en insuffisance rénale chronique. La sclérose glomérulaire était notable chez les rats en insuffisance rénale chronique. Ces rats avaient des touffes glomérulaires de plus petites dimensions que les rats contrôles quel que soit leur apport protéique. Nous concluons qu'un apport protéique élevé accélère l'évolution de l'insuffisance rénale chronique chez les rats. Le processus pathologique met enjeu une sclérose glomérulaire; cependant, l'inflammation interstitielle et les changements tubulaire s rénaux aboutissant à la formation des kystes semblent également influencer le processus de façon défavorable.

Top

References

  1. Klahr S, Buerkert J, Purkerson ML: Role of dietary factors in the progression of chronic renal disease. Kidney Int 24:579–587, 1983 | PubMed | ISI | ChemPort |
  2. Brenner BM, Meyer TW, Hostetter TH: 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 307:652–659, 1982 | PubMed | ISI | ChemPort |
  3. Meyer WM, Anderson S, Brenner BM: Dietary protein intake and progressive glomerular sclerosis: The role of capillary hypertension and hyperperfusion in the progression of renal disease. Ann Int Med 98 (Part 2):832–838, 1983
  4. Kleinknecht C, Salusky I, Broyer M, Gubler M: Effect of various protein diets on growth, renal function, and survival of uremic rats. Kidney Int 15:534–541, 1979 | PubMed | ISI | ChemPort |
  5. Diaz M, Kleinknecht C, Broyer M: Growth in experimental renal failure: Role of calorie and amino acid intake. Kidney Int 8:349–354, 1975
  6. Kaufman JM, Siegel NJ, Hayslett JP: Functional and hemodynamic adaptation to progressive renal ablation. Circ Res 36:286–293, 1975 | PubMed |
  7. Salusky I, Kleinknecht C, Broyer M, Gubler M: Prolonged survival and stunting, with protein-deficient diets in experimental uremia. Reversal of these effects by addition of essential amino acids. J Lab Clin Med 97:21–30, 1981
  8. Shimamura T, Morrison AB: A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am J Pathol 79:95–101, 1975 | PubMed | ISI | ChemPort |
  9. Olson JL, Hostetter TH, Rennke HG, Brenner BM, Venkatachalam MA: Altered glomerular permeability and progressive sclerosis following ablation of renal mass. Kidney Int 22:112–126, 1982 | PubMed | ISI | ChemPort |
  10. Grond J, Schilthuis MS, Koudstaal J: Mesangial function and glomerular sclerosis in rats after unilateral nephrectomy. Kidney Int 22:338–334, 1982 | PubMed | ISI | ChemPort |
  11. Bradford MM: A rapid and sensitive method for quantitative determination of protein in urine. Clin Chem 23:811–812, 1977
  12. Hoeg JM, Willis LR, Weinberger MH: Estrogen effect on the development of hypertension in spontaneously hypertensive rats. Am J Physiol 233:369–373, 1977
  13. Gattone VH, Evan AP, Mong SA, Connors BA, Aronoff GR, Luft FC: The morphology of the renal microvasculature in glycerol and gentamicin induced acute renal failure. J Lab Clin Med 101:183–195, 1983
  14. Maschio G, Oldrizzi L, Tessitore N, D'Angelo A, Valvo E, Lupo A, Loschiavo C, Fabris A, Gammaro L, Rugiu C, Panzetta G: Effects of dietary protein and phosphate restriction on the progression of early renal failure. Kidney Int 22:371–376, 1982 | PubMed | ISI | ChemPort |
  15. Tucker SM, Mason RL, Beauchene RE: Influence of diet and feed restriction on kidney function of aging male rats. J Gerontol 31:264–270, 1976 | PubMed | ISI | ChemPort |
  16. Deen WM, Maddox DA, Robertson CR, Brenner BM: Dynamics of glomerular ultrafiltration in the rat. VII. Response to reduced renal mass. Am J Physiol 227:556–562, 1974 | PubMed |
  17. Andrews PM: Scanning electron microscopy of human and rhesus monkey kidneys. Lab Invest 32:610–620, 1975
  18. Purkerson ML, Hoffsten PE, Klahr S: Pathogenesis of the glomerulopathy associated with renal infarction in rats. Kidney Int 9:407–117, 1976 | PubMed | ISI | ChemPort |
  19. Mitch WE, Walser M, Buffington GA, Lemann J: A simple method for estimating progression of chronic renal failure. Lancet 2:1326–1328, 1976 | PubMed | ISI | ChemPort |
  20. Rutherford WE, Blondin J, Miller JP, Greenwalt AS, Vavra JD: Chronic progressive renal disease: Rate of change of serum creatinine. Kidney Int 11:62–70, 1977
  21. Namnum P, Insogna K, Baggish D, Hayslett JP: Evidence for bidirectional net movement of creatinine in the rat kidney. Am J Physiol 244:F119–F123 1983
  22. Zucchelli P, Cagnoli L, Casanova S, Donini U, Pasquali S: Focal glomerulosclerosis in patients with unilateral nephrectomy. Kidney Int 24:649–655, 1983
  23. Couser WG, Stilmant MM: Mesangial lesions and focal glomerular sclerosis in the aging rat. Lab Invest 33:491–501, 1975 | PubMed | ISI | ChemPort |
  24. Gardner KD, Evan AP: Cystic kidneys: An enigma evolves. Am J Kidney Dis 3:403–412, 1984
  25. Evan AP, Gardner KD, Bernstein J: Polypoid and papillary epithelial hyperplasia: A potential cause of ductal obstruction in adult polycystic disease. Kidney Int 16:743–750, 1979 | PubMed | ISI | ChemPort |
  26. Bricker NS, Klahr S, Rieselbach RE: The functional adaptation of the diseased kidney. I. Glomerular filtration rate. J Clin Invest 43:1915–1921, 1964 | PubMed | ISI | ChemPort |
  27. Bricker NS, Fine LG: The renal response to progressive nephron loss, in The Kidney (2nd ed), edited by Brenner BM, Rector FC, Jr, Philadelphia, W. B. Saunders, 1981, pp 1056–1096
  28. Malt RA: Compensatory growth of the kidney. N Engl J Med 280:1446–1458, 1969 | PubMed |
  29. Tomashefsky P, Tannenbaum M: Macromolecular metabolism in renal compensatory hypertrophy. I. Protein synthesis. Lab Invest 21:358–364, 1969
  30. Brezis M, Rosen S, Silva P, Spokes K, Epstein FH: Polyene toxicity in renal medulla: Injury mediated by transport activity. Science 244:66–68, 1984
  31. Kurnick NB, Lindsay PA: Nucleic acids in compensatory renal hypertrophy. Lab Invest 18:700–708, 1968
  32. Lefkowith JB, Okegawa T, DeSchryver-Kecskemeti K, Needleman P: Macrophage-dependent arachidonate metabolism in hydronephrosis. Kidney Int 26:10–17, 1984 | PubMed |

Extra navigation

.
ADVERTISEMENT