Laboratory Investigation

Kidney International (1988) 33, 561–570; doi:10.1038/ki.1988.34

Effect of diet, age and sex on the renal response to immune injury in the rat

Aida Yared, Hirofumi Miyazawa, Mabel L Purkerson, Saulo Klahr, David J Salant and Iekuni Ichikawa

Division of Nephrology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee; Renal Division, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; and Evans Memorial Department of Clinical Research and Department of Medicine, University Hospital, Boston University Medical Center, Boston, Massachusetts, USA

Correspondence: Dr A Yared, Division of Pediatric Nephrology, Vanderbilt University Medical Center, C-4204 M.C.N., Nashville, Tennessee 37232, USA.

Received 12 November 1986; Revised 11 August 1987.

Top

Abstract

Effect of diet, age and sex on the glomerular response to immune injury in the rat. We investigated the effect of three factors, namely dietary protein intake, age and sex, on the susceptibility of the renal glomerulus to the binding of antiglomerular basement membrane antibody (anti-GBM) in the early (heterologous) phase of anti-GBM nephritis, and the consequent reduction in glomerular filtration rate (GFR) as measured by inulin clearance (CIn). The effect of diet was examined in approximately 8 week-old female Munich-Wistar rats fed a 40% high (HP) or a 6% low (LP) protein diet, and that of sex and age in male and female rats, 6 week or 10 month old. Following an intravenous dose (3 to 20 microg/g body wt) of radiolabeled nephritogenic anti-GBM, assessment of glomerular function was followed by quantitation of anti-GBM binding (values corrected for GBM surface area) in isolated glomeruli. At a given plasma level of antibody, the degree of binding of anti-GBM was slightly but significantly higher in HP than LP-fed rats; the decrease in GFR was significantly more pronounced in HP than LP-fed animals. The amount of anti-GBM binding was significantly greater in adult than young animals; however, the consequent decrease in GFR was more pronounced in the young than adult animals. Sex dependency was not discernible in anti-GBM binding or reduction in GFR. In all of the above experimental groups, the degree of anti-GBM binding was closely correlated with the plasma level of anti-GBM, but not with effective renal plasma flow rate, measured by PAH clearance. Separate groups of rats were subjected to experimental manipulation of single nephron GFR, glomerular capillary hydraulic pressure and glomerular plasma flow rate, by partial aortic constriction and saralasin administration. This set of experiments, using a tracer amount of non-nephritogenic anti-GBM, revealed that glomerular anti-GBM binding is independent of any of the above parameters. The studies indicate that dietary protein intake and age, but not sex, are among the factors determining the susceptibility of the glomerulus to acute immune injury. Since the binding of anti-GBM is determined by the affinity property of the glomerulus per se, and not by the prevailing hemodynamic pattern, the observed dependence of susceptibility to functional impairment on age and protein intake appears to also reflect a property of the glomerulus, which is influenced by age and the degree of dietary protein intake.

Top

References

  1. Blantz RC, Wilson CB: Acute effects of antiglomerular basement membrane antibody on the process of glomerular filtration in the rat. J Clin Invest 58:899–911, 1976 | PubMed |
  2. Ichikawa I, Purkerson ML, Klahr S, Troy JL, Martinez-Maldonado M, Brenner BM: Mechanism of reduced glomerular filtration rate in chronic malnutrition. J Clin Invest 65:982–988, 1980
  3. Madaio MP, Salant DJ, Adler S, Darby C, Couser WG: Effect of antibody charge arid concentration on deposition of antibody to glomerular basement membrane. Kidney Int 26:397–403, 1984
  4. Krakower CA, Greenspoon SA: Localization of the nephrotoxin antigen within the isolated renal glomerulus. Arch Pathol 51:629–641, 1951 | ChemPort |
  5. Salant DJ, Belok S, Madaio MP, Couser WG: A new role for complement in experimental membranous nephropathy in rats. J Clin Invest 66:1339–1350, 1980 | PubMed | ISI | ChemPort |
  6. Outcherlony O: Handbook of Immunodiffusion and Immunoelectrophoresis. Ann Arbor, Humphrey Science Publishers, 1970
  7. McConahey PJ, Dixon FJ: A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol 29:185–189, 1966 | PubMed | ISI | ChemPort |
  8. Feintzeig ID, Dittmer JE, Cybulsky AV, Salant DJ: Antibody, antigen, and glomerular capillary wall charge interactions: Influence of antigen location on in situ immune complex formation. Kidney Int 29:649–657, 1986
  9. Ichikawa I, Maddox D, Brenner BM: Maturational development of glomerular ultrafiltration in the rat. Am J Physiol 236:F465–F471, 1979
  10. Ichikawa I, Maddox DA, Cogan MG, Brenner BM: Dynamics of glomerular ultrafiltration in euvolemic Munich-Wistar rats. Renal Physiol (Basel) 1:121–131, 1978
  11. Deen WM, Troy JL, Robertson CR, Brenner BM: Dynamics of glomerular ultrafiltration in the rat. IV. Determination of the ultrafiltration coefficient. J Clin Invest 52:1500–1508, 1973 | PubMed | ISI | ChemPort |
  12. Viets JW, Deen WM, Troy JL, Brenner BM: Determination of serum protein concentration in nanoliter blood samples using fluorescamine or o-phthalaldehyde. Anal Biochem 88:513–521, 1978 | Article | PubMed | ISI | ChemPort |
  13. Salant DJ, Darby C, Couser WG: Experimental membranous glomerulonephritis in rats. Quantitative studies of glomerular immune deposit formation in isolated glomeruli and whole animals. J Clin Invest 66:71–81, 1980 | PubMed | ISI | ChemPort |
  14. Smith HW, Finkelstein N, Aliminosa L, Crawford B, Graber M: The renal clearances of substituted hippuric acid derivatives and other aromatic amines in dog and man. J Clin Invest 24:388–404, 1945 | PubMed | ISI | ChemPort |
  15. Führ J, Kaczmarczyk J, Krüttgen CD: Eine einfache colorimetrische Methode zur Inulinbestimmung für Nieren-Clearance-Untersuchungen bei Stoffwechselgesunden und Diabetikern. Klin Wochenschr 33:729–730, 1955 | PubMed | ISI | ChemPort |
  16. Vurek GG, Pegram SE: Fluorometric method for the determination of nanogram quantities of inulin. Anal Biochem 16:409–419, 1966 | Article | ISI | ChemPort |
  17. Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein using the principle of protein-dye binding. Anal Biochem 72:248–254, 1976 | Article | PubMed | ISI | ChemPort |
  18. Ichikawa I, Brenner BM: Importance of efferent arteriolar vascular tone in regulation of proximal tubule fluid reabsorption and glomerulotubular balance in the rat. J Clin Invest 65:1192–1201, 1980
  19. Knutson DW, Chieu F, Bennett CM, Glassock RJ: Estimation of relative glomerular capillary surface area in normal and hypertrophic rat kidneys. Kidney Int 14:437–443, 1978
  20. Yoshioka T, Yared A, Kon V, Ichikawa I: Mechanism for impaired autoregulation of filtration in mammalian glomeruli during systemic circulatory derangement. Am J Physiol (submitted for publication)
  21. Blantz RC, Tucker BJ, Wilson CB: The acute effects of antiglomerular basement membrane antibody upon glomerular filtration in the rat. The influence of dose and complement depletion. J Clin Invest 61:910–921, 1978
  22. Druet P, Bariety J, Bellon B, Laliberte F: Nephrotoxic serum nephritis in the rat. Ultrastructural localization of nephrotoxic rabbit antibodies using peroxidase-labelled conjugates. Lab Invest 27:157–164, 1972
  23. Fresen KO, Vogt A: Ultrastructural localization of peroxidase-labelled nephrotoxic antibodies after intravenous application. Exp Pathol 8:276–282, 1973
  24. Trinh Trang Tan M-M, Bankir L, Diaz M, Grünfeld J-P: Antiglomerular basement membrane antibody and microsphere distribution in rat glomeruli. Renal Physiol (Base) 1:84–92, 1978
  25. Walvin JD, Rector FC Jr, Seldin DW: Measurement of intra-fenal plasma flow with antiglomerular basement-membrane antibody, Am J Physiol 221:1621–1628, 1971
  26. Abrahamson DR: Origin of the glomerular basement membrane visualized after in vivo labeling of laminin in newborn rat kidneys. J Cell Biol 100:1988–2000, 1985 | Article | PubMed | ISI | ChemPort |
  27. Blantz RC, Tucker BJ, Gushwa LC, Peterson ÖW, Wilson CB: Glomerular immune injury in the rat: The influence of angiotensin II and alpha-adrenergic inhibitors. Kidney Int 20:452–461, 1981 | PubMed | ISI | ChemPort |
  28. Badr KF, Gung A, Schreiner GF, Wasserman M: Reversal of antiglomerular basement membrane-antibody-induced fall in the glomerular ultrafiltration coefficient by leukotriene D4 antagonist SK & F 104353. (abstract) Kidney Int 31:363, 1987
  29. Lianos EA, Andres GA, Dunn MJ: Glomerular prostaglandin and thromboxane synthesis in rat nephrotoxic serum nephritis. Effects on renal hemodynamics. J Clin Invest 72:1439–1448, 1983 | PubMed | ChemPort |
  30. Andrews PM, Bates SB: Dietary protein prior to renal ischemia dramatically affects postischemic renal function. Kidney Int 30:299–303, 1986
  31. Ichikawa I, Purkerson ML, Yates J, Klahr S: Dietary protein intake conditions the degree of renal vasoconstriction in acute renal failure caused by ureteral obstruction. Am J Physiol 249:F54–F61, 1985
  32. Cochrane GC, Unanue ER, Dixon FJ: A role of polymorphonuclear leukocytes and complement in nephrotoxic nephritis. J Exp Med 122:99–116, 1965
  33. Cochrane CG, Müller-Eberhard HJ, Aikin BS: Depletion of plasma complement in vivo by a protein of cobra venom: Its effect on various immunologic reactions. J Immunol 105:55–69, 1970 | PubMed | ISI | ChemPort |

Extra navigation

.
ADVERTISEMENT