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266 DIETARY PROTEIN INDUCES REMNANT KIDNEY INJURY BY INCREASED INTRINSIC ACID PRODUCTION MEDIATED THROUGH ENDOTHELIN RECEPTORS.
  1. S. Phisitkul1,
  2. C. Hacker1,
  3. J. Simoni1,
  4. R. M. Tran1,
  5. D. E. Wesson1
  1. 1Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX

Abstract

Purpose We tested the hypothesis that acid-producing dietary protein induces endothelin-mediated parenchymal injury in the 5/6 nephrectomized rat by increasing intrinsic acid production.

Methods Munich-Wistar rats underwent surgical 5/6 nephrectomy (Nx) and were studied 12 weeks after eating diets with either acid-producing protein (casein) or non-acid-producing protein (soy). Intrinsic acid production in the casein group was reduced by added Ca++ citrate with Ca++ phosphate as a control. Intrinsic acid production in the soy group was increased by added (NH4)2SO4 with Na2SO4 as a control. Both casein-eating Nx and soy + (NH4)2SO4-eating Nx received either the oral endothelin A/B receptor antagonist bosentan or the oral endothelin A antagonist darunsentan. Distal nephron Net HCO3 reabsorption (Net JHCO3) was measured at 4 weeks by in vivo microperfusion. Urine endothelin 1 excretion (UET-1V), urine albumin excretion (UalbV), kidney glomerulosclerosis (GS), and tubulointerstitial injury (TII) were measured at 12 weeks.

Results (1) Casein-eating Nx versus soy-eating Nx had higher UET-1V (315 ± 52 vs 78 ± 13 fmol/d, p < .05), higher UalbV (180 ± 22 vs 74 ± 10 mg/d, p < .05), greater GS (2.8 ± 0.3 vs 1.5 ± 0.2 units, p < .05), and greater TII (3.5 ± 0.3 vs 1.9 ± 0.2 units, p < .05). (2) Casein-eating Nx additionally eating Ca++ citrate versus Ca++ phosphate had lower UET-1V (89 ± 22 vs 341 ± 56 fmol/d, p < .05), lower UalbV (105 ± 11 vs 177 ± 20 mg/d, p < .05), less GS (1.7 ± 0.1 vs 2.7 ± 0.2 units, p < .05), and less TII (2.2 ± 0.2 vs 3.3 ± 0.2 units, p < .05). (3) Soy-eating Nx additionally eating (NH4)2SO4 versus Na2SO4 had higher UET-1V (350 ± 40 vs 211 ± 26 fmol/d, p < .05), higher UalbV (145 ± 16 vs 86 ± 10 mg/d, p < .05), greater GS (2.4 ± 0.2 vs 1.6 ± 0.2 units, p < .05), and greater TII (2.8 ± 0.2 vs 2.0 ± 0.2 units, p < .05). (4) The endothelin A/B but not endothelin A antagonist reduced Net JHCO3 in acid-ingesting groups. By contrast, the endothelin A but not endothelin A/B antagonist reduced UalbV and TII in acid-ingesting groups.

Conclusions Acid-producing dietary protein induces endothelin B-mediated increased acidification and endothelin A-mediated TII in the 5/6 nephrectomized rat through increased intrinsic acid production.

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