title: Dietary protein induces endothelin-mediated kidney injury through enhanced intrinsic acid production.
abstract: Dietary protein as casein (CAS) augments intrinsic acid production, induces endothelin-mediated kidney acidification, and promotes kidney injury. We tested the hypothesis that dietary CAS induces endothelin-mediated kidney injury through augmented intrinsic acid production. Munich-Wistar rats ate minimum electrolyte diets from age 8 to 96 weeks with 50 or 20% protein as either acid-inducing CAS or non-acid-inducing SOY. Urine net acid excretion and distal nephron net HCO3 reabsorption by in vivo microperfusion (Net J(HCO3)) were higher in 50 than 20% CAS but not 50 and 20% SOY. At 96 weeks, 50% compared the 20% CAS had higher urine endothelin-1 excretion (U(ET-1)V) and a higher index of tubulo-interstitial injury (TII) at pathology (2.25+/-0.21 vs 1.25+/-0.13 U, P<0.03), but each parameter was similar in 50 and 20% SOY. CAS (50%) eating NaHCO3 to reduce intrinsic acid production had lower Net J(HCO3), lower U(ET-1)V, and less TII. By contrast, 50% SOY eating dietary acid as (NH4)2SO4 had higher Net J(HCO3), higher U(ET-1)V, and more TII. Endothelin A/B but not A receptor antagonism reduced Net J(HCO3) in 50% CAS and 50% SOY+(NH4)2SO4 animals. By contrast, endothelin A but not A/B receptor antagonism reduced TII in each group. The data support that increased intake of acid-inducing dietary protein induces endothelin B-receptor-mediated increased Net J(HCO3) and endothelin A-receptor-mediated TII through augmented intrinsic acid production.
authors.affiliation: Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. donald.wesson@ttuhsc.edu
authors.forename: D E
authors.initials: DE
authors.lastname: Wesson
authors.forename: T
authors.initials: T
authors.lastname: Nathan
authors.forename: T
authors.initials: T
authors.lastname: Rose
authors.forename: J
authors.initials: J
authors.lastname: Simoni
authors.forename: R M
authors.initials: RM
authors.lastname: Tran
mesh_terms: D000141:Acidosis, Renal Tubular / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000143:Acids / Q000378:metabolism / Q000652:urine; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D000077300:Bosentan; D002364:Caseins / Q000008:administration & dosage / Q000633:toxicity*; D004044:Dietary Proteins / Q000008:administration & dosage / Q000633:toxicity*; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism / Q000652:urine; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D044022:Receptor, Endothelin A / Q000502:physiology*; D044023:Receptor, Endothelin B / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000143:Acids; D001639:Bicarbonates; D002364:Caseins; D004044:Dietary Proteins; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D019332:Endothelin-1; D010666:Phenylpropionates; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; C107831:darusentan; D000077300:Bosentan