title: Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia.
abstract: Ischemic nephropathy describes progressive renal failure, defined by significantly reduced glomerular filtration rate, and may be due to renal artery stenosis (RAS), a narrowing of the renal artery. It is unclear whether ischemia is present during RAS since a decrease in renal blood flow (RBF), O(2) delivery, and O(2) consumption occurs. The present study tests the hypothesis that despite proportional changes in whole kidney O(2) delivery and consumption, acute progressive RAS leads to decreases in regional renal tissue O(2). Unilateral acute RAS was induced in eight pigs with an extravascular cuff. RBF was measured with an ultrasound flow probe. Cortical and medullary tissue oxygen (P(t(O(2)))) of the stenotic kidney was measured continuously with sensors during baseline, three sequentially graded decreases in RBF, and recovery. O(2) consumption decreased proportionally to O(2) delivery during the graded stenosis (19 +/- 10.8, 48.2 +/- 9.1, 58.9 +/- 4.7 vs. 15.1 +/- 5, 35.4 +/- 3.5, 57 +/- 2.3%, respectively) while arterial venous O(2) differences were unchanged. Acute RAS produced a sharp reduction in O(2) efficiency for sodium reabsorption (P < 0.01). Cortical (P(t(O(2)))) decreases are exceeded by medullary decreases during stenosis (34.8 +/- 1.3%). Decreases in tissue oxygenation, more pronounced in the medulla than the cortex, occur despite proportional reductions in O(2) delivery and consumption. This demonstrates for the first time that hypoxia is present in the early stages of RAS and suggests a role for hypoxia in the pathophysiology of this disease. Furthermore, the notion that arteriovenous shunting and increased stoichiometric energy requirements are potential contributors toward ensuing hypoxia with graded and progressive acute RAS cannot be excluded.
authors.affiliation: Department of Physiology and Biomedical Engineering , Mayo Clinic, ST 7, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Lizette
authors.initials: L
authors.lastname: Warner
authors.forename: Sabas I
authors.initials: SI
authors.lastname: Gomez
authors.forename: Rodney
authors.initials: R
authors.lastname: Bolterman
authors.forename: John A
authors.initials: JA
authors.lastname: Haas
authors.forename: Michael D
authors.initials: MD
authors.lastname: Bentley
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.forename: Juan C
authors.initials: JC
authors.lastname: Romero
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005919:Glomerular Filtration Rate; D000860:Hypoxia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D017736:Ion-Selective Electrodes; D007511:Ischemia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007672:Kidney Cortex / Q000098:blood supply* / Q000378:metabolism; D007679:Kidney Medulla / Q000098:blood supply* / Q000378:metabolism; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D010101:Oxygen Consumption; D012078:Renal Artery Obstruction / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D012079:Renal Circulation; D012964:Sodium / Q000378:metabolism; D034421:Sus scrofa
chemical_list: D012964:Sodium; D010100:Oxygen