title: A single nephron model of acute tubular injury: role of tubuloglomerular feedback.
abstract: A single nephron model of nephrotoxic tubular injury was established to examine the mechanism whereby acute tubular damage contributes to reductions in nephron filtration rate (SNGFR). Acute microperfusion of 0.5 ng of uranyl nitrate (UN) into the early proximal tubule produced a significant reduction (16 to 30%) in SNGFR measured in both distal and proximal tubules of the same nephron and a decrease in absolute proximal reabsorption. Microperfused inulin was retained in the tubule suggesting this finding reflected a true reduction in SNGFR. Concurrent infusion of high dose furosemide (2 x 10(-4)M) and bumetanide (2 x 10(-5) M), but not low dose furosemide (2 x 10(-5) M), prevented the UN induced reduction in SNGFR. High dose furosemide begun after UN perfusion also prevented reduction in SNGFR. Continuous direct measurement of glomerular capillary hydrostatic pressure revealed no change. Distal intratubular Na+ and Cl- concentration increased significantly after UN perfusion. Activation of tubuloglomerular feedback mechanisms best explains the reduction in glomerular ultrafiltration that is characteristic of nephrotoxic forms of tubular injury.
authors.affiliation: Department of Medicine, University of California, San Diego, School of Medicine, La Jolla.
authors.forename: O W
authors.initials: OW
authors.lastname: Peterson
authors.forename: F B
authors.initials: FB
authors.lastname: Gabbai
authors.forename: R R
authors.initials: RR
authors.lastname: Myers
authors.forename: A P
authors.initials: AP
authors.lastname: Mizisin
authors.forename: R C
authors.initials: RC
authors.lastname: Blantz
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D005246:Feedback / Q000502:physiology; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007678:Kidney Glomerulus / Q000502:physiology*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000503:physiopathology; D007684:Kidney Tubules / Q000502:physiology*; D008297:Male; D051381:Rats; D014502:Uranyl Nitrate
chemical_list: D014502:Uranyl Nitrate; D005665:Furosemide