title: Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.
abstract: BACKGROUND
  Recent experimental work suggests a paradox: although uremia evokes systemic toxicities, in the setting of AKI, it can induce intrarenal cytoprotective and anti-inflammatory effects. Whether these influences can attenuate post-ischemic kidney disease progression remains unknown.
  
  
  METHODS
  To explore this possibility, male CD-1 mice were subjected to a 30-min unilateral (left) kidney ischemia model, previously shown to reduce renal mass by ∼50% over 2-3 weeks. Stepwise azotemia/acute uremia was superimposed by inducing different lengths of contralateral (right) kidney ischemia (0, 15, 18, 20 min). Subsequent loss of left renal mass (kidney weight) was assessed 2 weeks later and contrasted with the degree of initial azotemia 24-h BUN.
  
  
  RESULTS
  A striking correlation between 24-h BUNs and 2-week left renal mass was observed (r, 0.77; P < 0.001). With 20 min of right kidney ischemia, left kidney size was completely preserved. This preservation did not result from increased tubular cell proliferation or decreased microvascular loss, as gauged by KI-67 and CD-34 immunohistochemistry, respectively. Rather, an early reduction in proximal tubule cell dropout (as judged by renal cortical N-acetyl-glucosaminidase content), with a subsequent preservation of tubule mass, was observed.
  
  
  CONCLUSIONS
  In summary, these findings advance a novel concept: acute uremia can confer early post-ischemic cytoprotection resulting in a slowed progression of post-ischemic kidney disease.
authors.affiliation: Department of Medicine, University of Washington, and the Fred Hutchinson Cancer Research Center, Seattle, WA, USA. dzager@fhcrc.org
authors.forename: Richard A
authors.initials: RA
authors.lastname: Zager
authors.forename: Ali C
authors.initials: AC
authors.lastname: Johnson
authors.forename: Kirsten
authors.initials: K
authors.lastname: Becker
mesh_terms: D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D053099:Azotemia; D007124:Immunoenzyme Techniques; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D012079:Renal Circulation; D015427:Reperfusion Injury; D014511:Uremia
chemical_list: D000118:Acetylglucosaminidase
keywords: KI-67; MCP-1; N-acetyl glucosaminidase; acute kidney injury; chronic kidney disease
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