title: Acute-on-chronic renal failure in the rat: functional compensation and hypoxia tolerance.
abstract: BACKGROUND
  We hypothesized that chronic renal parenchymal disease may predispose to acute renal failure (ARF), facilitating the induction of hypoxic medullary tubular injury.
  
  
  METHODS
  To induce chronic renal parenchymal injury, rats underwent sham operation (control) or bilateral 50-min clamping of the renal artery [ischemia-reperfusion (IR)]. One or 3 months later, both groups were subjected to an ARF protocol, consisting of radiocontrast and the inhibition of prostaglandin and nitric oxide synthesis. Renal function and morphology were determined 24 h later.
  
  
  RESULTS
  Chronic tubulointerstitial changes (fibrosis, atrophy and hypertrophy) in the IR group correlated with baseline tubular function, but glomerular function was preserved. Functional deterioration after the ARF protocol was only marginally more pronounced in the IR group, and the degree of medullary acute tubular necrosis (ATN) was unaffected by prior IR. The extent of both tubular necrosis and chronic tubulointerstitial changes independently predicted the acute decline in renal function. Immunostaining of IR kidneys disclosed critically low medullary pO2 (determined by pimonidazole adducts), regional hypoxic cell response (hypoxia-inducible factors) and upregulation of endothelin-B receptors.
  
  
  CONCLUSIONS
  Compensatory changes result in normal plasma creatinine 1 and 3 months after IR, despite diminished tubular function. Preexisting renal disease only marginally predisposes to ARF, and the extent of ATN is not significantly enhanced. These findings illustrate the complex interaction between chronic and acute renal injury and dysfunction and parallel the difficulty of their assessment in the clinical practice. Adaptive cellular responses to chronic hypoxia in conjunction with parenchymal loss and decreased oxygen demand might alleviate acute hypoxic injury.
authors.affiliation: Nephrology Unit, Bikur Holim Hospital, Jerusalem, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Goldfarb
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenberger
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
authors.forename: Ahuva
authors.initials: A
authors.lastname: Shina
authors.forename: Fani
authors.initials: F
authors.lastname: Zilbersat
authors.forename: Kai U
authors.initials: KU
authors.lastname: Eckardt
authors.forename: Seymour
authors.initials: S
authors.lastname: Rosen
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Heyman
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology / Q000503:physiopathology*; D000222:Adaptation, Physiological; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000503:physiopathology; D007683:Kidney Tubular Necrosis, Acute; D007684:Kidney Tubules / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003404:Creatinine