title: The nature of renal cell injury.
abstract: The main functional change in patients with acute renal failure (ARF) is a decrease in glomerular filtration rate (GFR). The virtual complete recovery of renal function in those patients who survive ARF, as well as the minimal renal histological abnormalities during ARF when the GFR is less than 10 ml/min, suggest that a major component of the renal tubular cell injury is sublethal or reversible. Experimental models of acute tubular necrosis frequently have placed the emphasis on irreversible proximal tubular cell death. The nature of the renal tubular cell injury in ischemic acute renal failure, however, includes not only cell death (necrosis or apoptosis) but also sublethal injury causing cell dysfunction. The role of intracellular calcium, the calcium-dependent enzymes calpain, phospholipase A2 and nitric oxide synthase (NOS), in the pathophophysiology of this renal tubular cell injury during hypoxia/ischemia is described. The effects of calpain and nitric oxide (NO) on the cytoskeleton and cell adhesion are discussed. Potential mechanisms whereby tubular injury leads to a profound fall in GFR, including increased tubuloglomerular feedback and increased distal tubular obstruction, in ischemic acute renal failure are proposed.
authors.affiliation: Department of Medicine, University of Colorado School of Medicine, Denver, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Edelstein
authors.forename: H
authors.initials: H
authors.lastname: Ling
authors.forename: R W
authors.initials: RW
authors.lastname: Schrier
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000502:physiology; D016764:Cell Polarity; D006801:Humans; D007684:Kidney Tubules / Q000473:pathology* / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2
chemical_list: D009569:Nitric Oxide; D010741:Phospholipases A; D054467:Phospholipases A2; D002154:Calpain; D002118:Calcium