Acute renal failure: definitions, diagnosis, pathogenesis, and therapy
Robert W. Schrier, … , Brian Poole, Amit Mitra
Robert W. Schrier, … , Brian Poole, Amit Mitra
Published July 1, 2004
Citation Information: J Clin Invest. 2004;114(1):5-14. https://doi.org/10.1172/JCI22353.
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Science in Medicine

Acute renal failure: definitions, diagnosis, pathogenesis, and therapy

Abstract

Acute renal failure (ARF), characterized by sudden loss of the ability of the kidneys to excrete wastes, concentrate urine, conserve electrolytes, and maintain fluid balance, is a frequent clinical problem, particularly in the intensive care unit, where it is associated with a mortality of between 50% and 80%. In this review, the epidemiology and pathophysiology of ARF are discussed, including the vascular, tubular, and inflammatory perturbations. The clinical evaluation of ARF and implications for potential future therapies to decrease the high mortality are described.

Authors

Robert W. Schrier, Wei Wang, Brian Poole, Amit Mitra

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Figure 7

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Hypoxic/ischemic proximal tubular necrosis results in activation of cyst...
Hypoxic/ischemic proximal tubular necrosis results in activation of cysteine protease pathways involving calpains and both caspase-1 (an inflammatory caspase) and caspase-3 (an executioner caspase involved in apoptosis). Calpain is activated both by increased free cytosolic Ca2+ and decreased calpastatin. Calpain then activates caspase-1, which stimulates the inflammatory cytokine IL-18. The executioner caspase-3 cleaves calpastatin (40).