Cellular mechanism of ischemic acute renal failure: Role of Ca2+ and calcium entry blockers

Summary This presentation briefly reviews the cellular mechanism of ischemic acute renal failure (ARF) with particular emphasis on the role of Ca²⁺ and calcium entry blockers (CEB). Vascular consequences of an ischemic renal insult including vasoconstriction, diminished glomerular permeability, loss of autoregulation, and hypersensitivity to renal nerve stimulation may relate to increased cellular Ca²⁺ concentration in the renal afferent arteriole and glomerular mesangial cells. Evidence is also presented that the ischemic injury to tubular plasma membranes is associated with increased Ca²⁺ uptake. With an ischemic insult of a short duration, the renal mitochondria are able to buffer the increased cellular Ca²⁺. However, after an ischemic insult of long duration, the Ca²⁺ overloaded mitochondria deteriorate, adenosine triphosphate (ATP) synthesis decreases, and cell death follows. If a sufficient number of renal tubular cells undergo this cell death, tubular obstruction, i.e. the maintenance phase of ARF, occurs.