Pathogenesis and Prevention of Acute Renal Failure
Abstract
Calcium channel blockers (CCB) including verapamil, nifedipine and emopamil, and calmodulin antagonists W-7 and trifluoperazine administered 1) in vivo, 2) in the isolated perfused kidney, 3) to isolated proximal tubules, or 4) to cultured tubules prevent or greatly attenuate O2 deprivation injury. Although the absolute decrease in adenosine triphosphate (ATP) and total adenine nucleotides that occurs in O2 deprivation injury is well known, this does not appear to be the sole or primary cause of injury since similar decreases can be achieved with glycerol or fructose and no injury is seen. However, the preservation of cellular ATP seen with fructose diphosphate treatment and the rapid return of ATP and adenine nucleotide levels to near normal is important in enhancing the recovery of renal function. Finally, verapamil and possibly other CCB may exert their effect on hypoxic tissue by reducing Ca uptake. The cellular accumulation of Ca during reoxygenation still is the most prevalent mediator of injury since blockade of this event with CCB, calmodulin binding drugs or low media Ca can all attenuate cell death. AP-III also exerts powerful protective effects on GFR in the intact rat previously exposed to a period of ischemia. The isolated perfused rat kidney was used to evaluate the protective effect of AP- III and, as in the intact rat, the principal effect was on improving GFR. Based on these impressive experimental results, we have begun studies in patients to evaluate the efficacy of using AP-III and calcium entry blockers to prevent ischemic (and other forms of) acute renal failure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 1987
- Accession Number
- ADA197237
Entities
People
- Robert W. Schrier
Organizations
- University of Colorado Boulder