CHRONIC-RENAL-FAILURE IS A STATE OF CELLULAR CALCIUM TOXICITY

Studies on the metabolic profile of many cells have shown that chronic renal failure (CRF) is associated with a significant elevation in the basal levels of cytosolic calcium ([Ca2+]i). This latter abnormality is, in major part, responsible for the organ dysfunction in CRF. The initial step leading to the eventual increase in the basal level of [Ca2+]i is parathyroid hormone (PTH)-mediated increased calcium influx into cells. This is followed by decreased extrusion of calcium out of cells due to reduced activity of the enzymes responsible for pumping calcium out of the cells. The combination of increased entry and decreased exit of calcium results in elevation of [Ca2+]i. Prevention of secondary hyperparathyroidism in CRF or blocking of the effect of PTH by a calcium channel blocker results in normalization of [Ca2+]i and restoration of cell function. Thus, the available data are consistent with the notion that CRF is a state of cellular calcium toxicity, which underlies many of the metabolic and functional derangements in CRF. © 1993, National Kidney Foundation, Inc.. All rights reserved.