The role of cell calcium overload in nephrotoxic renal tubular cell injury.

Abstract

Data on the role of cell Ca++ overload in the pathogenesis of nephrotoxic renal tubular injury and methodologic considerations for studying this process were reviewed. It was concluded that: A consistent pattern of Ca++ uptake and resultant functional changes are attributable to the interactions of Ca++ with mitochondria during their isolation, unless specific measures are taken to prevent these interactions. The simplest approach to prevent in vitro Ca++ from occurring during isolation of mitochondria from injured tissues having high Ca++ levels is to include ruthenium red in the homogenizing solution used to prepare the mitochondria, although this will still permit some surface binding of Ca++ to mitochondria. By comparing mitochondrial Ca++ levels and functional parameters of mitochondria isolated after in vivo nephrotoxic injury with those of control mitochondria isolated at similar homogenate Ca++ levels, the components of mitochondrial Ca++ overload and functional deterioration solely attributable to in vivo events can be identified. These were detailed for gentamicin- and mercuric chloride-induced nephrotoxicity. Tissue and mitochondrial Ca++ overload are relatively late events during the development of renal tubule cell injury secondary to aminoglycosides or to mercuric chloride, occurring only when lethal cell injury is present by morphologic criteria. Since it correlates with lethal cell injury, the presence of tissue Ca++ overload can be of value in assessing this process, but care must be exercised in drawing conclusions about the extent of lethal cell injury, because the degree of Ca++ overload can be modified by factors, such as saline intake, independently of changes in the number of lethally injured cells.