Structural changes in the perfused canine kidney exposed to the direct action of endotoxin

We attempted to clarify whether structural damage or hemodynamic alterations is the primary cause of renal failure in the initial phases of endotoxic shock. Endotoxin (0.5 mg/kg) was infused directly into the renal artery and normal renal hemodynamics were maintained by cross-perfusion and controlled pressure. Direct exposure of renal parenchyma to endotoxin action was followed by changes in structure at the cellular and subcellular levels. The damage was unequally distributed and involved mainly the mitochondria and lysosomes of the distal and proximal convoluted tubules. No significant structural changes could be detected in the glomeruli or in the vascular compartment. There was no direct relationship between the degree of mitochondrial and lysosomal damage and the changes in enzymatic activity. The enzymatic systems associated with active Na transport and glycogen breakdown showed only slight alterations, while those related to energy production, hydrogen transfer and the respiratory activity of the cell were severely affected. These results indicate that structural damage in the nephron may contribute to the renal failure in the initial phase of endotoxemia.