New features of renal lesion induced by stroma free hemoglobin

This study focused on the subacute renal lesions resulting from the infusio n of stroma free hemoglobin (SFH), which remains under evaluation as a pote ntial blood substitute despite limited renal toxicity observed in acute inf usion. Four groups of rats received different doses of SFH (0.03, 0.48, 0.9 6, and 1.46 g, respectively) and were monitored, on alternate days, for the ir glomerular filtration rate over the course of 10 days. Another group of 6 rats receiving 0.96 g SFH was sacrificed at day 10 for examination of ren al morphology. The low dose (0.03 g) of SFH infusion did not alter the crea tinine clearance (Clcr) over 10 days. The Clcr decreased in rats receiving 0.48 g SFH but fully recovered at day 10. A persistent decrease in Clcr was observed in the groups of rats receiving 0.96 and 1.68 g of SFH. Tubular n ecrosis was the most prominent renal lesion distributed in the proximal tub ules, especially in the convoluted segment of the juxtamedullary nephrons. Pearls' stained cytoplasmic granules and electron-dense lysosomal granules were found in surviving proximal tubules. Necrosis was the predominant mech anism of cell death. This study revealed for the first time proliferation o f smooth endoplasmic reticulum in the proximal tubules after SFH treatment, where it appeared as nodular aggregates of tubulovesicular structures. The effect of SFH on the proximal tubule appeared to be a direct toxicity, and this toxicity was shown to be dose dependent. The presence of reversible t oxicity indicated that a safety limit dosage for SFH infusion exists and th at tolerance dose of SFH can be determined for clinical applications.