New features of renal lesion induced by stroma free hemoglobin

This study focused on the subacute renal lesions resulting from the infusion of stroma free hemoglobin (SFH), which remains under evaluation as a potential blood substitute despite limited renal toxicity observed in acute infusion. Four groups of rats received different doses of SFH (0.03, 0.48, 0.96, and 1.46 g, respectively) and were monitored, on alternate days, for their 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 renal morphology. The low dose (0.03 g) of SFH infusion did not alter the creatinine 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 necrosis was the most prominent renal lesion distributed in the proximal tubules, 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 mechanism of cell death. This study revealed for the first time proliferation of 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 toxicity indicated that a safety limit dosage for SFH infusion exists and that tolerance dose of SFH can be determined for clinical applications.