Acute and long-term effects of modified hemoglobin (HBOC-201) in a rat model of hypertension and chronic kidney disease

BACKGROUND: The goal was to determine whether administration of the oxygen-therapeutic blood substitute HBOC-201 had any deleterious effect on renal function and/or structure in a rat model of chronic kidney disease (CKD). STUDY DESIGN AND METHODS: Longitudinal studies were conducted in the conscious chronically catheterized male Sprague-Dawley rat with rapidly progressing CKD produced by ablation-infarction of 5/6th of the functional renal mass. Experimental rats received a loading dose (after acute removal of 10% blood volume) and six subsequent daily maintenance doses of HBOC-201 at Weeks 4 to 5 after induction of CKD and were studied again at 6 weeks. Controls received isoosmotic human serum albumin (HSA, 13%) over the same period. Blood pressure (BP) and renal function were measured in acute experiments at Weeks 4, 5, and 6. Proteinuria and 24-hour creatinine clearance was measured longitudinally and renal pathology was assessed at killing. RESULTS: There were differences in the acute response to the infusions, with rats given HBOC-201 exhibiting an increase in BP and renal vascular resistance, whereas rats given HSA showed a decrease in BP. These changes did not persist, however, because mean BP, glomerular filtration rate, level of proteinuria, and glomerular pathology were all similar at the end of the study (6 weeks after induction of CKD) in rats given HBOC-201 and HSA. CONCLUSION: In this model of CKD, daily doses of HBOC-201 had no long-term damaging effects on renal function or structure, compared to rats given the osmotic control agent, 13 percent HSA.