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).


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.


CONCLUSIONS
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.
Baylis
Chris
C
Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida 32610-0274, USA. baylisc@ufl.edu
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000009:adverse effects / Q000627:therapeutic use; D002908:Chronic Disease; D003401:Creatine / Q000652:urine; D004195:Disease Models, Animal; D006454:Hemoglobins / Q000008:administration & dosage / Q000009:adverse effects*; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy*; D007677:Kidney Function Tests; D008137:Longitudinal Studies; D008297:Male; D011507:Proteinuria; D051381:Rats; D017207:Rats, Sprague-Dawley
D001802:Blood Substitutes; D006454:Hemoglobins; C096798:HBOC 201; D003401:Creatine