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Nephrotoxicity of hemoglobin solutions.

M Feola¹, J Simoni, R Tran

¹Department of Surgery, Texas Tech University Health Sciences Center, School of Medicine, Lubbock 79430.

Biomaterials, Artificial Cells, and Artificial Organs

|January 1, 1990

Summary

Hemoglobin solutions (HbS) can cause kidney damage, but purification and crosslinking prevent this. Protecting kidneys with alkalinization or mannitol ensures safe hemoglobin-based oxygen carriers.

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Area of Science:

Biomedical Engineering
Nephrology
Pharmacology

Background:

Nephrotoxicity is a significant challenge for hemoglobin solutions (HbS) used as blood substitutes.
Understanding and mitigating HbS-induced kidney damage is crucial for clinical application.

Purpose of the Study:

To investigate the nephrotoxic potential of different hemoglobin solutions (HbS) in rabbits.
To identify key factors in HbS formulation that influence kidney function and histology.

Main Methods:

Five distinct HbS formulations were administered to rabbits, replacing one-third of blood volume.
Renal function was assessed via PAH clearance, creatinine clearance, fractional sodium excretion, and urine/plasma osmolarity.
Kidney histology was evaluated 24 hours post-administration.

Main Results:

HbS-I (impure, uncrosslinked), HbS-II (pure, uncrosslinked), and HbS-III (purified, crosslinked) showed significant nephrotoxicity.
HbS-IV (purified, crosslinked, pH 8.4) and HbS-V (purified, crosslinked, with mannitol) were well tolerated.
Nephrotoxicity decreased with increasing Hb purification and crosslinking.

Conclusions:

Complete purification and crosslinking of HbS are essential to prevent nephrotoxicity.
Alkalinizing urine (pH 8.4) or adding mannitol can further protect the kidneys from HbS-induced damage.
Optimized HbS formulations hold promise for safe blood volume replacement.