Renal effects of a pyridoxalated-hemoglobin-polyoxyethylene conjugate solution as a blood substitute in exchange transfusions.
With PHP as an oxygen carrier, histologic studies in ET showed changes of renal tubular epithelial cells at 2 weeks post ET, with normal structure by 3-12 months post ET. The renal functional effects of PHP were evaluated by ET (30%, N = 3; 50%, N = 1; 80%, N = 3) in seven healthy mongrel dogs. Blood, urine, and renal biopsy specimens were taken pre ET and at 0, 1, and 2 days, 2, 4, and 6 weeks, and 3, and 6 months post ET. Data were compared to modified criteria of acute tubular necrosis. All dogs tolerated the procedure well and survived for 1 year. Urine output was normal with elevation during the first 2 days in the 50 and 80% ET, followed by stable output by 2 weeks, ranging from 12 to 60 ml/kg/day. Blood urea nitrogen (BUN) and serum creatinine (SCr) were normal. BUN/SCr was normal. The urine to plasma osmolality ratios were 2.6 to 8.3 (normal greater than 1), and fractional percent excretions of sodium (FES) were stable throughout. No existence of broad granular pigmented casts (BGPC) in urine sediment were noted. Renal histologic evaluation of vacuolization in the renal tubules were seen to be dose-dependent and transient, with normal histology by 3-6 months post ET. Dose-dependent vacuole formation observed in the early weeks post ET with PHP showed no renal functional changes. Based upon the modified criteria for acute tubular necrosis, no histologic abnormalities were noted.
Matsushita
M
M
Department of Artificial Organs, Cleveland Clinic Foundation, OH 44106.
Yabuki
A
A
Chen
J F
JF
Takahashi
T
T
Harasaki
H
H
Malchesky
P S
PS
Iwashita
Y
Y
Nosé
Y
Y
D000818:Animals; D001802:Blood Substitutes / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005078:Exchange Transfusion, Whole Blood; D006454:Hemoglobins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000187:drug effects / Q000648:ultrastructure; D011092:Polyethylene Glycols / Q000494:pharmacology*; D014617:Vacuoles / Q000648:ultrastructure
D001802:Blood Substitutes; D006454:Hemoglobins; C050907:pyridoxalated-hemoglobin-polyethylene glycol conjugate; D011092:Polyethylene Glycols