Effects of single-dose infusion of pyridoxalated-hemoglobin-polyoxyethylene conjugate solution on canine renal...

Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP) is an acellular oxygen-carrying red blood cell substitute made from outdated human red blood cells. This study assessed the effect of PHP on renal function when PHP was infused with a clinically relevant dosage. A single dose of PHP that contains 8% wt/vol each of hemoglobin and maltose or an 8% maltose control solution was infused into the intact circulation of eight dogs (five dogs for PHP and three for the control; 20 ml/kg each, at the rate of 2.5 ml/h/kg for 8 h) in the awake state. Serial measurements of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out before and after infusion for up to 2 weeks, along with determinations of urine volume flow rate, fractional excretion of sodium (FES), and free water clearance (CH2O). The results showed an elevation of plasma colloid osmotic pressure by an average of 4.4 mm Hg immediately postinfusion with PHP solution. An average 23% decrease in GFR, without notable changes in RPF immediately postinfusion, was observed in the PHP group; the value returned to the preinfusion level by 1 week postinfusion. Increases in parameters such as urine output, FES, and CH2O, which were more pronounced in the PHP group, were observed for 24 h after the infusion in both groups. Light microscopic examination of kidney specimens taken at 2 weeks postinfusion revealed a slight degree of vacuole formation in approximately 80% of the proximal tubules in the PHP group. The tubules were devoid of typical pathologic features of acute renal failure, and the vacuoles did not cause any observable changes in the assessed tubular functions.