The Renal Handling of Hemoglobin

Abstract

The glomerular filtration of hemoglobin (α2ß2) was studied under conditions in which its dissociation into αß dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of 59Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose.

Development of Recombinant Hemoglobin-Based Oxygen Carriers

“…These dimers pass through the kidney glomerular filters, resulting in an initial rapid clearance. Because the dimers are relatively unstable, autooxidation, hemin loss, and precipitation also occur, leading to obstruction of the kidney pores and oxidative stress with attendant renal failure (3,21,46,74,124). Another problem is that extracellular Hb rapidly scavenges endothelial NO and interferes with vasoregulation.…”

Inducible heme oxygenase in the kidney: a model for the homeostatic control of hemoglobin catabolism

“…Rat hemoglobin was obtained as outlined by Bunn, Esham, and Bull (11). Isotopically labeled rat hemoglobin was prepared by the method of Keene and Jandl (17) using 'FeCl3 (Tracer Lab, Waltham, Mass.)…”

“…Radioactivity excreted in the urine was compared with the excreted amount of hemoglobin, determined colorimetrically. Nine rats were depleted of their plasma haptoglobin (10,11) by two preliminary intravenous injections of 10 mg native hemoglobin spaced 1 hr apart. 1 hr later, each animal received intravenously, 2 mg of BME-treated or 2…”

“…As the kidney normally is not involved in the breakdown of red cells or hemoglobin, it expectedly has very low levels of heme oxygenase activity (5). However, in severe intravascular hemolysis, when hemoglobin released from circulating red cells exceeds the binding capacity of the plasma haptoglobin (10), unbound hemoglobin may be filtered by the renal glomeruli and appear in the urine (11). From the study of Bunn and Jandl (12), it would appear that in hemoglobinemia with hemoglobinuria, the kidney may be able to catabolize part of the filtered hemoglobin that has been reabsorbed by proximal convoluted tubules (13)(14)(15)(16).…”

Functional significance of glutamate–cysteine ligase modifier for erythrocyte survival in vitro and in vivo

“…Upon treatment with PHZ, free serum Hb (Figure 2a) was the consequence of severe oxidative damage to erythrocytes, leading to the immediate destruction of cellular integrity and release of Hb before the injured cell could be cleared from the circulation. Free serum Hb is filtered through the glomeruli of the kidney 17 and may accumulate and precipitate in renal tubules, thus reducing kidney function. 13,18 We therefore analyzed the kidneys from gclm þ / and gclm À / À mice at 24 h post-PHZ treatment.…”