The Renal Lesion Associated With Hemoglobinemia

Abstract

The precise mechanisms involved in the association of hemoglobinemia with acute renal failure remain unknown. The difficulties in studying this problem in patients are manifold, consequently the bulk of the investigation in this area has necessarily involved experimentally produced lesions in the laboratory animal. Largely as a result of such studies a variety of differing and conflicting hypotheses concerning the pathogenesis of this renal lesion have arisen. Perhaps the most favored of these are the suggestions that (a) tubular blockage by precipitated hemoglobin is the primary cause of excretory failure in the affected kidney, and (b) some undefined factor or factors produce a primary reduction in glomerular filtration rate, presumably as a consequence of renal ischemia. Carefully performed studies may be cited in support of either the first (1, 2) or second (3, 4) of these hypotheses. In addition, other explanations for the renal failure have been considered, particularly the role of abnormal back diffusion of tubular fluid through damaged tubular epithelial structures and the effect of renal edema in reducing renal blood flow and filtration rate. The establishment of an experimental model of a clinical renal disease in the laboratory animal affords the opportunity of making accurate functional measurements of the evolution of the lesion and of correlating structural alterations at each stage of the disorder with the corresponding functional data. This does not appear to have been accomplished with acute renal failure associated with hemoglobinemia. This lack of serial functional and morphological studies of a standard lesion may in part account for the conflicting views regarding the pathogenesis of this disorder. Consequently the present study was designed, with the ultimate objective of defining the mechanisms underlying the renal functional failure associated with this lesion.The present report describes a relatively simple method for the production of acute renal failure in the rat by the intravenous injection of hemoglobin. The lesion is reversible and relatively uniform in its functional and structural manifestations. Certain of the factors which influence its production and degree of severity have been examined. The functional evolution of the lesion, from its

The Renal Lesion Associated With Hemoglobinemia

“…This suggests a return of filtration in obstructed tubules, presumably also affecting patent tubules, since the measured inulin clearance rate has increased markedly at this time. This observation suggests that tubular obstruction may partially or wholly explain the persistent reduction in inulin clearance observed at 72 hr and beyond in this lesion (1). The suggestion that separate pathological processes may be involved in the evolution of this renal lesion is consonant with the biphasic character of the recovery of renal function in these animals (1).…”

“…The dogs used in Goldberg's study were normally hydrated and anesthetized with pentobarbital and consequently manifested normal renal blood flow and creatinine clearance just prior to hemoglobin administration. In the rat, employing the dosage of hemoglobin used in the present study, 40 rag/100 g, a functional defect is not produced under these experimental conditions (1). Although a relatively small amount of hemoglobin was used by Goldberg, 20 to 30 rag/100 g, this was infused into the aorta just proximal to the renal arteries so that presumably a very high concentration was transiently achieved in the renal artery and glomernlar filtrate.…”

“…The functional evolution of the lesion, from its time of onset to virtual recovery, has been characterized by the measurement of the inulin clearance rate (1). Histological studies at each stage of the lesion have also been performed, permitting a correlation of the morphological and functional alterations associated with this variety of acute renal failure.…”

“…A method has been established for the production of acute, reversible, renal failure in the rat by the intravenous injection of relatively small amounts of hemoglobin (1). The functional evolution of the lesion, from its time of onset to virtual recovery, has been characterized by the measurement of the inulin clearance rate (1).…”

The Renal Lesion Associated with Hemoglobinemia: A Study of the Pathogenesis of the Excretory Defect in the Rat*

“…The present study deals with an attempt to produce such a model by inducing acute renal failure associated with hemoglobinemia in the rat. The mode of production of this lesion, its functional evolution as defined by serial studies of inulin clearance rate, and certain of its morphological features have been previously described (4,5). These initial observations gave rise to the hypotheses that renal ischemia was an important factor in the initial stages of this lesion and that nephron obstruction by intratubular precipitates of hemoglobin was primarily responsible for the more protracted diminution in excretory function observed in these animals.…”