The Pathogenesis of the Renal Injury Produced in the Dog by Hemoglobin or Methemoglobin

Severe and persistent impairment of kidney function has been produced in dogs by intravascular hemolysis due to arsine, or by the intravenous injection of solutions of dog hemoglobin and methemoglobin. The kidneys of these animals have been examined by the usual histological methods and also by means of the ferrocyanide histochemical method to determine the pathogenesis of the renal injury. These observations indicate that obstruction to flow of urine through the renal tubules is an important factor in the early reduction of kidney function. The material filling the lumina of the renal tubules was found to be chiefly methemoglobin in concentrated solution of gel-like consistency. No evidence of formation of a pigment insoluble at the pH of the urine such as hemochromogen or hematin was found. The cessation of urine flow is most readily explained by the increased viscosity of the tubule contents. The intravenous administration of methemoglobin was found to produce more severe renal injury than the injection of equal amounts of oxyhemoglobin. Necrosis of the proximal convoluted tubule cells was present as a late lesion in animals injected with methemoglobin, large amounts of hemoglobin, or following extensive intravascular hemolysis. Such injury is probably a contributing factor in the persistent severe depression of renal function seen in these animals. Following disappearance of most of the intratubular pigment, a large number of collapsed tubules lined by hemosiderin-filled cells were found. The ferrocyanide histochemical studies indicated that these represented non-functioning nephrons although no obstructing intratubular material was present. Direct measurements in two animals failed to reveal any reduction of renal blood flow following the injection of methemoglobin in amounts sufficient to produce renal injury.