Glycerol-induced hemoglobinuric acute renal failure in the rat. I. Micropuncture study of the development of oliguria.

Abstract

The oliguria of acute renal failure has been attributed to tubular obstruction (1-12), "leakage" of the glomerular filtrate through rents in the tubular wall (13)(14)(15)(16)(17)(18)(19), and vascular mechanisms of various types (20)(21)(22)(23)(24)(25). In a previous paper, it was shown that the oliguria of mercury-induced acute renal failure in the rat reflects a primary decrease in glomerular filtration rate and cannot be attributed to tubular mechanisms (26). The applicability of these findings to most types of acute renal failure occurring in humans may be questioned, however, because of the very dissimilar etiologies and the known effect of large doses of mercury on the renal circulation (27). The present study concerns hours before glycerol injection. They lost an average of 8% of body weight in the period of dehydration, during which time their food intake was one-third less than that of nondehydrated animals. Blood samples were obtained by cardiac puncture from a number of glycerolinjected animals and dehydrated control rats that were exempted from micropuncture studies to determine the change in their blood urea nitrogen (BUN) occurring over a 48-hour period. BUN was measured on 0.2-ml samples by a modification of the urease method of Gentzkow (28). Urinary osmolalities were determined with an Advanced osmometer.Acute renal failure was induced by injecting 50%o glycerol in water into the muscle of both hind limbs at a total dose of 10 ml per kg of body weight. Within 2 hours after this injection, the urine was found to be burgundy red in color due to the presence of heme pigments.The animals were subjected to micropuncture experiments at times ranging from 30 minutes to 26 hours after glycerol injection. They were anesthetized with sodium pentobarbital given intraperitoneally at a dose of 40 to 50 mg per kg body weight. Their blood pressure was monitored as described earlier (26) either by a tail cuff microphone method or intra-arterial manometry. Although hypotension typically did not occur, animals whose mean arterial blood pressure was less than 85 mm Hg were excluded from micropuncture study. The left kidney was exposed through an abdominal incision and carefully dissected free of the perirenal fat. The renal hilus was disturbed as little as possible, and the renal capsule was left intact. The kidney was placed in a Lucite holder to minimize its displacement with respiration. Its surface was covered with warm mineral oil to prevent drying and to aid in visualization of the renal structures.Micropuncture methods were those described in an earlier paper (26). In short, proximal tubular hydrostatic pressure was measured by a modification of the manometric method of Wirz (29), using a water manometer to obtain maximal definition of the end point. The manometer was calibrated at zero pressure before each measurement. Glomerular filtration rate and fractional water absorption were determined at least 30 minutes after the injection of 40 ,uc of "C-labeled inulin 1 in 0.3 to 0.5 ml of 140 mM NaCl. Labele...

Micropuncture studies of proximal tubule albumin concentrations in normal and nephrotic rats

“…Anesthesia was induced by the intraperitoneal injection of sodium pentobarbital (50 mg/kg body weight). The animals were prepared for micropuncture studies as described previously (16). In brief, the kidney was exposed through an abdomino-flank incision, freed as gently as possible from the peri-renal fat, placed in a lucite holder, and covered with warm mineral oil.…”

Tubular von Hippel-Lindau Knockout Protects against Rhabdomyolysis-Induced AKI

“…[5][6][7][8] The animal model using an intramuscular glycerol injection with consequent myoglobinuria is closely related to the human syndrome of rhabdomyolysis. 9 Experimental data demonstrate renal vasoconstriction, 9-15 tubular hypoxia, 15,16 normal or even reduced intratubular pressure, [9][10][11] as well as large variation in single nephron GFR. 10,11 Intratubular myoglobin casts, a histologic hallmark, seem not to cause tubular obstruction, [9][10][11] but rather scavenge nitric oxide 17,18 and generate reactive oxygen species 19 followed by vasoconstriction.…”

The mechanism of acute renal failure after uranyl nitrate.

“…Recent studies on this issue (1-6) have suggested the following mechanisms leading to a reduction in measured filtration rate: (a) Renal vasoconstriction, which could decrease GFR by either a reduction in nephron plasma flow (rpf) or decrease the glomerular capillary hydrostatic pressure (Pa); (b) tubular obstruction may lead to a reduction in filtration by elevating tubular pressure and reducing the hydrostatic pressure gradient acting across the glomerular capillary membrane (AP) (4)(5)(6); and (c) transepithelial leak of solutes as large as inulin or lissamine green, as a result of epithelial injury, requiring no primary alteration in filtration at the glomerulus (7-9). The apparent disagreements which have arisen as to the exact mechanism for decreased GFR may have at least two explanations: (a) The experimental models which have been utilized differ rather markedly and (b) the experimental observations have been obtained at widely varied time intervals after the initial injury (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”