The pathogenesis of glycerol‐induced renal tubular necrosis

Carroll, Robert G.; Kovács, K.; Tapp, E.

doi:10.1002/path.1700890216

Cited by 32 publications

(20 citation statements)

References 7 publications

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“…The mean pressure in 51 proximal tubules of ten dehydrated control rats was 15.0 + 0.2 cm HO, a pressure slightly less than that of nondehydrated control rats, significant at the 5% confidence limit (Figure 3). Fifteen (31)(32)(33)(34)(35)(36)(37)(38). The histologic lesions produced in this manner have been well described, and seem to be consistent from study to study.…”

Section: Resultssupporting

confidence: 58%

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

Oken¹,

Arce²,

Wilson³

1966

J. Clin. Invest.

217

126

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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...

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Section: Resultssupporting

confidence: 58%

“…Glycerol itself is not toxic to tubular epithelium (33,37), and hemoglobinuria per se has been shown not to cause acute renal failure in the rat (38,39). Carroll, KovAcs, and Tapp have postulated recently that glycerol predisposes to the development of acute tubular necrosis by producing a combination of hemoglobinuria and renal ischemia (38).…”

Section: Resultsmentioning

confidence: 99%

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

Oken¹,

Arce²,

Wilson³

1966

J. Clin. Invest.

217

126

View full text Add to dashboard Cite

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“…Alkaline diuresis has been shown to prevent the development of ARF that results from the injection of either haemoglobin or myoglobin in the rabbit (Baker & Dodds, 1925;Perri & Gorini, 1952) and both of these haemproteins have been implicated in the development of glycerol-induced ARF (Carroll et al, 1965;Preuss et al, 1975). Thus the alkalinity of the 8-PT vehicle may be a factor in this protective effect against ARF.…”

Section: Discussionmentioning

confidence: 99%

Effect of the adenosine antagonist 8‐phenyltheophylline on glycerol‐induced acute renal failure in the rat

Bowmer¹,

Collis²,

Yates³

1986

British J Pharmacology

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8‐Phenyltheophylline (8‐PT) (10 mg kg−1) or its vehicle (1 ml kg−1) were administered intravenously or intraperitoneally twice daily over 48 h to rats with acute renal failure (ARF) induced by intramuscular (i.m.) injection of glycerol. Rats treated with 8‐PT i.v. had significantly lower plasma urea and creatinine levels at 24 and 48 h compared to untreated animals. The vehicle also reduced plasma urea and creatinine when compared to untreated controls. However, plasma urea levels in 8‐PT‐treated rats were significantly lower than in vehicle‐treated animals at 24 and 48 h after both i.v. and i.p. administration. Plasma creatinine concentrations also tended to be lower in the 8‐PT‐treated group. [3H]‐inulin clearance at 48 h after i.m. glycerol was significantly greater in rats dosed i.p. with 8‐PT compared to either untreated or vehicle treated rats. Examination of kidneys taken from rats 48 h after i.m. glycerol showed that 8‐PT treatment significantly reduced renal damage and kidney weight compared to the untreated or vehicle‐treated groups. In a 7 day study all the rats which received 8‐PT i.p. survived whilst in the vehicle and untreated groups the mortality rates were 12 and 21% respectively. In a separate series of experiments 8‐PT (10 mg kg−1; i.v. or i.p.) was found to antagonize adenosine‐induced bradycardia in conscious rats for up to 5 h. There is no clear explanation for the partial protection afforded by the vehicle but it may be related to either its alkalinity or an osmotic effect produced by the polyethylene glycol component. The protective effect of 8‐PT in rats with ARF was probably the result of adenosine antagonism.

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“…He found that intraperitoneally administered glycerol failed to produce hemoglobinuria, yet it evoked a renal lesion identical histologically to that after glycerol injection by the subcutaneous or intramuscular routes. This question remains unresolved, however, since Carroll, Kovacs, and Tapp (14), using a larger dose of glycerol than that given by Finckh (13), did note hemoglobinuria associated with the renal lesion that followed intraperitoneal injection of glycerol. In any event, the lesion after glycerol injection appears to resemble morphologically that produced by nephrotoxic substances (15), and Oken and his co-workers have noted identical functional changes in that lesion and the one produced by mercury in the rat (1, 2).…”

Section: Discussionmentioning

confidence: 99%

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

Jaenike¹

1967

J. Clin. Invest.

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Summary. The role of renal ischemia in the pathogenesis of the renal failure produced by hemoglobin injection in the rat is evaluated. The data indicate that in the initial hours of this lesion renal blood flow is consistently reduced and that during its subsequent evolution blood flow rises towards normal levels, in some animals, while inulin clearance remains severely depressed. Volume expansion during the initial stage of the lesion may effect a rise in renal blood flow to normal levels with little effect on inulin clearance rate, further demonstrating the relative lack of dependence of the excretory defect on concomitant renal ischemia. These observations indicate that renal ischemia is probably a necessary factor in the initial production of the lesion; that it persists during its initial phase, up to 24 hours in most rats; and that, although it may contribute to the observed excretory defect, it is not the predominant etiologic factor.Other functional data indicate that renal blood is perfusing nephrons in which the excretory capacity is impaired but which retain the ability to extract Diodrast from the peritubular capillaries. This functional pattern indicates an excretory defect secondary either to intratubular obstruction or to a primary reduction of glomerular filtration rate of undefined etiology. The morphological findings of numerous dense intratubular hemoglobin casts and, in the well-perfused kidney, dilatation of proximal tubules, are suggestive of an obstructive lesion. However, the data do not conclusively distinguish between these two pathogenetic mechanisms. Introduction Acute renal failure in man occurs in a variety of clinical settings, reflecting the diversity of basic etiologic factors implicated in this syndrome. The

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The pathogenesis of glycerol‐induced renal tubular necrosis

Cited by 32 publications

References 7 publications

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

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

Effect of the adenosine antagonist 8‐phenyltheophylline on glycerol‐induced acute renal failure in the rat

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

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