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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacokinetics of various doses (1-7.5 mg/kg i.v.) of indocyanine green (ICG) have been studied in control rats and rats with glycerol-induced acute renal failure (ARF). The pharmacokinetic changes seen at a dose of 1 mg/kg, after jugular vein administration, were significant decreases in uraemic rats in the rate of entry of ICG into the liver (k12) and in the rate of movement of dye from liver to plasma (k21). Greater and more numerous changes in pharmacokinetic parameters were recorded in experiments conducted using 4.0 and 7.5 mg/kg ICG. The results from these experiments showed that in addition to significant decreases in k12 and k21 there was a significant reduction in the rate constant for transfer of dye from liver to bile (k23). These changes were accompanied by a significant decrease in plasma clearance. In a separate series of experiments steps were taken to reduce the degree of uraemia produced by glycerol injection. The findings from these experiments showed no significant pharmacokinetic differences between control and mildly uraemic animals after administration of a dose of 7.5 mg/kg ICG. This suggests that the kinetic changes described above were a consequence of renal failure and not a direct hepato-toxic effect of glycerol.
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PMID:The plasma clearance of indocyanine green in rats with acute renal failure: effect of dose and route of administration. 663 79

The vascular reactivity of rats with glycerol-induced acute renal failure was assessed in vitro and in vivo. The contractile responses to noradrenaline, angiotensin and potassium chloride of aortic strips and portal vein segments from uraemic rats were significantly smaller than the responses obtained in vessels from control animals. The pressor responses to angiotensin were reduced significantly in rats with acute renal failure when compared to those in control rats. The reduced vascular responses to a range of spasmogens suggests that in this model of renal failure there is a defect in some mechanism of vascular contraction common to all three constrictor agents.
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PMID:Vascular reactivity in rats with glycerol-induced acute renal failure. 670 86

To elucidate abnormalities in the renal microvasculature that could account for the functional disturbances occurring in two well-established models of acute renal failure, we gave rats a single intramuscular injection of glycerol (50%, 10 ml/kg) or daily subcutaneous doses of gentamicin (100 mg/kg/day). Afferent arteriolar diameters were determined by measuring methacrylate vascular casts with SEM. The filtration barrier was examined by both SEM and TEM. The EF area was quantitated. By 3 hr, the glycerol treatment markedly decreased PADs and DADs (PAD 19.1 to 12.0 micrometers, DAD 13.8 to 7.4 micrometers, p less than 0.05). The changes were similar for both inner and outer cortical regions. By 3 days the vasoconstriction was alleviated; however, renal failure persisted. At that time, however, EF area was decreased to 43% of normal. After 10 days of gentamicin treatment, only minimal vasoconstriction occurred in the outer cortex; however, EF area was decreased to a similar degree as observed with the 3-day glycerol-treated animals. There are two phases to glycerol-induced acute renal failure. The first phase (described as readily reversible) is characterized by intense vasoconstriction. The second phase, which is not immediately reversible, is associated with a decreased EF area. Smaller outer cortical afferent arterioles and a decreased fenestral diameter and density of the glomerular endothelium are seen only after gentamicin-induced renal failure is well established (after 10 days of treatment).
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PMID:The morphology of the renal microvasculature in glycerol- and gentamicin-induced acute renal failure. 682 58

Carbamoylation of bovine and human albumin in vitro decreased the binding of methyl red and salicylic acid. Charcoal extraction of the carbamoylated albumin under acid conditions produced some decrease in the degree of carbamoylation, but did not substantially improve the binding of methyl red and salicylate. Albumin from rats with glycerol-induced renal failure showed no significant degree of carbamoylation compared to controls. Carbamoylation is not responsible for the binding defect of uraemic rat plasma, nor is likely to be involved in the case of human uraemic plasma.
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PMID:Drug binding defect of uraemic plasma: unlikely involvement of carbamoylated albumin. 713 74

cis-Diamminedichloroplatinum (CP), an important chemotherapeutic agent, produces acute renal failure by an unknown mechanism. Other heavy metals, such as mercury, are thought to be nephrotoxic by reacting with sulfhydryl (SH) groups. To investigate the mechanism of CP nephrotoxicity, F344 rats were injected once with 6 mg of CP per kg. After 96 hr, the blood urea nitrogen rose to 140 mg/100 ml. The SH concentration in control kidneys was 20.4 +/- 0.1 muml/g wet weight. Total renal SH groups decreased to a maximum of 14% at 120 hr (P less than .01). The fall in SH groups was entirely due to a decrease of protein-bound SH groups. Cell fractionation studies showed that the greatest decline of SH groups occurred in the "mitochondrial" and "cytosol" fractions. These fractions also had the highest Pt concentrations. There was no stoichiometric relationship between Pt accumulation and the change in SH groups. Furthermore, in vitro studies demonstrated that CP does not directly interact with SH groups. To determine if the change in renal SH groups was nonspecific effect of acute injury, renal failure was induced with glycerol (5 g/kg i.m.). Total SH groups per kidney increased after glycerol. These results indicate that the decrease in renal SH groups produced by CP is not due to nonspecific tubular necrosis. The present findings suggest the possibility that the nephrotoxic effects of CP may be related to depletion of SH groups. However, a direct cause-effect relationship has not been established.
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PMID:Mechanism of cis-platinum nephrotoxicity: I. Effects of sulfhydryl groups in rat kidneys. 719 25

There is considerable evidence that the principal functional abnormality in patients with acute reversible renal failure (ARF, or "acute tubular necrosis") is reduced cortical perfusion with diminished glomerular filtration. However, in such patients, high-dose intravenous urograms most commonly show an immediate obvious nephrogram. Since nephrographic density is believed to depend on the filtration of contrast medium into the tubular lumen, it is difficult to reconcile the early development of the nephrogram if glomerular filtration is reduced. Extensive experiments with both mercuric chloride and glycerol rat models of ARF have confirmed rapid intraluminal accumulation of contrast medium, albeit in reduced amounts. Studies using the normally filtered compound sodium nitroprusside and its precipitation as "prussian blue" suggest rapid transtubular diffusion from peritubular capillaries in kidneys with ARF. This, it is suggested, is also the mechanism for the rapid intraluminal ingress of contrast media and explains the early appearance of nephrogram. The less common intravenous urogram finding in ARF of a slowly developing and increasingly dense nephrogram may then represent cases with only slight tubular necrosis with predominant reduction in glomerular filtration.
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PMID:The functional basis for nephrographic patterns in acute tubular necrosis. 720 53

The hemodynamic alterations occuring in glycerol induced renal failure are controversial. To date no single humoral substance can fully explain the change in renal resistance observed in this hemodynamic model of acute renal failure. To assess the capacity of the rabbit kidney to produce thromboxane A2, a potent vasoconstrictor, the following experiments were carried out. Rabbits received 14 ml/kg of 50% glycerol subcutaneously 24 hrs before the study. After 24 hrs., the kidneys were removed and perfused ex vivo in superfusion bioassay cascade. Kidneys from rabbits which developed renal failure, as assessed by elevated serum creatinines, released a substance which produced contraction of rabbit aorta (RCS) in response to bradykinin (BK) and angiotensin II. Microsomes prepared from these kidneys when incubated with [14C]-arachidonic acid produced a peak of radioactivity which comigrated with thromboxane B2 on the thin layer chromatography and was inhibited by the thromboxane synthetase inhibitor imidazole. Furthermore, an inverse linear relation was found between the BK dose required to release RCS from perfused kidney and the serum creatinine levels. A direct linear relation was found between the percent of TxB2 produced by renal microsome preparations and the serum creatinine. These studies demonstrate an increased renal capacity of the glycerol-model of acute renal failure to produce TxA2. The production of TxA2 a potent vasoconstrictor should therefore be further evaluated as a potential endogenous mediator of the hemodynamic changes occurring in acute renal failure.
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PMID:Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure in the rabbit. 738 43

Cardiac output and liver blood flow were measured using 15-micron diameter radioactive microspheres in anaesthetized male rats 12, 24 and 48 h and 7 days after induction of acute renal failure with glycerol. Plasma urea concentration was greatest in those rats studied 48 h after glycerol injection and at 7 days animals could be divided into 'recovering' and 'azotemic' on the basis of plasma urea levels. Cardiac output was significantly lower at 12 h than that found in control rats, but it was significantly greater than control values in azotemic animals at 48n h and in the 'recovering' group of rats at 7 days. Changes in cardiac output did not correlate with alterations in haematocrit. Liver blood flow showed a number of changes in the azotemic animals relative to the control rats; at 12 h it was significantly lower in the glycerol-treated rats whilst it was increased at 48 h and in both groups of animals at 7 days. When the proportion of cardiac output distributed to the liver was determined using 50-micron diameter microspheres, it was not significantly different from that determined using the smaller microspheres at 12 and 48 h after glycerol injection. This indicates that the results with the smaller microspheres were not distorted by incomplete trapping in the hepatic and splanchnic vascular beds. The implications of altered liver blood flow for drug metabolism in renal failure are discussed.
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PMID:Alterations in liver blood flow during glycerol-induced acute renal failure in the rat. 742 52

Ischemic brain edema promotes focal cerebral ischemia by increasing intracranial pressure and thereby reducing perfusion pressure, obstructing capillaries and prolonging transport routes within ischemic tissue. There is clinical and experimental evidence that osmotic agents counteract these mechanisms. Moreover, glycerol may act as a free radical scavenger, antioxidant, and activator of plasma prostaglandin (PGI2), resulting in vasodilation. Improvements in ischemic brain energy metabolism after glycerol administration has also been postulated. Results of clinical trials on glycerol treatment of acute ischemic stroke were not conclusive: some demonstrated improved survival in the acute stage, in others survivors benefited in terms of neurological status and/or daily living activities. Other trials did not reveal any superiority of glycerol treatment over placebo. Glycerol is given intravenously as a 10% solution or orally. By the oral route higher intravascular glycerol concentration can be achieved with smaller quantities of fluid. Possible side effects include elevation of blood glucose level with subsequent lactate acidosis in the ischemic brain, serum hyperosmolarity after long-term glycerol administration and--when given intravenously--volume overload in patients with congestive heart failure and hemolysis that may cause renal failure.
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PMID:[Treatment of ischemic cerebral infarct with glycerine]. 756 70

Rhabdomyolysis and other causes of massive myoglobin release are often complicated by an acute ischemic renal failure. We tested the hypothesis that endothelin-1, the most potent renal vasoconstrictor known, plays a role in the renal toxicity of myoglobin. For this purpose, we induced rhabdomyolysis (8 ml/kg i.m. of a 50% glycerol solution) in rats pretreated or not pretreated with bosentan, a novel potent nonpeptide endothelin receptor antagonist. Glycerol decreased renal function dramatically, increased proteinuria and induced a massive tubular necrosis. This effect was associated with a 22% increase in plasma endothelin concentration. Bosentan prevented the decrease in creatinine clearance (1.12 +/- 0.07 ml/min vs. 0.83 +/- 0.05 ml/min, P < .01), the increase in proteinuria (19.9 mg/24 hr vs. 31.8 mg/24 hr, P < .001) and the tubular necrosis induced by glycerol (as assessed by histopathological evaluation), without affecting myoglobinuria. Involvement of endothelin was further suggested by the observation that myoglobin could markedly increase endothelin-1 release by rat mesangial cells in culture. We conclude that endothelin is, at least in part, responsible for the massive tubular necrosis observed in myoglobinuric nephropathy.
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PMID:Role of endothelin in acute renal failure due to rhabdomyolysis in rats. 761 35


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