摘要:

Animal studies report equal or greater clinical efficacy with once daily versus multiple daily aminoglycoside dosing; however, results are inconsistent. Extrapolation of these animal data to human data is difficult, since marked variability exists in terms of pharmacokinetic disposition of aminoglycosides. Human data suggest that once daily aminoglycoside dosing regimens are as effective as multiple dosing regimens. However, studies need to be performed assessing the efficacy of once daily aminoglycoside dosing for infectious sites other than intra-abdominal and the urinary tract. In addition, the results of these studies should not be extrapolated to those with renal dysfunction, the immunocompromised, or in patients with aminoglycoside treatment durations of greater than 8 days, as the efficacy of once daily dosing in these patient populations has not been proven. Animal studies assessing nephrotoxicity suggest that multiple daily aminoglycoside dosing results in more frequent or more severe nephrotoxicity compared to once daily dosing. Nine human studies have been published comparing the nephrotoxicity of once daily versus multiple daily aminoglycoside dosing. The majority of investigators have studied nonimmuno-compromised patients with urinary tract infections. Netilmicin has been the most frequently used aminoglycoside, although other agents such as gentamicin, amikacin, and sisomicin have been studied. The most common netilmicin dosage regimen has ranged from approximately 4 to 6 mg/kg administered once daily. Eight of the nine trials performed have documented no significant differences in serial serum creatinine concentrations between once daily and multiple daily aminoglycoside dosing regimens, by the end of the study period. In conclusion, preliminary data suggest that once daily aminoglycoside dosing in nonimmunocompromised patients is equally efficacious and nephrotoxic compared to multiple daily dosing regimens.

ISSN:0886-022X    

DOI:10.3109/08860229209039110

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

It is well accepted that postischemic reperfusion promotes functional and morphological impairment which may be related to oxygen free-radical-mediated membrane damage. A new purified bioactive compound, calcitonin-gene-related peptide (CGRP), is known to be not only a potent vasodilator but also a cytoprotective agent. This study was designed to observe whether CGRP has a protective effect on the ischemic kidney. Male Sprague-Dawley rats were subjected to a 45-min period of renal ischemia followed by 60 min of reperfusion. At the beginning of the reperfusion, 12 rats were given intravenous saline and served as controls whereas 5 rats were given CGRP, 10μg/kg intravenously. After reperfusion the kidneys were removed for light- and electronmicroscopy, and the lipid peroxidation product malonaldehyde (MDA) was assayed by thiobarbituric acid (TBA) colorimetry. The results demonstrated that the serum creatinine (Scr) and renal MDA content in the CGRP group were significantly lower than those in the control group. The mean values for Scrwere 0.75±0.09 vs 0.93±0.05 mg/dL or 62.8±9.7 vs 82.2±4.4μmol/L (p>0.05), respectively; while the mean values for MDA were 18.71±2.13 vs 30.32±1.78 nmol/100 mg (ww) (p<0.05), respectively. The same signals of free radicals in the ischemic-reperfused kindey with or without CGRP were found by electron spin resonance. Morphological studies demonstrated that the treatment with CGRP ameliorated the ischemic-reperfusion injury to both renal brush borders and mitochondria. The results showed that CGRP has a protective action on ischemia-reperfusion renal injury by decreasing lipid peroxidation of membranes and suggest that it may be a beneficial agent for therapy of acute renal failure.

ISSN:0886-022X    

DOI:10.3109/08860229209039111

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The influence of amphotericin B on PAH transport as well as on lipid peroxidation in rat renal cortical slices was studied in vitro and ex vivo. In vitro, renal cortical slices were incubated with different amphotericin B (AmB) concentrations (2-60μg/mL) or with the corresponding vehicle concentrations of sodium deoxycholate (NaDo) (1.64-49.2μg/mL) and time dependency (15-30-60 min) with 30μg/mL AmB or 24.6μg/mL NaDo. Ex vivo, PAH transport of renal cortical slices was investigated following a 3-day intravenous AmB administration with 3 mg/kg per day or 2.46 mg/kg/day NaDo, respectively. In vitro AmB as well as NaDo decreased PAH transport dose and time dependency. At the highest AmB concentration of 60μg/mL, PAH uptake decreased to 17.6%. The corresponding NaDo concentration (49.2μg/mL) decreased PAH uptake to 33.3%. Time dependently AmB decreased PAH uptake to 25% after 60 min, NaDo caused a decrease to 69%. Administration of AmB for 3 days resulted in a PAH decline to 81%; NaDo decreased PAH uptake to 77%. In vitro as well as in vivo, AmB or its vehicle did not induce lipid peroxidation in renal cortical tissue. In summary, the results show that AmB and its vehicle, NaDo, decrease PAH uptake by renal cortical cells, reflecting a direct effect of AmB on tubular function. The impairment of the PAH transport is not due to enhanced lipid peroxidation.

ISSN:0886-022X    

DOI:10.3109/08860229209039112

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Na-coupled D-glucose transport in rabbits with cis-diamminedichloride platinum (CDDP; cisplatin) induced acute renal failure (ARF) has been studied. ARF occurred at 3 days after injection of CDDP (3 mg/kg i.v.). Na-coupled D-glucose transport into brush-border membrane vesicles (BBMV)from both outer cortex (OC) and outer medulla (OM) of ARF rabbits under zero-trans condition was decreased. Increased Km(i.e., decreased affinity of transport carrier for D-glucose) in OC and decreased Vmax(i.e., decreased number of glucose carrier) in OM were observed in CDDP-induced ARF rabbits. Decreased glucose transport was also observed under equilibrium exchange condition. Intravesicular volume of BBMV from OC and OM of ARF rabbits was decreased. In homogenate and BBMV from OC and OM of ARF rabbits, activities ofγ-glutamyl transpeptidase and alkaline phosphatase (marker enzymes of brush-border membrane) were decreased. Activities of succinate dehydrogenase, glucose-6-phosphatase, and Na-K ATPase (marker enzymes of mitochondria, endoplasmic reticulum, and basal lateral membrane, respectively) were not affected by CDDP administration. These results suggested that one of the main target sites of CDDP in kidney is brush-border membrane (BBM) along the proximal tubule, that is, not only Na-coupled D-glucose transport carrier protein but also other proteins in BBM.

ISSN:0886-022X    

DOI:10.3109/08860229209039113

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Experimental studies on mitomycin-C nephrotoxicity are scanty and mention the occurrence of cortical hemorrhage, tubular necrosis, or hydronephrosis secondary to papillomatous hyperplasia of the uroepithelium. To our knowledge, only one experimental study has mentioned morphological lesions similar to the hemolytic uremic syndrome in the human. In the present study 40 female Wistar rats were studied following unilateral renal perfusion of the left kidney with 2 mg/kg of mitomycin-C. Renal lesions corresponded to cortical necrosis with the presence of large bizarre nuclei. The presence of these nuclear atypias supports a direct toxic effect (alkylation) of the mitomycin or its metabolites on cells.

ISSN:0886-022X    

DOI:10.3109/08860229209039114

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Various biochemical parameters of renal tubular function were examined for a period of up to 12 weeks in rats rendered diabetic by an i.v. injection of streptozotocin. Except for a statistically significant decrease in the urinary excretion ofγ-glutamyl-transpeptidase to 64% of control values, the urinary excretion ofβ-N-acetyl-D-glucosaminidase,β-galactosidase, alanine aminopeptidase, and lactate dehydrogenase significantly increases in diabetic rats to betwen 154% and 712% of control values. This increased enzymuria is not correlated to the marked polyuria induced by diabetes (r between 0.14 and 0.35, not significant). Enzymuria is also accompanied by a 10-fold increase in the urinary excretion of the low molecular weight proteinβ2-microglobulin while the excretion of albumin is not significantly modified, indicating impairment of tubular reabsorption in diabetic animals. Clearance studies reveal that the clearance of bothβ2-microglobulin and infused egg-white lysozyme are also increased. Finally the histopathologic examination of paraffin sections of the kidney show hydropic degenerescence and pycnosis of the tubular cells. It is concluded that early-stage diabetes results in tubular impairment and that the streptozotocin-rat model appears well suited to the study of these early signs of renal dysfunction.

ISSN:0886-022X    

DOI:10.3109/08860229209039115

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Acute renal failure following hemorrhagic shock was studied in awake rats. The animals were bled to maintain the mean arterial blood pressure between 40 and 60 mm Hg during 180 min. After this period, the blood was reinfused and the rats were studied 24 h later. Hemorrhagic shock caused a less intensive renal injury than 60-min bilateral renal artery clamping. Renal function in the latter model was worse (p<0.05) as shown by serum creatinine (SCr) (0.75±0.10 vs 1.2±0.2 mg/dL), blood urea nitrogen (BUN) (26.0±2.8 vs 53.0±8.5 mg/dL), fractional excretion of sodium (FENa'%) (0.3±0.1 vs 1.8±1.0) and potassium (FEK'%) (41.4±5.7 vs 76.3±14.2) and urine/plasma creatine (U/PCr(86.4±15.7 vs 38.8±15.5). The rats which received verapamil (10μg/kg/min) prior and during the HS did not show increase in SCr(0.5±0.06 vs 0.75±0.1 mg/dL, p<0.05). This effect was also observed in the rats which received intravenous allopurinol (40 mg/kg) before HS, SCrdid not increase (0.5±0.04 vs 0.75±0.1 mg/dL, p = 0.05), suggesting a protective effect of those substances in HS. Otherwise, when higher doses (50 mg/kg) of allopurinol were injected intra-arterially before and after the HS there was marked worsening of the renal function (p<0.05), measured by SCr(1.5±0.3 vs 0.75±0.1 mg/dL), BUN (117.0±6.9vs 26.6±2.8 mg/dL), FENa(2.1±0.7 vs 0.3±0.1%), FEK(91.0±4.3% vs 41.4±5.7) and U/PCr(16.5±2.2 vs 86.4±15.7). The rats subjected to previous dehydration and pretreatment with gentamicin did not show worsening of renal function when subjected to HS. In conclusion, it was observed that 180-min HS in awake rats is a less intensive insult than 60-min bilateral renal artery clamping. The protective effect of verapamil and allopurinol in HS suggests the participation of cytosolic calcium and oxygen free radicals. However, higher doses of allopurinol given intra-arterially might cause ARF, instead of protecting against ischemia. Dehydration and pretreatment with gentamicin did not aggravate renal ischemia of the hemorrhagic shock.

ISSN:0886-022X    

DOI:10.3109/08860229209039116

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

Fourteen patients were studied 2 to 36 months after acute tubular necrosis. It was observed that 43% of the patients had decreased glomerular filtration rate. These patients were older and had lower urinary excretion of ammonium and titratable acidity. Proteinuria greater than 150 mg/day, without reaching a nephrotic level, was found in 92% of the patients. The presence of oliguria, the demand of dialysis, and the acute tubular necrosis etiology were not statistically different among the patients who recovered their glomerular filtration rate either totally or partially.

ISSN:0886-022X    

DOI:10.3109/08860229209039117

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The concentrations of urea, creatinine, and uric acid were measured in edema fluid and plasma during hemodialysis and 18 h after hemodialysis. The concentrations of these solutes in plasma were 15-17% lower than in the edema fluid after hemodialysis. Eighteen hours after hemodialysis, however, the concentrations in plasma were almost the same as those in edema fluid. These data suggest that the removal of these solutes from the extracellular space is delayed during hemodialysis. The plasma concentrations obtained at 18 h after hemodialysis are better indicators of hemodialysis efficiency.

ISSN:0886-022X    

DOI:10.3109/08860229209039118

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor

摘要:

The circadian rhythm (CR) of plasma renin activity (PRA), plasma aldosterone (PA), and plasma Cortisol (PC) was investigated in 8 patients with kidney transplantation, and in 10 patients with heart transplantation. Ten clinically healthy subjects were studied as controls. The transplanted patients were all under cyclosporine treatment associated with prednisone (PDN). Time-qualified levels of PRA and PA were seen to be higher than normal in both groups of transplanted patients. The analysis of PRA and PA circadian rhythm provided evidence for a systematically higher level of within-day concentrations. The higher level of oscillation suggests the occurrence of a condition of hyperreninemic hyperaldosteronism. The higher levels of PRA and PA 24-h values show no periodicity. The finding suggests the abrogation of the rhythmic function for renin-aldosterone system. The disappearance of PRA-PA circadian rhythm seems to be attributable to a side effect of immunosuppressive therapy.

ISSN:0886-022X    

DOI:10.3109/08860229209039119

出版商:Taylor&Francis    

年代:1992

数据来源: Taylor