摘要:

Cadmium is widely used in industry, causing exposure of workers and environmental pollution because of its persistence in the biosystems. Its very long half-life in the human organism causes its accumulation over the lifetime in liver and kidneys. Cadmium ions have a high affinity for tissue thiols, induce the synthesis of a carrier cysteine-rich polypeptide called metallothionein, and impair proteoglycan metabolism. Significant renal effects include early tubular nephropathy manifested by proteinuria, amino aciduria, glucosuria, phosphaturia, and calcium wastage. Chronic sequels include decrease in the glomerular filtration rate and increased risk of kidney stone disease. Biological monitoring of cadmium absorption includes determination of urinary cadmium and of low molecular weight marker proteins, such asβ2-microglobulin or retinol binding protein, the tubular reabsorption of which is impaired before a frank proteinuria.

ISSN:0886-022X    

DOI:10.3109/08860229509037613

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The presence of delayed graft function (DGF) following cadaver donor renal transplantation is associated with inferior graft survival as well as decreased patient survival. Delay in onset of function eliminates a valuable indicator of allograft viability, which is not easily replaced by standard diagnostic procedures. The purpose of this study was to demonstrate that a new clearance technique could be used to measure renal function minute to minute and under conditions similar to those observed in humans in the immediate posttransplantation period. A monkey model was used to provide controlled conditions. Increasing levels of ischemic injury were produced in 12 Rhesus monkeys by renal hilum cross-clamping. Real-time measurements of glomerular filtration rate (GFR) were obtained from the rate of clearance of the extracellular fluid of the GFR agent99mTc-DTPA, as measured with a specially designed external radioactivity counting device called the ambulatory renal monitor, or ARM. GFR was measured every 2–5 min as the slope (k) of the log of activity measured minute to minute versus time. GFR measurements were correlated with blood urea nitrogen (BUN), plasma creatinine (Cr), routine light microscopy, and measurement of proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Large changes in renal function due to ischemia or ureteral obstruction were observed within minutes. In addition, the rate constant on Day 1 was predictive of peak serum Cr (R = -0.86, R2=. 74, p =. 0001). Acute tubular necrosis (ATN) resolution was reflected more quickly when using the rate constant (Day 1) than when using either BUN or plasma Cr (Day 3–4). Because of renal functional reserve, BUN and plasma Cr were relatively insensitive indicators of mild to moderate reductions in GFR as compared with the rate constant. We conclude that ARM is a simple method which provides an accurate, near real-time GFR readout with potential applications not only for the clinical management of patients with DGF, but also as a research tool in acute renal failure (ARF).

ISSN:0886-022X    

DOI:10.3109/08860229509037614

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

This study in well-oxygenated, freshly isolated rat proximal tubules (RPT), examined the effects of several drugs that alter the transmembrane K+and Na+gradients across cell membranes, including valinomycin (VAL), amphotericin B (AMPHO), and ouabain (OUAB). The effects of high extracellular potassium chloride (KCl) concentration (45 mM) and low extracellular sodium concentration (100 mM) were also studied. After 10 min of drug exposure Ca2+uptake rate (nmol/mg/min) increased from 2.7 to 3.8 with VAL (p<. 02), from 2.9 to 3.7 with AMPHO (p<. 05), from 3.6 to 4.1 with OUAB (p<. 05), and from 3.2 to 4.8 with 45 mM KCl (p<. 001). Ca2+uptake rate was sustained at these high levels at 20 min in all treated RPT except those exposed to OUAB. LDH release averaged less than 15% in control tubules and did not increase significantly except in RPT treated with VAL, where LDH release at 10 min was 48% and at 20 min was 57% (both p<. 001). Of importance, only in VAL-treated RPT did ATP decrease to low levels (6.7 nmol/mg in control to 2.0±0.3 nmol/mg in VAL, p<. 001). Treatment with verapamil reduced Ca2+uptake rates at 10 min in VAL-treated RPT (from 3.8 to 3.1, p<. 02, in AMPHO-treated RPT (from 3.8 to 3.1 p<. 001), in OUAB-treated tubules (from 4.0 to 3.4, p<. 01), and in KCl-treated RPT (from 3.7 to 3.2, p<. 01). These results indicate that acute changes in the transmembrane ion gradient in RPT are accompanied by increased Ca2+uptake rates. Ca2+uptake rates are also increased during O2deprivation in RPT, a situation in which the transmembrane ion gradient is likewise altered. The increased Ca2+uptake rate observed in the present study and during hypoxia may have a common basis, that is, altered transmembrane ion gradients or some function thereof.

ISSN:0886-022X    

DOI:10.3109/08860229509037615

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The contribution of testosterone to the nephrotoxic effects of 1,2-dichloropropane (DCP) was assessed by a series of castration and sex hormone replacement experiments on Wistar rats. The nephrotoxic action of DCP was evaluated by measuring the accumulation of organic anion and release of aspartate aminotransferase into the incubation medium using a renal cortical slice model. Our data show that sex, castration, and testosterone pretreatment are factors that influence the effect of DCP on renal cortical slices of rats. Males appear to be more sensitive to nephrotoxic effects of DCP than females, male castration prevents the nephrotoxic effects of DCP, and pretreatment of females and castrated males with testosterone increases the susceptibility to DCP. In this study an attempt was made to evaluate the role of sex differences in the expression of enzymes participating in Phase I and Phase II detoxication reactions in order to explain the differences in sensitivity of the two genders to the nephrotoxic action of DCP. Our results implicate gender-specific expression of cytochrome P-450 in the kidney as a predominant factor that determines the different susceptibilities of male and female rats to the nephrotoxic effect of DCP. We propose that the oxidation of DCP by CYP IIE1 is the first saturable and limiting step in the metabolic activation of DCP to nephrotoxic metabolites. It appears that, despite the fact that the nephrotoxic effect of DCP is determined mainly by its cysteine-conjugated metabolites, glutathione (GSH) content and glutathione S-transferase (GST) activity in kidney are not directly related to increased androgen-related susceptibility to DCP. Since there were no significant differences in studied parameters of the liver in the genders, it is also possible to assume that DCP oxidative metabolism and glutathione conjugation in liver do not play an important role in the gender-specific susceptibility of rats to the nephrotoxic effect of DCP.

ISSN:0886-022X    

DOI:10.3109/08860229509037616

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

Weanling rats fed a methyl-deficient diet develop renal necrosis with acute renal failure. The aim of this experiment was to explore further the role of coconut oil in this experimental model. Weanling Wistar male rats were fed methyl-deficient and their controls were fed methyl-supplemented diets. Coconut oil was fed at 14% and 20%, the latter concentration with and without 1% safflower oil (rich in linoleic acid); other groups received similar diets but instead of coconut oil, a mixture of hydrogenated vegetable oil and corn oil (rich in unsaturated fatty acids) was employed. Coconut oil fed at a 14% concentration did not evidence any protective outcome in relation to the renal lesions. Coconut oil at a 20% concentration showed a protective effect, mainly when the diet included safflower oil. The renal protective effect was evidenced by less or no mortality and increased survival time in the methyl-deficient rats receiving coconut oil, as well as by a reduced incidence (%) and severity of the renal lesions as evaluated by renal weight, and type (tubular and cortical necrosis or repair) and extent (grade) of the renal damage. The lack of a protective outcome when coconut oil was fed at 14%, along with the fact that in those rats receiving coconut oil at 20% the protection was greater when the diet was supplemented with 1% safflower oil, indicates that the protective effect should be attributed to the type of fatty acids coconut oil has and not to their shortage of essential fatty acids.

ISSN:0886-022X    

DOI:10.3109/08860229509037617

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the renal toxicity caused by repeated injections of cis-diamminedichloroplatinum (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg) immediately after i.v. injection of DDP (20μmol/kg), and after 10 and 20 days they received repeated treatments with the same doses of DDP and BGD, Treatment with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated DDP injections increased lipid peroxidation in the kidney and decreased GSH concentration in the kidney at 5 days after the third injection of DDP. BGD treatment prevented the increase in lipid peroxidation and the decrease in the GSH concentration caused by repeated administrations of DDR. The determination of activities of antioxidant enzymes in the kidney showed that catalase activity decreased after repeated DDP administrations and that superoxide dismutase activity tended to decrease. Changes in activities of these enzymes were prevented by BGD treatment. The platinum concentrations in kidney and liver were decreased by BGD treatment. These results indicate that BGD treatment prevents the accumulation of platinum in the kidney after repeated administrations of DDP, resulting in protection against the DDP-induced renal toxicity.

ISSN:0886-022X    

DOI:10.3109/08860229509037618

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

ABSTRACTBACKGROUND: Diabetes insipidus renalis has only occasionally been reported in ifosfamide-induced renal Fanconis syndrome, but in two studies on subclinical renal impairment, low morning urine osmolarity was found in high frequencies. This study was performed to assess the frequency of defective concentrating capacity in patients with ifosfamide-induced renal Fanconi’s syndrome or severe impairment of proximal tubular function. PATIENTS AND METHODS: Seven patients with overt Fanconi’s syndrome and 5 with a generalized but subclinical tubulopathy were examined. Beside proximal tubular solute reabsorption and estimation of glomerular filtration rate, urinary osmolarity was measured after overnight fast and DDAVP (1-D-amino-8-D-arginine vasopressin) testing. RESULTS: Five out of 7 patients with overt Fanconi’s syndrome, but no patient with only subclinical tubular damage, had decreased osmolarities by at least one test. Increased sodium excretion was additionally found in 4 of these patients. CONCLUSION: Impaired renal concentrating capacity is a rare event in ifosfamide-induced renal dysfunction and confined to patients with overt Fanconi’s syndrome. These patients should, however, undergo evaluation of concentrating capacity and renal sodium handling as decreased concentrating capacity and increased sodium excretion would render a patient at risk for dehydration episodes.

ISSN:0886-022X    

DOI:10.1080/0886022X.1995.12098266

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

ABSTRACTHypertension, anemia, and arteriovenous shunts represent very important pathogenic factors in the occurrence of cardiovascular morbidity and mortality in patients with chronic renal failure. It can be expected that endothelin (ET), the most potent vasoconstrictor known at present, can react in a significant way to the hemodynamic changes caused by the construction of a vascular shunt or anemia. In 14 patients the plasma ET concentration was examined before and 24 h and 7 days after the construction of arteriovenous fistula. In 27 patients undergoing chronic hemodialysis treatment, ET was examined before the erythropoietin (EPO) therapy and after 2 months of EPO therapy, when partial correction of anemia had been achieved. The construction of arteriovenous fistula by itself had no significant influence on the plasma ET concentration. Subcutaneous application of EPO in doses that led to gradual correction of anemia was not accompanied by the rise of plasma ET. The average plasma concentration of ET was significantly higher in hemodialyzed patients, when compared to healthy controls as well as to patients with chronic renal failure before hemodialysis treatment was started.

ISSN:0886-022X    

DOI:10.1080/0886022X.1995.12098267

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

ABSTRACTThe aim of this study was the detection of HCV viremia in both anti-HCV antibody positive and negative hemodialysis patients. Sera from 75 patients on extracorporeal blood purification in the same dialysis unit were analyzed. Anti-HCV antibodies were detected using a 2nd-gene ration ELISA assay and in all positive cases a RIBA 3rd-gene ration test was performed. HCV-RNA was tested by a reverse transcription-nested polymerase chain reaction (RT-PCR) assay with primers located in the 5’region. PCR products were analyzed by a nonradioactive hybridation assay. The presence of anti-HCV antibodies was detected in 30 (40%) patients by means of ELISA II test; 28 of them were RIBA III positive and two indeterminate. Twenty-four of the 30 HCV Ab ELISA II positive patients (80%) were HCV-RNA positive (23 RIBA III positive and I indeterminate). Six anti-HCV Ab ELISA II positive patients tested negative for HCV-RNA (207c); 5 of these patients were also positive for anti-HCV antibodies with a RIBA III test and 1 was indeterminate. None of the anti-HCV negative patients was HCV-RNA positive. In two cases we documented the disappearance of viremia after an acute HCV infection, with the persistence of antibody reactivity. In conclusion, anti-HCV antibody positive hemodialysis patients should be considered as potentially infectious.

ISSN:0886-022X    

DOI:10.1080/0886022X.1995.12098268

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor

摘要:

ABSTRACTConventional urea kinetic modeling and peritoneal equilibration test (PET) were performed on 73 patients undergoing CAPD in order to determine factors influencing morbidity. Dialysis adequacy (KT/V, creatinine clearance, efficacy number) and nutrition (PCR, nPCR, creatinine generation rate, body mass index, albumin, transferrin) were compared to hospital admission days, blood pressure medication, and semiquantitative symptom indices. Renal clearance and dialysis intensity were the primary determinants of dialysis adequacy: patients without renal function required a dialysis intensity of>0.15 L/kg/day for adequate dialysis, while patients with a renal clearance>2 mL/min only required 0.1 L/kg/day. Ultrafiltration and PET played a minor role. High peritoneal equilibration rates (PER) were associated with increasing height, chronic glomerulonephritis, and recent peritonitis; low PER with polycystic renal disease and long CAPD duration (for patients without recent peritonitis). There were significant positive correlations between dialysis adequacy indices and nutritional indices: nPCR (p<0.001); creatinine generation rate (p<0.001), albumin (p<0.01), and negative correlations to symptom indices: fatigue (p<0.01), nausea (p<0.05), pain (p<0.05), and symptom index (p<0.01). Nutritional indices correlated negatively to morbidity indices: 1-year admission rate (p<0.01), pain (p<0.01), itching (p<0.05), edema (p<0.05). A high PER was a powerful and independent predictor of clinical morbidity: fatigue (p<0.01), nausea (p<0.01), pain (p<0.01), edema (p<0.05), symptom index (p<0.001), blood pressure medication (p<0.01), and 1-year admission rate (p<0.01). CONCLUSION: Adequate dialysis is difficult to obtain in CAPD patients with no renal function, and malnutrition is therefore common. Morbidity improves with increasing nutrition and dialysis intensity, there being no apparent plateau. Creatinine clearance and serum albumin are the most useful indices. A high PER paradoxically predicts a poor clinical outcome, due to increased loss of protein in the dialysate, poor ultrafiltration, and appetite suppression secondary to increased glucose absorption. Patients with a high PER should preferably be treated with nightly peritoneal dialysis or hemodialysis.

ISSN:0886-022X    

DOI:10.1080/0886022X.1995.12098269

出版商:Taylor&Francis    

年代:1995

数据来源: Taylor