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Results for “Uremia”

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At least 19 recordsLinked to original sources
PubMed1983

Immune response in experimentally induced uremia. V. Description of a model for chronic uremia in the rat that produces a long-term suppressive effect on T cell responses to mitogens.

This study describes a model for chronic uremia in the rat that produces a long-term suppressive effect on T cell responses to mitogens. We have found that (1) chronically uremic rats have significantly higher serum creatine levels than control rats and lymphocytopenia at all intervals tested after induction of uremia up to 4 1/2 months; (2) at all times tested after induction of uremia, the response of spleen cells from uremic rats to the T cell mitogens ConA and PHA was significantly suppressed as compared to control rats; (3) the severely suppressed response to PHA at all intervals tested after induction of uremia was eliminated by the removal of adherent spleen cells; and (4) adherent spleen cells, PMø, and AMø from chronically uremic rats are significantly more suppressive to control T cells than the corresponding control cells at all intervals tested after induction of uremia. Thus this animal model for chronic uremia is stable for at least 4 1/2 months and the effect of uremia on the response of lymphocytes to mitogens as well as on regulatory cells is not transient. Therefore this animal model can be used to study the effect of chronic uremia on the various parameters of the immune response.

Animals↗
PubMed1980

Experimental uremia. Description of a model producing varying degrees of stable uremia.

A model is described for the induction in the rat of varying degrees of stable uremia using controlled resection of renal tissue. Three degrees of uremia have been attained: 'mild--blood urea 40--80 mg/100 ml (6.68--13.36 mmol/1); 'moderate'--blood urea 100--200 mg/100 ml (16.7--33.4 mmol/1), and 'severe'--blood urea greater than 200 mg/100 ml (> 33.4 mmol/1). Mild uremia was produced by unilateral nephrectomy; moderate uremia required the resection of 80 +/- 2% of the total renal mass, and severe uremia was produced by 88 +/- 2% nephrectomy. A sham-operative procedure provided an appropriate control for the model. Evaluation of the model has been carried out using analyses of renal function (GFR, concentrating capacity), blood biochemistry, hematological parameters and histological examination. The ability to induce a standardized, stable uremia at predetermined levels, uncomplicated by the administration of nephrotoxic material, represents an advance on existing methods for producing experimental renal failure.

Animals↗
PubMed1983

Host immune status in uremia. V. Effect of uremia on resistance to bacterial infection.

Infection is a frequent complication and cause of death in renal failure. Although it is widely accepted that uremia has an adverse effect on host resistance to infectious disease, this association has not been proven. In the present experiments, the relationship between uremia and susceptibility to infection has been investigated using an animal model of chronic, severe uremia. Lung infections (using Pseudomonas aeruginosa and Klebsiella pneumoniae), bacteremia, peritonitis and subcutaneous infection (using Escherichia coli) were induced in uremic and normal rats and the course of infection compared. The ability of the uremic host to clear Ps. aeruginosa from the lung was marginally impaired in the first 24 hr after the challenge but was normal in the later stages of the infection. Similarly, in the bacteremia study, secondary invasion of the lungs by several other species of bacteria occurred in 33% of the uremic animals. We found no other evidence of impairment of immunity in uremia in the infections that we studied and, taken overall, the results support arguments that uremia per se is unlikely to be an important factor predisposing patients with renal failure to infection.

Animals↗
PubMed2002

The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia.

Cardiovascular disease is the leading cause of mortality in uremic patients. In large cross-sectional studies of dialysis patients, traditional cardiovascular risk factors such as hypertension and hypercholesterolemia have been found to have low predictive power, while markers of inflammation and malnutrition are highly correlated with cardiovascular mortality. However, the pathophysiology of the disease process that links uremia, inflammation, and malnutrition with increased cardiovascular complications is not well understood. We hereby propose the hypothesis that increased oxidative stress and its sequalae is a major contributor to increased atherosclerosis and cardiovascular morbidity and mortality found in uremia. This hypothesis is based on studies that conclusively demonstrate an increased oxidative burden in uremic patients, before and particularly after renal replacement therapies, as evidenced by higher concentrations of multiple biomarkers of oxidative stress. This hypothesis also provides a framework to explain the link that activated phagocytes provide between oxidative stress and inflammation (from infectious and non-infections causes) and the synergistic role that malnutrition (as reflected by low concentrations of albumin and/or antioxidants) contributes to the increased burden of cardiovascular disease in uremia. We further propose that retained uremic solutes such as beta-2 microglobulin, advanced glycosylated end products (AGE), cysteine, and homocysteine, which are substrates for oxidative injury, further contribute to the pro-atherogenic milieu of uremia. Dialytic therapy, which acts to reduce the concentration of oxidized substrates, improves the redox balance. However, processes related to dialytic therapy, such as the prolonged use of catheters for vascular access and the use of bioincompatible dialysis membranes, can contribute to a pro-inflammatory and pro-oxidative state and thus to a pro-atherogenic state. Anti-oxidative therapeutic strategies for patients with uremia are in their very early stages; nonetheless, early studies demonstrate the potential for significant efficacy in reducing cardiovascular complications.

Cardiovascular Diseases↗
PubMed2003

Calpain is activated in experimental uremia: is calpain a mediator of uremia-induced myocardial injury?

BACKGROUND: The cysteine proteases calpain and caspase-3 are known mediators of cell death. The aim of this study was to assess their contribution to the tissue damage found in experimental uremia. METHODS: Calpain and caspase-3 activities were measured in the hearts of rats that were sham-operated (control), sham-operated and spontaneously hypertensive (SHR), and those rendered uremic by 5/6 nephrectomy (uremic). In an in vitro study, heart myoblasts (Girardi) were incubated with human serum from healthy subjects (control serum conditioned media, CSCM) or uremic patients (uremic serum conditioned media, USCM), in the presence and absence of calpain and caspase-3 inhibitors. After 48 hours the activity of calpain and caspase-3 was measured, and cell injury determined by DNA fragmentation (ELISA) and lactate dehydrogenase (LDH) release. An in situ assay was designed to study how USCM affects calpain activity over time. RESULTS: In the in vivo study, mean calpain activities were almost identical in the control and SHR groups, but calpain and caspase-3 activities were much elevated in the uremic group (P < 0.01 and 0.001 respectively vs. control). The SHR group had significantly higher mean arterial blood pressure (P < 0.001 vs. control, 0.01 vs. uremic). In the in vitro study calpain activity and DNA fragmentation were markedly higher in USCM treated cells compared to CSCM (both P<0.05). Both were reduced in USCM cells containing calpain inhibitors (E64d, calpastatin, or PD 150606). LDH release was raised also in USCM treated cultures (P < 0.05), which only the E64d treatment could significantly reduce (P < 0.02). Caspase-3 activities were similar in USCM and CSCM groups. The in situ assay showed significant increases in calpain activity in USCM treated cells compared to CSCM after just 3.5 hours (P<0.01). CONCLUSIONS: In vivo results suggest that the increases in calpain and caspase-3 activity in uremic rat hearts were primarily due to uremia and not to hypertension. In vitro data demonstrate that uremia-induced cell injury can be attenuated by calpain inhibition. Therefore, it is likely that calpain is a mediator of uremia-induced myocardial injury.

Acrylates↗
PubMed2001

Paradox of risk factors for cardiovascular mortality in uremia: is a higher cholesterol level better for atherosclerosis in uremia?

Patients with chronic uremia have a substantially elevated risk of death from cardiovascular disease than do the general population. Although uremic and nonuremic groups share some of the risk factors for cardiovascular mortality, such as older age, diabetes, and inflammation, other factors appear to affect cardiovascular mortality in the opposite direction. For example, being overweight and having hyperlipidemia are established risk factors in the general population, whereas lower body mass index and lower plasma cholesterol have been shown to be risk factors for cardiovascular mortality in end-stage renal disease (ESRD). This paradoxical phenomenon is explained by two facts: (1) that malnutrition is a strong predictor of cardiovascular mortality in ESRD and (2) that plasma lipid levels are lowered in malnutrition. However, it is not known whether atherosclerosis is promoted by malnutrition or by low cholesterol level. Because the cardiovascular mortality rate is theoretically the product of event rate and fatality rate after an event, risk factors for cardiovascular mortality could fall into two categories: those raising the event rate and those affecting the fatality rate. Some factors could work both ways. Patients with ESRD show a significant increase in both event rate and fatality rate. Dyslipidemia is an independent factor affecting atherosclerotic arterial wall changes and cardiovascular events in ESRD. Other factors affecting the cardiovascular event rate in ESRD include diabetes and an elevated homocysteine level. In contrast, factors associated with poor survival after an event include diabetes and anemia. Malnutrition could be a factor causing the fatality rate to rise, although there is no direct evidence supporting this possibility. Further studies are needed to show the differential effects of a risk factor on event rate and fatality rate. Patients with ESRD would have a better chance of living longer by better management of the two categories of risk factors.

Arteriosclerosis↗