Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic renal failure (CRF), the ATP-dependent, ubiquitin-proteasome proteolytic pathway is activated with concurrent increases in the transcription of genes encoding proteins of this pathway in muscle. We have shown that the stimuli for these responses include acidosis and glucocorticoids, but other endocrine abnormalities in CRF (e.g., insulin resistance) could contribute to these responses. In fact, a major effect of insulin in muscle is to suppress protein degradation. To examine whether insulin influences the ubiquitin-proteasome pathway, we measured protein degradation in incubated epitrochlearis muscles of diabetic and pair-fed control rats. Muscle proteolysis was increased in pathways that do not involve lysosomes or Ca(2+)-dependent proteases; but MG132, a protease inhibitor that blocks ATP synthesis, eliminated the accelerated rate of protein degradation in diabetic rat muscles. Diabetes mellitus also increased levels of mRNAs encoding ubiquitin (334%), E2 ubiquitin-conjugating enzyme (247%), and the C3 (320%), C5 (349%), and C9 (216%) proteasome subunits in muscle. Finally, transcription of the ubiquitin gene in diabetic rat muscles was increased. Diabetic rats were acidotic, but eliminating acidemia by giving NaHCO3 did not block the increase in muscle proteolysis. Giving diabetic rats insulin prevented the excessive muscle proteolysis, suggesting that insulin acts as a suppressor of the ubiquitin-proteasome pathway. Thus, the insulin resistance of uremia could contribute to muscle protein wasting in CRF.
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PMID:Signals regulating accelerated muscle protein catabolism in uremia. 938 16

Nephrotic syndrome is a protein-wasting disorder affecting total body protein metabolism, often leading to reduction of lean body mass and changes of muscle cell composition. The aim of this study was to investigate the susceptibility to muscle cell damage in nephrotic patients following submaximal physical exercise, by detection of the creatine kinase (CK) plasma level changes. Fourteen patients affected by primary nephrotic syndrome, without chronic renal failure, underwent an exercise test on a cycle ergometer for 20 min at a constant speed (60 rpm). In each subject, the work rate (expressed as watts) was established as 70% of the maximum power theoretically calculated on a sex, age, weight and height basis. CK plasma levels (U/l) were determined before and 1, 3, 6 and 24 h after the exercise. Following exercise, CK plasma levels became higher in nephrotics than in normal controls. That is, the amount of CK increments was greater in nephrotics than in controls from the first hour after the end of exertion. These changes, both as absolute values and as percentage of the basal values, correlate positively to daily urinary protein losses; moreover, an inverse relationship was detected with albumin serum levels. However, no correlation was observed between the amount of plasma CK increases and age, body weight, plasma creatinine, plasma cholesterol or hemoglobin levels. These results demonstrate that a greater than normal increase of CK plasma levels occurs in nephrotics following physical exercise, and that this increment correlates with the severity of urinary protein wasting. This suggests an increased susceptibility to muscle injury in nephrotic patients probably related to protein depletion and/or to modifications of muscle cell metabolism. Further studies are needed to define the pathogenesis of our findings.
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PMID:Abnormal increase of creatine kinase plasma levels following muscle exercise in nephrotic patients. 973 21

Many factors contribute to the growth failure of chronic renal failure: water and electrolytes disturbances, hypertonicity, phosphate or calcium wasting, secondary hyperparathyroidism, anemia, hypertension, metabolic acidosis, and malnutrition. In addition, the pubertal growth spurt is usually stunted. Growth hormone (GH) resistance is observed with low GH binding protein (GHBP) level, and normal or low IGF I levels despite elevated GH level. Elevated IGFBP levels may contribute to a reduced IGF activity, especially in dialysed patients. Glucocorticoid therapy in transplanted patients further contribute to poor growth and inhibited IGF I activity. As conventional treatments have a limited effect to improve growth, adult height is often far below -2 SD. GH therapy has proved to be successful, especially in young children, overpassing the hormonal resistance so that an adult height within the normal range may be reached.
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PMID:[Physiopathology of the somatotropin axis in chronic renal insufficiency]. 985 82

There is a high prevalence of protein-energy malnutrition in both nondialyzed patients with advanced chronic renal failure and in those individuals with end-stage renal disease who are receiving maintenance hemodialysis or chronic peritoneal dialysis therapy. Approximately one-third of maintenance dialysis patients have mild to moderate protein-energy malnutrition, and about 6 to 8 percent of these individuals have severe malnutrition. These statistics are of major concern because markers of protein-energy malnutrition are strong predictors of morbidity and mortality. The causes of protein-energy malnutrition in patients with chronic renal failure include: (1) decreased energy or protein intake; (2) concurrent chronic illnesses, and superimposed acute illnesses and possibly increased inflammatory cytokines; (3) the catabolic stimulus of hemodialysis; (4) losses of nutrients into dialysate, particularly amino acids, peptides, protein (with peritoneal dialysis), glucose (when hemodialysis is performed with glucose-free dialysate) and water-soluble vitamins; and (5) diagnostic or therapeutic (e.g., prednisone therapy) procedures that reduce nutrient intake or engender net protein breakdown. Other theoretically possible causes for protein-energy malnutrition include (6) chronic blood loss; (7) endocrine disorders (especially resistance to insulin and insulin-like growth factor-I, hyperglucagonemia, hyperparathyroidism and deficiency of 1,25-dihydroxycholecalciferol); (8) products of metabolism that accumulate in renal failure and may induce wasting, such as organic and inorganic acids; (9) loss of the metabolic actions of the kidney; and (10) the accumulation of toxic compounds that are taken up from the environment (e.g., aluminum).
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PMID:Pathophysiology of protein-energy wasting in chronic renal failure. 991 8

There is increasing evidence that androgen therapy in men may be effectively applied in several conditions to improve well being and health. Classical indications for androgen therapy in males are represented by primary or secondary hypogonadism, delayed puberty, aplastic anemia and that secondary to chronic renal failure, protein wasting diseases such as trauma, burns, tumors and infectious diseases. Androgen innovating applications in men are represented by aging and visceral obesity associated with the metabolic syndrome. In addition, it is clear that appropriate testosterone treatment can be adequately used in male contraception, provided spermatogenesis is abolished and tolerability is adequate. Due to unphysiological hormone levels achieved by currently available testosterone preparations, new delivery systems have been produced to achieve more physiological and sustained hormone levels and improve tolerability and action at the levels of target tissues. Some of them are now available in several countries and new formulas are under development.
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PMID:Testosterone therapy in men: clinical and pharmacological perspectives. 1080 80

Substantial losses of total body protein (TBP) can occur in chronic diseases and in aging. Such losses impact negatively on immunity and quality of life, and on growth rates in children. Direct measurements of total body nitrogen (TBN) monitor the integrated changes in TBP over time and allow comparison with normal subjects. TBN assessment via neutron capture analysis is therefore the gold-standard method of TBP estimation, so that risk factors for protein deficit can be identified and patient management optimized. The nitrogen index (NI) can be used to predict prognostic outcome: an NI < 0.9 is associated with substantial wasting in HIV disease, an NI < 0.8 predicts significant pathophysiology in chronic renal failure, and a low NI is predictive of neutropenia in breast-cancer patients. These findings emphasize the central importance of adequate protein stores in recovery from disease or in maintaining quality of life. Aging appears to involve a gradual loss of TBP throughout adulthood. Cross-sectional data suggest that TBP declines curvilinearly with age, such that there is an accelerated decline after 65 years of age. However, longitudinal data are scarce, and little is known about the relative loss of visceral protein, as opposed to skeletal muscle protein. More clearly-defined data are essential if the effects of aging per se are to be separated from the effects of chronic disease. A further complication is the knowledge that physical activity also declines with age. Thus sarcopenia, the loss of skeletal muscle mass, could primarily result from disuse rather than aging. The economic impact of unsuccessful aging places a pressing need for multicompartment data in longitudinal study designs.
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PMID:Total body protein in chronic diseases and in aging. 1086 69

Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Avail-able treatment studies indicate that dietary supplements, either alone or in combination with hormonal treatment, may have positive effects when given to patients with manifest PEM or to patients at risk of developing PEM. In chronic obstructive pulmonary disease, nutritional treatment may improve respiratory function. Nutritional therapy of elderly women after hip fractures may speed up the rehabilitation process. When administered to elderly patients with multiple disorders, diet therapy may improve functional capacity. The data regarding nutritional treatment of the conditions mentioned above is still inconclusive. There is still a great need for randomized controlled long-term studies of the effects of defined nutritional intervention programs in chronically ill and frail elderly with a focus on determining clinically relevant outcomes.
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PMID:Treatment of protein-energy malnutrition in chronic nonmalignant disorders. 1272 Jun 5

Growth in children with chronic renal failure caused by polyuric, salt-wasting diseases may be hampered if ongoing sodium and water losses are not corrected. Twenty-four children were treated with polyuric chronic renal insufficiency (CRI; creatinine clearance <65 ml/min per 1.73 m(2)) with low-caloric-density, high-volume, sodium-supplemented feedings. Subsequent growth was compared with that of children in two control groups: a national historic population control from the US Renal Data System database (n = 42), and a literature control (n = 12). Members of the three groups were 81 to 96% white, and 58 to 70% were boys. Obstructive uropathy and dysplasia were the cause of CRI in 92% of the treatment group, 75% of the literature control group, and 30% of the population control group. Treatment effect was assessed in a multivariate, retrospective analysis of the height standard deviation score (SDS), simultaneously controlling for the severity of disease by renal replacement therapy, primary cause of CRI, and initial height SDS. The change in SDS (Delta SDS) for height by regression analysis at 1 yr was significantly greater by +1.37 in the treatment group versus the population control (P = 0.017). The 2-yr height Delta SDS by regression analysis adjusted for creatinine clearance was significantly greater by +1.83 in the treatment group versus the literature control (P = 0.003). Nutritional support with sodium and water supplementation can maintain or improve the growth of children with polyuric, salt-wasting CRI. This inexpensive intervention may delay the need for renal replacement therapy, growth hormone treatment, or both in many of these children and may be used in any clinical setting.
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PMID:Improved growth in young children with severe chronic renal insufficiency who use specified nutritional therapy. 1196 Oct 34

Pharmacological doses of glucocorticosteroids given chronically are associated with a variety of negative side effects which impact the prolonged use of these potent anti-inflammatory agents. They have catabolic effects on protein, resulting in poor tissue healing, an increased incidence of infections and accelerated bone loss. Insulin resistance to both hepatic and peripheral tissues is a common consequence of chronic steroid use, leading at times to impaired carbohydrate metabolism. Steroids affect both the release and the effects of growth hormone (GH) at the target sites, hence becoming functional GH antagonists. When administered to growing children the side effects of glucocorticosteroid treatment are further compounded by a potent and significant suppression of linear growth. Ample experimental and clinical data support a role for GH therapy in counteracting some of the effects of glucocorticosteroids. Using isotope dilution methods we have previously shown that both GH and insulin-like growth factor (IGF)-I can decrease the protein wasting effects of prednisone administration in man. IGF-I has also been shown to enhance type I collagen formation in hydrocortisone-treated human osteoblasts. GH (through IGF-I) significantly enhances linear growth; thus, in states of "functional" GH deficiency, such as that observed in chronic steroid use, GH may also have a potentially beneficial effect. Studies in children on chronic prednisone doses with cystic fibrosis, chronic renal failure or juvenile rheumatoid arthritis have all shown beneficial effects on linear growth after prolonged GH therapy. Data from a recent study of ours using GH in children with steroid-dependent inflammatory bowel disease showed that GH treatment was associated with increased lean body mass, decreased adiposity and increased linear growth. Marked increases in IGF-I concentrations and in kinetic measures of bone calcium accretion (using calcium tracers) were also observed, without any deterioration of disease activity scores or carbohydrate tolerance. In conclusion, GH therapy may play a role in the treatment of children on chronic steroids both as a growth promoting agent and as an anabolic agent on whole body protein and bone. Longer term studies will be needed to better define the safety and efficacy of this approach.
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PMID:Growth hormone therapy in the glucocorticosteroid-dependent child: metabolic and linear growth effects. 1178 79

Malnutrition and wasting are important determinants of morbidity and mortality in patients with chronic renal failure on dialysis. The aim of this study was to determine body composition and energy metabolism in patients with chronic renal insufficiency before dialysis. We compared 15 patients (9 women and 6 men) with chronic renal failure (creatinine, 1.5 to 4.2 mg/dL) with 15 normal subjects pair-matched for sex, age (renal failure versus normal, 71 +/- 3 years versus 64 +/- 3 years), height (1.61 +/- 0.02 m versus 1.64 +/- 0.02 m), and weight (64.5 +/- 2.7 kg versus 66.4 +/- 1.5 kg). Body composition was measured by dual-energy x-ray absorptiometry, and total body water was measured by bioelectrical impedance. Energy metabolism was determined by indirect calorimetry. The average glomerular filtration rate for the patients with chronic renal insufficiency was 23.9 +/- 2.6 mL/min/1.73 m2. Lean body mass (41.1 +/- 2.0 kg versus 44.5 +/- 2.2 kg; P = 0.003) and bone mineral content (2.35 +/- 0.11 kg versus 2.72 +/- 0.12 kg; P = 0.007) were significantly lower in chronic renal insufficiency; however, fat body mass was the same (19.9 +/- 2.1 kg versus 19.1 +/- 1.4 kg; P = 0.68). Total body water was similar in renal failure (33.4 +/- 1.5 L versus 34.4 +/- 1.3 L; P = 0.13). Basal energy expenditure was significantly lower in chronic renal insufficiency (1,085 +/- 50 kcal/24 hours versus 1,280 +/- 54 kcal/24 hours; P = 0.02), even after adjustment for the differences in lean body mass. Daily caloric intake indicated energy intake was similar in the patients with chronic renal insufficiency and the controls. Patients with a relatively modest degree of chronic renal insufficiency are characterized by reduced lean body mass, bone mineral content, and basal energy expenditure. The determinants of lean body mass in chronic renal insufficiency require further investigation.
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PMID:Body composition and energy metabolism in chronic renal insufficiency. 1184 Mar 87


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