Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic bone disease and growth retardation are common complications of chronic renal failure (CRF). We evaluated bone mineral density (BMD), bone metabolism, body composition and growth in children with CRF, and the effect of growth hormone treatment (GHRx) on these variables. Thirty-three prepubertal patients with CRF were enrolled including 18 children with growth retardation, who were treated with growth hormone for 2 years. Every 6 months, BMD of lumbar spine and total body, and body composition were measured by dual-energy X-ray absorptiometry. Biochemical parameters of bone turnover were assessed. Mean BMD of children with CRF did not differ from normal. During GHRx, BMD and bone mineral apparent density of lumbar spine and height SDS increased, whereas BMD of total body did not change. Lean body mass increased in the GH group. Alkaline phosphatase increased significantly in the GH group only. The other biochemical parameters of bone turnover increased in both groups, none of them correlated with the changes in BMD. No serious adverse effects of GHRx were reported. In conclusion, BMD of children with CRF did not differ from healthy children. Adequate treatment with alpha-calcidiol or the short duration of renal failure may have attributed to the absence of osteopenia in our patients. BMD of the axial skeleton and growth improved with GHRx.
 ...
PMID:Bone density and body composition in chronic renal failure: effects of growth hormone treatment. 1114 15

Wasting disease states can be characterized either by decreased or accelerated protein turnover. Slow protein turnover conditions include some chronic disease states characterized by low protein-energy intake, immobilization, tissue hypoxia, or moderate liver or kidney failure. Rapid protein turnover conditions include the acute hypercatabolic states and some chronic disease characterized by systemic inflammation. Anabolic hormones, such as growth hormone and androgenic steroids, act by stimulating protein turnover especially in skeletal muscle. These therapies appear to be safe and efficacious in chronic diseases states where they tend to increase and normalize a rate of protein turnover which is already depressed. In critically ill patients with a preexisting condition of accelerated protein turnover, it might therefore not be appropriate to further accelerate the rate of protein turnover by using these anabolic agents. Chronically uremic patients often exhibit a low protein turnover that may increase progressively with the decline of renal function. Thus, anabolic agents can normalize protein metabolism in stable patients without complications, but they should be used carefully in advanced renal failure especially during intercurrent infections.
 ...
PMID:Can we increase protein synthesis by anabolic factors? 1115 75

Chronic renal failure in childhood causes severe growth retardation. The aim of the study was to identify whether changes in the IGF system could account for the growth retardation observed in children with chronic renal failure. Insulin-like growth factor (IGF-I) serum concentrations, insulin-like growth factor binding proteins (IGFBP) and/or IGF-I binding to erythrocyte type I receptor of IGF were analysed in 69 children (mean age 11.6 +/- 4.3 years) with chronic renal failure and growth retardation (mean height -2.6 +/- 1.8 SD). The study population was separated into three groups, according to their renal status, children on conservative treatment (CRF group: n = 30), on haemodialysis (ESRD group: n = 26) and those transplanted (RT group: n = 13). Nineteen of these children, some from each of the three groups, received recombinant growth hormone therapy (rhGH). Mean basal IGF-I serum concentrations were -0.7 +/- 1.2 SD in the CRF group, + 2.1 +/- 3 SD in the ESRD group and + 1.1 +/- 2 SD in the RT group. Under rhGH therapy, as height velocity improved, mean IGF-I concentrations increased up to + 3.1 +/- 0.6 SD in the CRF group, to + 6.9 +/- 2.8 SD in the ESRD group and to + 3.9 +/- 2 SD in the RT group. Basal IGFBP-3 levels, studied by Western Ligand Blot were low in the CRF group and high in the ESRD and normal in the RT groups, whereas IGFBP-2 and a 30-32 kDa IGFBP were always high in all cases. Western immunoblot analysis showed that this 30-32 kDa IGFBP was mostly composed of IGFBP-1 and IGFBP-6 in all three groups, but IGFBP-6 was particularly abundant in the ESRD group. IGFBP-6 concentrations assessed by RIA were moderately increased in CRF children (392 +/- 177 ng/mL) and very high in children on ESRD (2094 +/- 1525 ng/mL) when compared to normal values (131 +/- 42 ng/mL). Binding studies of IGF type I receptor showed that there was no particular difference in IGF-I binding between renal failure patients and normal children. In poorly growing children, especially in ESRD children and to a lesser extent in RT children, high concentrations of IGF-I and IGFBP-1, 2, 3 and 6, suggest a resistance mainly by a sequestration mechanism. Moreover, in the CRF group, especially in the younger children, low levels of IGF-I and IGFBP-3 are evocative of an associated resistance at the GH receptor level.
 ...
PMID:Insulin-like growth factor-I (IGF-I), insulin-like growth factor binding proteins (IGFBP) and insulin-like growth factor type I receptor in children with various status of chronic renal failure. 1116 64

The long-term effects of growth hormone (GH) administration are unknown. Although limited data on its short-term effects purport health benefits, numerous detrimental effects are the consequence of chronically elevated GH. We used spectrophotometric assay and Western blot to determine the effects of chronic GH excess on hepatic and renal antioxidant enzymes (AOEs) in young and middle-aged PEPCK (phosphoenolpyruvate carboxykinase) hGH (human GH) transgenic mice. In the liver, glutathione peroxidase (GPx) was reduced in transgenics of both age groups, catalase was reduced only in young transgenics, and Cu-Zn superoxide dismutase (SOD) was similar to normal mice, but declined with age. In all groups, hepatic AOE activity correlated significantly with AOE level. In the kidney, AOEs in young transgenics were similar to those of normal mice. However, middle-aged transgenics showed reduced renal SOD and GPx activities when compared with young transgenic or middle-aged normal mice. Similarly, renal SOD and GPx levels in middle-aged transgenics were reduced when compared with those of middle-aged normal mice. AOE activity in the kidney correlated significantly with AOE protein level among middle-aged animals only. These data suggest the following: ((1)) GH excess is associated with early declines in SOD and GPx in the kidney and reductions of hepatic GPx at all ages examined, perhaps increasing the risk of free radical-induced damage to these tissues; ((2)) in the liver of young animals and in the liver and kidney of middle-aged animals, AOE activity reflects the amount of enzyme protein; and ((3)) age-related reductions in GPx in transgenics may be related to the increased incidence of liver tumors and renal failure in these animals.
 ...
PMID:Free radical defenses in the liver and kidney of human growth hormone transgenic mice: possible mechanisms of early mortality. 1128 86

The present state of knowledge about growth hormone binding proteins (GHBP) is reviewed, with particular emphasis on the high affinity GHBP, which represents the circulating ectodomain of the growth hormone receptor (GHR). GHBP is conserved through vertebrate evolution, is produced in many tissues (especially liver) by either alternative GHR mRNA splicing (rodents) or by proteolytic cleavage from the GHR (humans, rabbits and several other species). The metalloprotease TACE (tumor necrosis factor-alpha converting enzyme) is the likely enzyme responsible for cleavage, but the structural requirements for TACE recognition or catalysis, and hence the precise cleavage point in the GHR, are unknown. GHBP is widely distributed in biological fluids, with marked concentration differences amongst them. GHBP binds about half of the circulating GH under basal conditions but is easily saturated at high GH levels; it subserves complex functions, including a circulating buffer/reservoir function for GH, prolongation of plasma GH half-life, competition with GHRs for GH, and probably unproductive heterodimer formation with the GHR. The net effect of these partly enhancing and partly inhibitory functions on GH action in vivo is complex and difficult to ascertain. Serum GHBP levels roughly parallel GHR expression (particularly in liver) through the life span, with very low levels in fetal life, upregulation to adult levels during childhood, and decline in senescence. Rodent pregnancy is associated with a massive increase in GHBP expression. Although the regulation of GHBP expression/production is not necessarily tightly linked to GHR expression, in general, low GHBP levels occur in conditions associated with GH resistance (e.g., malnutrition, uncontrolled diabetes, catabolic states, renal failure, hypothyroidism). Conversely, obesity, a condition with enhanced GH responsivity, is associated with elevated GHBP levels. This suggests that in many (but not all) instances of abnormal GH action, the GHBP level reflects GHR status. Laron syndrome (genetic GHR deficiency/dysfunction due to mutations in the GHR gene) is associated with low or undetectable GHBP in 75-80% of patients; GHBP measurement can therefore be used diagnostically. Depending on the design of assays for serum GH, endogenous GHBP may interfere to varying degrees, and GH assays should be individually validated and optimized in this regard. The ultimate biological role and physiological significance of the GHBP remain to be established.
 ...
PMID:Growth hormone binding protein 2001. 1132 70

The diagnosis of chronic renal insufficiency (CRI) must be evoked in children with feeding difficulties, excessive thirst, insufficient weight and/or height gain. Complications of CRI in children are hydroelectrolytic desequilibrium (chronic dehydration, sodium depletion, acidosis), nutritional difficulties, osteodystrophy, growth retardation and psychologic and scolar difficulties. Human recombinant growth hormone treatment generally allows spectacular growth improvement. In children with end-stage renal failure, operation is performed by hemodialysis or, especially in children less than 2 years of age, peritoneal dialysis. Renal transplantation is the best treatment of end-stage renal failure in children, as it offers them a practically normal life, with the only obligation of absorbing medications every day.
 ...
PMID:[Chronic renal insufficiency in children]. 1135 6

Renal failure is associated with dramatic changes in the growth hormone/insulin-like growth factor (GH/IGF) axis. In children, this results in growth retardation, which is treated with injections of recombinant human GH (rhGH). Given the many recent advances in the knowledge of the components of the GH/IGF axis, it is timely to review the role of GH in renal failure and to discuss likely new treatments for growth failure. Renal failure is not a state of GH deficiency but a state of GH and IGF resistance, making other approaches to manipulating the GH axis more logical than treatment with rhGH alone. Although in children rhGH is safe, in critically ill adults it can be lethal. As the mechanisms of these lethal actions of rhGH are unknown, caution is advised when using rhGH outside approved indications. In renal failure, an optimal balance between safety and efficacy for growth may be achieved with the use of the combination of rhGH and rhIGF-I, as animal studies have shown synergistic growth responses. However, inhibition of the GH axis, with the use of GH antagonists, is likely to be tested clinically given the beneficial effects of GH antagonists on renal function in animal models of renal disease. Manipulating IGF-I by either administering rhIGF-1 or its binding proteins or increasing IGF-I bioavailability with the use of IGF displacers could prove to be a safer and more effective alternative to the use of rhGH in renal failure. In the future, both rhGH and rhIGF-1 likely will be included in growth-promoting hormone cocktails tailored to correct specific growth disorders.
 ...
PMID:The growth hormone and insulin-like growth factor axis: its manipulation for the benefit of growth disorders in renal failure. 1137 55

Advanced chronic renal failure is associated with multiple endocrine and metabolic abnormalities that result from changes in the secretion and metabolism of hormones and growth factors and the target organ sensitivity to their physiological actions. As a consequence, growth retardation, bone disease, pertubations in lipid, carbohydrate and protein metabolism are commonly seen in patients with chronic renal failure. The recent availability of recombinant growth factors has provided new therapeutic opportunities for correcting these abnormalities. However because of the presence of end-organ resistance relatively high dose therapy is required and this carries an increased risk of side effects. One logical approach to this problem would be to prevent or treat the underlying resistance and thus restore sensitivity to endogenous GH or low doses of the recombinant molecule. To achieve this goal, a better understanding of the mechanism of growth factor resistance is required. In this lecture, in honor of the memory of Frank Carone. I review our current state of knowledge of the impact of advanced renal failure on the tissue sensitivity to insulin, growth hormone and insulin-like-growth factor I.
 ...
PMID:Growth factor insensitivity in renal failure. 1149 45

In agreement with recent studies showing a deleterious effect of growth hormone treatment in critically ill patients, preliminary data showed that insulin-like growth factor I (IGF-I) administration increased the mortality rate of rats with ischemic acute renal failure (ARF). The present study was designed to investigate the mechanism responsible for this unexpected effect. Male rats with ischemic ARF were given subcutaneous IGF-I, 50 microg/100 g at 0, 8, and 16 h after reperfusion (ARF+IGF-I, n = 5) or were untreated (ARF, n = 5). A group of 5 sham-operated rats were used as controls. Rats were killed 48 h after declamping, and the following studies were performed: in serum, creatinine and urea nitrogen; and in kidneys, histologic damage score, cellular proliferation by bromodeoxyuridine labeling, apoptosis by morphologic criteria, macrophage infiltration by immunohistochemistry using a specific antibody against ED-1, neutrophil infiltration by naphthol AS-D chloroacetate esterase staining, and levels of IGF-I and IGF-I receptor mRNA by RNase protection assay. ARF and ARF+IGF-I groups had a severe and similar degree of renal failure. Kidney damage was histologically more evident in ARF+IGF-I (1.9 +/- 0.1) than in ARF (1.3 +/- 0.2) rats, and the number of neutrophils/mm(2) of tissue was significantly greater in ARF+IGF-I than in ARF rats at the corticomedullary junction (52.3 +/- 5.2 versus 37.2 +/- 4.1) as well as at the renal medulla (172.5 +/- 30.0 versus 42.1 +/- 9.6). No other differences between the groups were found. It is concluded that IGF-I treatment enhanced the inflammatory response in rats with ischemic ARF. Cell toxicity derived from increased neutrophil accumulation might play a key role in the greater mortality risk of critically ill patients that are treated with growth hormone.
 ...
PMID:Exacerbated inflammatory response induced by insulin-like growth factor I treatment in rats with ischemic acute renal failure. 1151 83

The wider availability of recombinant human growth hormone and insulin-like growth factor-I has resulted in an investigation into the potential benefits of the pharmacological administration of these anabolic peptides in a variety of clinical conditions, characterized by an increase in catabolic rate. The initial studies were small, often uncontrolled open investigations, but investigators have more recently concentrated on larger, controlled multi-centre trials. Studies to date have included patients with cardiac failure, sepsis, burns, cancer cachexia, end-stage renal failure, trauma and AIDS, and those prior to or following major surgery. The authors have in general cautiously interpreted positive effects of treatment with growth hormone and insulin-like growth factor-I, either alone or in combination, on net protein balance, body composition, well-being and performance. Two large, randomized, placebo-controlled European multi-centre studies have recently detailed the effects of growth hormone treatment in critically ill intensive care patients. Major increases in mortality and morbidity were associated with growth hormone treatment. The mechanism(s) accounting for the increased mortality remain poorly understood. These negative findings have led to a decrease in the clinical use of growth hormone and in research activity in the area of anabolic treatment in human illness.
 ...
PMID:Treatment with growth hormone and insulin-like growth factor-I in critical illness. 1180 May 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>