Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0240066 (iron deficiency)
 7,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The target organ failures associated with uremia are most often considered to be caused by processes other than uremia per se. Heart disease, for example, is considered the product of hypertension, lipid abnormalities, and so forth, rather then the uremic state. Erythropoietin deficiency, blood loss, and iron deficiency are believed to cause anemia, rather than the uremic state. Malnutrition is believed to be the product of poor nutrient intake and perhaps nutrient losses, rather than uremia per se. This article reviews evidence suggesting that anemia and malnutrition share a common cause; the acute-phase inflammatory process that is a normal host-defense mechanism. Given the high prevalence of heart disease among patients with end-stage renal disease (ESRD), data indicating activation of the acute-phase process in patients with kidney failure, and emerging evidence that the process has a significant role in the risk for cardiovascular disease among patients without kidney failure, there is a strong likelihood that heart disease will share with anemia and malnutrition the acute-phase state as a contributing cause. Thus, instead of disconnected target organ failures, each with different antecedent causes, we see emerging the likelihood of a unifying pathobiology for uremia. The antecedents of morbidity and mortality appear as a web of organ failures connected by a common pathobiology. Whereas each failure likely has contributing causes other than the acute-phase state, they probably share the state as a causative, contributing, or exacerbating factor.
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PMID:Acute-phase inflammatory process contributes to malnutrition, anemia, and possibly other abnormalities in dialysis patients. 989 76

In most chronic disease conditions, the systemic inflammatory response and its mediators play an essential pathogenic role. Protein calorie malnutrition, a prominent feature of end-stage renal disease (ESRD), also develops, largely as a consequence of the systemic inflammatory response. ESRD (uremia), dialysis, systemic metabolic acidosis, and infections activate the systemic inflammatory response. Elevations in C-reactive protein and depressions of serum albumin below 4 g/dL are found in more than 50% of ESRD patients undergoing dialysis. In many patients receiving dialysis, the impact of this acute-phase response on measures of iron metabolism limits the ability to diagnose iron deficiency. Furthermore, there are risks to iron administration, although data linking iron overload to risk of infection in dialysis patients is suggestive, not definitive. It seems reasonable to hypothesize that the greatest risk of iron administration is in patents who are already infected, and the greater risk would be to raise the serum iron level and transferrin saturation precipitously. The total-dose infusion method, which provides all iron required to correct deficiency in 1 dose, is more likely to produce side effects and rapidly raise serum iron levels and transferrin saturation. The use of low-dose intravenous iron supplementation (10 to 20 mg per dialysis treatment or 100 mg every second week) avoids iron overtreatment and should reduce adverse events. In ESRD patients receiving dialysis, the importance of the systemic inflammatory response in the development of protein calorie malnutrition, the impact of the acute-phase response on iron nutriture, and the response to erythropoietin therapy must be considered to achieve an understanding of the altered responses to nutritional therapy in this setting.
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PMID:The systemic inflammatory response and its impact on iron nutriture in end-stage renal disease. 1051 74

Restless legs syndrome (RLS) is a neurologic movement disorder that is often associated with a sleep complaint. Patients with RLS have an irresistible urge to move their legs, which is usually due to disagreeable sensations that are worse during periods of inactivity and often interfere with sleep. It is estimated that between 2 and 15 percent of the population may experience symptoms of RLS. Primary RLS likely has a genetic origin. Secondary causes of RLS include iron deficiency, neurologic lesions, pregnancy and uremia. RLS also may occur secondarily to the use of certain medications. The diagnosis of RLS is based primarily on the patient's history. A list of questions that may be used as a basis to assess the likelihood of RLS is included in this article. Pharmacologic treatment of RLS includes dopaminergic agents, opioids, benzodiazepines and anticonvulsants. The primary care physician plays a central role in the diagnosis and management of RLS.
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PMID:Restless legs syndrome: detection and management in primary care. National Heart, Lung, and Blood Institute Working Group on Restless Legs Syndrome. 1127 42

Periodic limb movement disorder (PLMD) is one of the commonest neurological disorders and causes significant disability, if left untreated. However, it is rarely diagnosed in clinical practice, probably due to lack of awareness and/or lack of necessary diagnostic facilities. Restless leg syndrome (RLS), aging, pregnancy, uraemia, iron deficiency, polyneuropathy are some of the common causes of secondary PLMD. Clinical presentation, polysomnographic findings and management of six patients of PLMD have been discussed in this report.
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PMID:Periodic limb movement disorder : a clinical and polysomnographic study. 1179 9

Patients receiving epoetin therapy show wide variability in their responsiveness to the drug. Many factors may be responsible for this, particularly iron deficiency, acute infection and under-dialysis. Even after excluding factors known to cause resistance to epoetin, the marked variability in sensitivity to epoetin remains. The exact mechanism of this effect is unclear. It is, however, recognized that uraemia is a chronic inflammatory state, with some patients showing quite significantly increased laboratory markers of inflammation and immune activation. It is also known that chronic inflammation can modify the process of erythropoiesis, and this is probably mediated via pro-inflammatory cytokines such as interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). It is hypothesized, therefore, that some patients showing resistance to epoetin may have enhanced levels of immune activation, causing increased release of pro-inflammatory cytokines in the bone marrow. This has been investigated by studying T-cell phenotypes by flow cytometry, along with cytokine release from T cells and monocytes in 'good' and 'poor' responders to epoetin. Poor responders were found to have significantly reduced CD28 expression on both CD4(+) and CD8(+) cells, enhanced IL-10 generation from peripheral blood mononuclear cells (PBMCs), higher plasma IL-12 levels and enhanced TNF-alpha release from PBMCs. The patients in this study, who were followed-up for the subsequent 24 months, had a considerably lower survival if they were poor responders (54% vs 88% for good responders; P<0.05). Further work in this area is required to confirm or contest the hypothesis that epoetin resistance is due to enhanced levels of immune activation.
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PMID:The inflammatory response and epoetin sensitivity. 1181 13

Up to 10% of patients with renal disease receiving recombinant human erythropoietin (rHuEPO) therapy show poor responsiveness to the drug. Even in patients who do respond to rHuEPO, there is a marked variability in drug sensitivity. Several factors have been recognized as causing resistance to rHuEPO, notably iron deficiency, infection/inflammation, and under dialysis. However, when these factors are excluded, the wide variation in responsiveness to rHuEPO persists. The mechanism of this effect needs to be fully elucidated. One hypothesis is that patients with uraemia showing resistance to rHuEPO may have enhanced levels of immune activation, causing increased release of pro-inflammatory cytokines in the bone marrow. Uraemia is known to be a chronic inflammatory state, with some patients showing considerably increased laboratory markers of inflammation and immune activation. Chronic inflammation can modify the process of erythropoiesis, probably mediated via pro-inflammatory cytokines such as interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The concept that rHuEPO resistance is due to enhanced levels of immune activity has been investigated by studying T-cell phenotypes using flow cytometry, as well as cytokine release from T cells and monocytes in 'good' and 'poor' responders to rHuEPO. Poor responders had significantly reduced CD28 expression on both CD4+ and CD8+ cells, enhanced IL-10 generation from peripheral blood mononuclear cells (PBMCs), higher plasma IL-12 levels, and increased TNF-alpha and IFN-gamma release from PBMCs. Anti-cytokine antibodies may be useful for studying inflammatory cytokine secretion from T cells in patients with renal failure. Strategies utilizing anti-cytokine therapy may prove to be a useful adjuvant in optimizing the response to rHuEPO therapy.
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PMID:Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. 1238 57

Restless legs syndrome (RLS) is common in the elderly, with an estimated prevalence of 10 to 35% in individuals over 65 years of age. RLS is characterised by paraesthesias and dysaesthesias of the legs, typically occurring in the evening. The symptoms occur at rest and result in motor restlessness; movement often temporarily relieves the symptoms. Patients with poorly controlled RLS may develop related problems including insomnia (due to sleep-onset restlessness or periodic limb movements or related sleep fragmentation) and depression. RLS can be a primary disorder that develops in the young and includes familial cases. Secondary RLS occurs in association with iron-deficiency anaemia, uraemia and polyneuropathies. Typically, RLS is misdiagnosed or undiagnosed for years. In the elderly, both primary and secondary types of the disorder are common. It is thought that RLS represents lower CNS levels of, or reduced responsiveness to, dopamine. The symptoms improve with dopaminergic therapy. Ergotamine dopamine-receptor agonists such as pergolide, and the non-ergotamine dopamine-receptor agonists pramipexole and ropinirole, are becoming more commonly used to treat RLS. The dopamine precursor levodopa, in combination with carbidopa, is another effective therapeutic agent. An advantage of levodopa is lower cost than non-ergotamine and ergotamine dopamine-receptor agonists. However, the adverse effect of symptom augmentation appears to develop more frequently with levodopa than dopamine-receptor agonists; therefore, levodopa may currently be used somewhat less often as first-line therapy. Patients with painful symptoms may respond favourably to the anticonvulsants gabapentin and carbamazepine. Opioids and hypnosedatives are helpful in selected patients; however, these agents may have troubling adverse effects in the elderly. Correction of iron deficiency improves symptoms in patients with low ferritin levels. Lifestyle modification may also be helpful. Therapy is directed at symptoms, and most symptomatic patients benefit from treatment. It is important to consider RLS in the differential diagnosis of any patient with paraesthesias of the limbs.
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PMID:Restless legs syndrome in the older adult: diagnosis and management. 1239 51

The past decade has seen an explosion of interest in both idiopathic and secondary restless legs syndrome (RLS). Secondary RLS occurs in patients with uremia, pregnancy, and iron deficiency. Patients experience an irresistible urge to move the legs that is worse during inactivity and at night. RLS affects 6.6% to 62% of patients on long-term dialysis therapy and is associated with a greater mortality risk. The wide range of reported prevalence is explained in part by variations in methods of diagnosis. The International Restless Legs Syndrome Study Group defined diagnostic criteria that have improved the quality of RLS research. Advanced neurological imaging techniques suggest the pathophysiological state of idiopathic RLS involves dysfunction of subcortical areas of the brain. Dopaminergic pathways and neuronal iron handling have been implicated. Limited studies of patients with uremic RLS suggested similar mechanisms, but anemia, hyperphosphatemia, and psychological factors also may have a role. The few clinical trials in uremic RLS suggest that treatment should involve the reduction of potential exacerbating agents (tricyclic antidepressants, selective serotonin uptake inhibitors, lithium, and dopamine antagonists), correction of anemia (with erythropoietin and iron), and use of levodopa or dopamine agonists. Other agents shown to be of benefit in idiopathic RLS can be tried, but may be limited by side effects in patients with uremia (benzodiazepines, opioids, gabapentin, carbamazepine, and clonidine). Symptoms of uremic RLS will disappear within a few weeks of successful renal transplantation. The progress made to date in unraveling the pathophysiological state of uremic RLS should stimulate additional research toward targeted therapy.
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PMID:Restless legs syndrome in patients on dialysis. 1511 66

Restless legs syndrome (RLS) is a sensory-motor disorder characterized by discomfort of and urge to move the legs, primarily during rest or inactivity, partial or total relief with movement, with presence or worsening exclusively in the evening. It is a relatively common but frequently unrecognized disorder, with a prevalence ranging from 2.5 to 15% of the general population, increasing with age and with a female preponderance. The diagnosis is clinical but polysomnography is useful to determine its profound impact on sleep (difficulties in sleep onset, maintaining sleep during the night, and sleep fragmentation) and for the evidence of periodic legs movements during sleep and wake. RLS is generally idiopathic, with familial association in 40-60% of the cases, but may also be symptomatic of such associated conditions (secondary forms) as peripheral neuropathies, uremia, iron deficiency (with or without anemia), diabetes, Parkinson's disease and pregnancy. Response to dopaminergic drugs indicates that dopamine receptors are implicated, and although much progress has been made in diagnosis and treatment in the last decade, more is needed for complete elucidation of the etiology and pathophysiology of RLS.
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PMID:Epidemiology and clinical findings of restless legs syndrome. 1516 38

Restless legs syndrome (RLS) is a poorly understood sleep-related movement disorder which can be primary or associated with other conditions, most commonly iron deficiency, uremia and peripheral nerve disease. We present a case of RLS with an unusual secondary cause: primary hyperparathyroidism with hypercalcemia. This patient experienced complete and sustained relief of RLS symptoms immediately after parathyroidectomy, with normalization of her serum parathyroid hormone (PTH) and calcium levels. Early recognition and treatment of this uncommonly detected underlying cause is important because it is potentially curative in this frequently disabling condition for which usually only symptomatic treatment is available.
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PMID:Restless legs syndrome associated with primary hyperparathyroidism. 1585 61


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