Gene/Protein Disease Symptom Drug Enzyme Compound
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 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Appropriate initiation of dialysis is of an outstanding importance in the treatment of patients with end-stage renal disease. It prevents development of irreversible uremic complication and enables selection of the most appropriate dialysis modality for the individual patient. The major causes of morbidity and mortality in dialysis patients are cardiovascular diseases. Hypertension and hyperlipidemia are commonly found in dialysis patients as well as anemia, chronic inflammation and fluid overload, all of which are found to be risk factors for the development of cardiovascular diseases. Arterial hypertension is the main risk factor for left ventricular hypertrophy, and there is clear evidence that control of hypertension has a beneficial effect on left ventricular hypertrophy. It is best achieved by correction of overhydration and maintenance of dry weight. Modern dialysis machines are capable of changing electrolyte concentrations, which reduces intradialytic cardiovascular complications, incidence of cardiac arrhythmias and hypotension. Correction of anemia with erythropoietin results in regression of left ventricular hypertrophy and improvement of the quality of life and defense against microorganisms. Chronic inflammation can be prevented with the use of biocompatible high-flux dialysis membranes and sterile dialysate, which are also important for the prevention of oxidative stress involved in the increase of LDL oxygenation and incorporation into the intimal layer of the vessels. Low molecular weight heparins by their action on lipoprotein lipase serve as an additional factor that suppresses development of atherosclerotic plaque in dialysis patients. Optimal dialysis dose decreases the mortality and morbidity rates. High-flux membranes or prolongation of dialysis session are modalities for dialysis dose improvement. Individualized approach to preparation of dialysis solutions has resulted in better control of fluid overload and intradialytic hyper- or hypotension, reduction in the incidence of arrhythmias, improvement of hemodynamic stability, and delay of renal osteodystrophy. Malnutrition is a relatively common problem in dialysis patients that may be secondary to poor nutritional intake, inadequate amount of dialysis, lack of appetite, acidosis, associated disease, and/or increase in protein catabolism. The most appropriate approach includes individualization of dietary prescription according to the nutritionist's advice, increase of dialysis dose with biocompatible membranes, and use of sterile bicarbonate dialysate with glucose and erythropoietin. The major goal of adequate dialysis is not just improvement in survival of dialysis patients, but also improvement in the quality of their lives.
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PMID:[Biological adequacy--what does it mean?]. 1512 86

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.
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PMID:Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy. 1515 77

(1) Existing treatments for cutaneous T cell lymphoma (topical agents, chemotherapy, photopheresis, interferon alfa) have cosmetic benefits but no impact on survival. (2) Bexarotene, a synthetic retinoid, is approved for the treatment of adults with advanced-stage cutaneous lymphoma refractory to at least one systemic treatment. (3) Two non comparative trials included patients who were refractory or in relapse after various systemic treatments: one included 58 patients at an early stage of the disease, and the other 94 patients at an advanced stage. The evidence from these trials is weak for several reasons such as the lack of a standard endpoint for efficacy and numerous protocol modifications. The optimal dose of bexarotene is unknown. No comparative trials are available, and indirect comparisons are often misleading. (4) Nearly all patients treated with bexarotene suffer adverse effects, which can include hyperlipidemia (risk of pancreatitis), hypothyroidism, and haematological reactions (leukopenia, anemia). There is also an unconfirmed risk of cataract. (5) In practice, bexarotene is a highly toxic drug with uncertain efficacy, and there is no reason to prescribe it. Bexarotene should never have been authorised on the basis of such a bad evaluation.
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PMID:Bexarotene: new preparation. Cutaneous lymphoma: too many adverse effects. 1523 46

About 1,000 children develop end-stage renal disease (ESRD) each year in the United States and about 5,000 children are currently receiving dialysis. Children who develop ESRD are eligible to receive renal replacement therapy, including renal transplantation. There are inherent risks associated with transplantation, including renal insufficiency, infections, post-transplant lymphoproliferative disorder, and cardiovascular disease (CVD). Potential risk factors for CVD in pediatric renal transplant recipients include renal insufficiency, hyperlipidemia, hyperhomocysteinemia, inflammation, malnutrition, anemia, and hyperglycemia/insulin resistance. Despite evidence that many children may possess various risk factors for CVD post-renal transplantation, there are very few studies that have attempted to assess the link between these risk factors and CVD in pediatric renal transplant recipients.
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PMID:Risk factors for cardiovascular disease in pediatric renal transplant recipients. 1526 67

In the control of acute rejection, attention is being focused more and more on the long-term adverse effects of the immunosuppressive agents used. Since cardiovascular disease is the main cause of death in renal transplant recipients, optimal control of cardiovascular risk factors is essential in the long-term management of these patients. Unfortunately, several commonly used immunosuppressive drugs interfere with the cardiovascular system. In this review, the cardiovascular adverse effects of the immunosuppressive agents currently used for maintenance immunosuppression are thoroughly discussed. Optimising immunosuppression means finding a balance between efficacy and safety. Corticosteroids induce endothelial dysfunction, hypertension, hyperlipidaemia and diabetes mellitus, and impair fibrinolysis. The use of corticosteroids in transplant recipients is undesirable, not only because of their cardiovascular effects, but also because they induce such adverse effects as osteoporosis, obesity, and atrophy of the skin and vessel wall. Calcineurin inhibitors are the most powerful agents for maintenance immunosuppression. The calcineurin inhibitor ciclosporin (cyclosporine) not only induces these same adverse effects as corticosteroids but is also nephrotoxic. Tacrolimus has a more favourable cardiovascular risk profile than ciclosporin and is also less nephrotoxic. It has little or no effect on blood pressure and serum lipids; however, its diabetogenic effect is more prominent in the period immediately following transplantation, although at maintenance dosages, the diabetogenic effect appears to be comparable to that of ciclosporin. The diabetogenic effect of tacrolimus can be managed by reducing the dose of tacrolimus and early corticosteroid withdrawal. The effect of tacrolimus on endothelial function has not been completely elucidated. The proliferation inhibitors azathioprine and mycophenolate mofetil (MMF) have little effect on the cardiovascular system. Yet, indirectly, by inducing anaemia, they may lead to left ventricular hypertrophy. MMF is an attractive alternative to azathioprine because of its higher potency and possibly lower risk of malignancies. Sirolimus also induces anaemia, but may be promising because of its antiproliferative features. Whether the hyperlipidaemia induced by sirolimus counteracts its beneficial effects is, as yet, unknown. It may be combined with MMF, however, initial attempts resulted in severe mouth ulcers.
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PMID:Effect of immunosuppressive agents on long-term survival of renal transplant recipients: focus on the cardiovascular risk. 1534 97

Chronic allograft nephropathy (CAN) is the most common cause of late renal transplant loss. Calcineurin inhibitor (CNI) nephrotoxicity is known to contribute to CAN. A sirolimus-based regimen way allow for early CNI reduction or elimination. The aim of the present study was to determine the efficacy and safety of a sirolimus-based regimen for CAN. From December 2001 to August 2003, kidney transplant (KTx) recipients with CAN were enrolled for treatment with sirolimus. Among 32 studied patients, 24 (75%) underwent graft biopsy before the initiation of sirolimus. Baseline maintenance immunosuppression consisted of cyclosporine/tacrolimus and prednisone with or without mycophenolate mofetil. The follow-up duration on sirolimus therapy was 8.5 +/- 5.9 months (range: 1 to 22 months). The average dosage of sirolimus was 1.8 +/- 0.5 mg/d at the end of follow-up. The mean trough level of sirolimus was 5.1 +/- 2.1 ng/mL. Sirolimus was effective in 16 (50%) patients while 3 (9.4%) patients improved (serum creatinine [Cr] decrease > 10%) and 13 (40.6%) maintained stable (change of serum Cr within 10%). Sirolimus was effective in 5 (35.7%) patients whose serum Cr was over 3.0 mg/dL but failed to rescue all four patients whose serum Cr was over 4.0 mg/dL. Eleven (68.8%) of 16 responders showed a reduction (29.8% +/- 13.8%) in CNI dosage. The most common adverse events were hyperlipidemia (37.5%), anemia (25%), and diarrhea (21.8%). Twelve patients discontinued sirolimus due to graft failure (4), severe infection (3), stroke related mortality (1), anemia (2), diarrhea (1), and edema (1). In conclusion, sirolimus is effective in 50% of KTx recipients with CAN, especially when the serum Cr is less than 3.0 mg/dL. However, the increased incidence of infection, diarrhea, and hyperlipidemia are of major concern.
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PMID:Sirolimus in chronic allograft nephropathy. 1551 43

This pilot study was designed to evaluate the safety and efficacy of converting from a calcineurin inhibitor (CI) to a sirolimus (SRL)-based regimen in established renal transplant recipients with moderate renal insufficiency. Sixty renal transplant recipients on CI-based immuno-suppression with a serum creatinine (SCr) between 159 and 265 microM (1.8 and 3.0 mg/dL) and a glomerular filtration rate (GFR) between 30 and 70 mL/min were enrolled. SRL dosing was dependent upon concomitant immunosuppressive therapy. The mean patient age was 45 yr and the mean time from transplant to study enrollment was 60.8 months (range: 7-198). The median SCr was 168 microM (1.9 mg/dL) and the median GFR was 51 mL/min. Twelve months after conversion the patient and graft survival rates were 96.7% and 95%, respectively. The incidence of biopsy-proven acute rejection was 3.3% (two cases reported, Banff grades IA and IB). The median SCr and median creatinine clearance were 168 microM (1.9 mg/dL) and 53 mL/min, respectively. Hyperlipidemia, diarrhea, peripheral edema, rash, and anemia were the most commonly reported adverse events. Patients with moderate renal insufficiency can be converted from CI to SRL-based therapy and maintain renal function over a 1-yr period.
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PMID:An open-label, pilot study evaluating the safety and efficacy of converting from calcineurin inhibitors to sirolimus in established renal allograft recipients with moderate renal insufficiency. 1565 46

Highly active antiretroviral therapy (HAART) has changed the natural history of HIV infection, but the presence of adverse events may limit its efficacy. Nucleoside reverse transcriptase inhibitors can cause mitochondrial toxicity and anemia, non-nucleoside reverse transcriptase inhibitors are associated with rash and central nervous system disturbance; protease inhibitors elicit gastrointestinal adverse effects and metabolic abnormalities including lipodystrophy syndrome, hyperlipidemia and insulin resistance. These complications have the potential to increase morbidity and mortality significantly in those requiring long-term treatment of HIV-infection. The presence of such abnormalities also has an impact on adherence to treatment. Besides providing health benefits, HAART may have a negative impact on patients' quality of life. Identifying and treating these complications has important implications for patient survival.
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PMID:[Side effects of antiretroviral therapy]. 1568 51

Cardiac disease is the leading cause of death in patients having end-stage renal disease (ESRD). Patients with ESRD have a higher risk for developing coronary artery disease (CAD) than one would estimate from the presence of traditional risk factors such as hypertension, diabetes, hyperlipidemia, and cigarette smoking. Patients with milder forms of renal dysfunction who do not require dialysis also appear to have an increased risk for CAD. ESRD is associated with anemia, hyperhomocystinemia, increased calcium-phosphate product, hypoalbuminemia, increased troponin, increased markers of inflammation, increased oxidant stress, and decreased nitric oxide activity, factors that could contribute to increased CAD risk. Patients with ESRD require aggressive management of traditional risk factors for CAD, which include hypertension, hyperlipidemia, hyperhomocystinemia, and hypercoagulability. Milder forms of renal dysfunction could also be predictors of occult CAD and should be screened for in assessing cardiac risk in asymptomatic individuals.
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PMID:Chronic renal dysfunction as an independent risk factor for the development of cardiovascular disease. 1570 61

The pathophysiology of the myelodysplastic syndromes (MDS) involves disturbed regulation of angiogenesis, apoptosis, proliferation and differentiation as well as immune surveillance. Increasing data suggest that sirolimus might affect these pathways positively, thus being of possible therapeutic benefit in patients with this disease. Nineteen patients (n = 19) with a median age of 72 years (range 54-80 years) diagnosed with MDS received sirolimus orally with a target blood concentration of 3-12 ng/ml. Sirolimus was administered for a median of 3.7 months (range 0.3-11 months). Three patients [1 x refractory anaemia with excess blasts (RAEB)-2, 1 x RAEB-1, 1 x refractory cytopenia with multilineage dysplasia] showed either a major (1 x platelet, 1 x neutrophil) or a minor (1 x erythroid, 2 x platelet) haematological response according to International Working Group criteria. Major side-effects were hyperlipidaemia (n = 4), stomatitis (n = 3), thrombocytopenia (n = 2) and urinary tract infection (n = 1). These data suggest that sirolimus has activity in a subset of patients with more advanced MDS.
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PMID:Activity of sirolimus in patients with myelodysplastic syndrome--results of a pilot study. 1572 83


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