Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anemia in children after renal transplantation is more common than previously appreciated. Multiple factors appear to play roles in the development of post-transplant anemia, the most common of which is absolute and/or functional iron deficiency anemia. Most experts recommend that iron limited anemias in transplant patients should be diagnosed using the same criteria as for chronic renal failure patients. Serum erythropoietin (EPO) levels are expected to normalize after a successful renal transplantation with a normal kidney function, yet both EPO deficiency and resistance have been reported. While no large controlled trials comparing the effect of different immunosuppressive agents on erythropoiesis after transplantation have been performed, generalized bone marrow suppression attributable to azathioprine (AZA), mycophenolate mofetil (MMF), tacrolimus, antithymocyte preparations has been reported. Pure red cell aplasia (PRCA) occurs rarely after transplantation and is characterized by the selective suppression of erythroid cells in the bone marrow. PRCA has been reported with the use of AZA, MMF, tacrolimus, angiotensin converting enzyme inhibitors (ACEI), but not with cyclosporine (CSA) use. Post-transplant hemolytic uremic syndrome has been reported with orthoclone anti T-cell antibody (OKT3), CSA and tacrolimus therapy. Viral infections including cytomegalovirus, Epstein-Barr virus and human parvovirus B19 have been reported to cause generalized marrow suppression. Management of severe anemia associated with immunosuppressive drugs generally requires lowering the dose, drug substitution or, when possible, discontinuation of the drug. Because this topic has been incompletely studied, our recommendation as to the best immunosuppressive protocol after renal transplantation remains largely dependent on the clinical response of the individual patient.
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PMID:Anemia in children after transplantation: etiology and the effect of immunosuppressive therapy on erythropoiesis. 1289 2

Anemia (Hemoglobin of < 12 to 13 g/dl) is frequently encountered in patients with congestive heart failure (CHF). This anemia may be partly due to hemodilution, partly to the associated reduction in renal function, and partly to the use of ACE inhibitors and aspirin. However, there is evidence that CHF alone--through excessive cytokine production may also reduce the bone marrow and cause anemia. In several recent studies anemia has been found to be associated with a more severe degree of CHF, a higher rate of death, renal failure, hospitalization and evidence of malnutrition. In both uncontrolled and controlled studies correction of anemia with erythropoietin with or without the addition of i.v. iron has been attempted. The correction of anemia has been associated with a marked improvement in New York Heart Association (NYHA) functional cardiac class and Left Ventricular Ejection Fraction, a marked reduction in the need for hospitalization and high dose oral and i.v. diuretics, and an improvement in exercise capacity, peak exercise oxygen utilization and quality of life. The serum creatinine, which had been increasing steadily before treatment, stabilized with the correction of anemia. All this suggests that control of anemia in CHF could become a valuable addition to the therapeutic armamentarium of CHF and might also play a major role in the prevention of progressive renal failure.
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PMID:The cardio renal anemia syndrome: correcting anemia in patients with resistant congestive heart failure can improve both cardiac and renal function and reduce hospitalizations. 1294 May 39

The aim of this study was to establish the prevalence of anemia in stable pediatric renal transplant recipients and to examine the association of anemia with renal function, immunosuppressants, angiotensin converting enzyme inhibitors, and growth, as well as iron, vitamin B(12), and folate stores. This is a cross-sectional study of the 50 renal transplant recipients currently followed at our center. Patient data were collected regarding hematological parameters, growth, medications, renal function, underlying renal disease, delayed graft function, episodes of rejection, and iron or erythropoietin therapy post transplantation. The mean hemoglobin level (Hb) was 110 g/l and the overall prevalence of anemia was 60%, including 30% who were severely anemic (Hb<100 g/l). There was a high rate of iron deficiency (34%) and serum iron was the parameter of iron metabolism most closely associated with anemia. Hb in patients with low serum iron was 90.7 g/l versus 114.4 g/l in those with normal serum iron ( P<0.01). Both univariate and multiple linear regression determined tacrolimus dose and creatinine clearance to be significant factors associated with anemia. Tacrolimus dose correlated with a 10 g/l reduction in Hb for every increase of tacrolimus dose of 0.054 mg/kg per day ( P=0.001). The dose of mycophenolate was positively correlated with Hb, but this was likely to be confounded by our practice of dose reduction in the setting of anemia. Angiotensin converting enzyme inhibitor use was not associated with anemia. Severely anemic patients tended to be shorter, with a mean Z-score for height of -1.8 compared with -0.9 for those with normal Hb ( P=0.02). Anemia is a significant and common problem in pediatric renal transplant patients. Deteriorating renal function is an important cause, but other factors like iron deficiency and immunosuppression are involved. Definition of iron deficiency is difficult and serum iron may be a valuable indicator. Medication doses, nutritional status, need for erythropoietin and iron, as well as poor graft function and growth require systematic scrutiny in the care of the anemic renal transplant recipient.
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PMID:Anemia in pediatric renal transplant recipients. 1500 19

Hypertension and anemia may be causes of left ventricular hypertrophy (LVH) in uremia but the molecular mechanism is not known. Uremia was induced in male Spraugue Dawley rats by 5/6 nephrectomy. The following groups of rats were studied for 6 weeks; uremic rats (U) fed ad. lib., control rats (C) pair-fed with U, U rats given hydralazine (100 mg/kg/day) (UH), U rats given erythropoietin (48 U/kg/week, i.p.) (UE). Both diastolic and mean arterial pressures are higher (P < 0.01) in U and UE compared with C whereas both pressures in UH were normalized. Hemoglobin in U was lower than in C, and was normalized in UE. U, UH and UE had higher heart weight/body weight ratios (HW/BW) as well as left ventricular weight/body weight ratios (LV/BW) compared with C (P < 0.01). Compared with U, UH has lower HW/BW and LV/BW (P < 0.05) and UE has normal HW/BW but lower LV/BW than U (P < 0.05). To see if the gene expression in uremic LVH is similar to that described in pressure overload LVH in which mRNA levels of angiotensin converting enzyme (ACE), transforming growth factor-beta1 (TGF-beta1), atrial natriuretic factors (ANF) and skeletal a- actin were increased, we measured these mRNA levels by Northern analysis. TGF-beta1, ACE and alpha-actin mRNA levels were not changed in all 4 groups. ANF mRNA in U and UE was increased 3 fold over C, and normalized in UH. Treatment of anemia with erythropoietin improved uremic LVH but did not change ANF mRNA; whereas treatment of hypertension with hydralazine normalized ANF mRNA but did not completely correct uremic LVH. Thus, gene expression in uremic LVH is distinct from that in pressure-overload LVH, suggesting that other unidentified factor(s) might be involved in uremic LVH.
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PMID:Gene expression in uremic left ventricular hypertrophy: effects of hypertension and anemia. 1527 37

Anemia is one of the most serious complications in patients on dialysis. Erythropoietin improves the anemia. However, erythropoietin resistance is sometimes encountered from causes such as functional iron deficiency, secondary hyperparathyroidism, blood loss, or interaction with other drugs. To clarify the interaction between erythropoietin and the renin-angiotensin system, we studied the maintenance dose of recombinant human erythropoietin (rHuEPO) in patients on continuous ambulatory peritoneal dialysis (CAPD) with and without angiotensin converting enzyme inhibitor (ACEIs), angiotensin II type I receptor blockers (ARBs), and calcium channel blockers. We divided 36 hypertensive patients on CAPD into three groups--an ACEI group (n = 12), an ARB group (n = 12), and a Ca channel blocker group (n = 12)--and then we compared the doses of rHuEPO required to maintain the patients' hematocrit (Hct) above 30%. In the Ca channel blocker group, the weekly dose of erythropoietin had not changed significantly at the end of the study (74 +/- 7 U/kg at the end vs. 76 +/- 8 U/kg at the start). The (oral) ACEI group needed a significantly higher weekly dose of erythropoietin at the end of the study (89 -/+ 9 U/kg at the end vs. 74 -/+ 8 U/kg at the start, p < 0.01). The (oral) ARB group also needed a significantly higher weekly dose of erythropoietin at the end of the study (82 -/+ 10 U/kg at the end vs. 76 +/- 8 U/kg at the start, p < 0.05). Furthermore, the weekly dose of erythropoietin required in the ACEI group was significantly larger than that required in the ARB group. We conclude that treatment with ACEIs and ARBs induces erythropoietin resistance in patients on CAPD. The inhibitory effect of ARBs on erythropoiesis is less than that of ACEIs.
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PMID:Erythropoietin resistance in patients on continuous ambulatory peritoneal dialysis. 1538 8

Diuretics, ACE inhibitors and betablockers form the cornerstone of pharmacological treatment of chronic heart failure (CHF), while angiotensin receptor blockers are gaining ground. However, despite optimal treatment CHF remains a syndrome with poor prognosis. For this reason, a large number of new agents have been developed as add-on treatment over the last few years. Vasopeptidase inhibitors, moxonidine, endothelin antagonists, vasopressin antagonists, and selective aldosterone antagonists, are some of the new agents that were designed to interfere with different neurohormonal pathways. Immunomodulating agents, growth hormone, caspase inhibitors, adrenomedullin, and erythropoietin have different modes of action, which in general are less understood. Although most of the agents exhibited efficacy in preclinical trials, the clinical results have not always been similarly positive. The results of trials involving vasopeptidase inhibitors, endothelin antagonists, immunomodulating agents, and growth hormone have been disappointing. Other compounds like caspase inhibitors, adrenomedullin, and vasopressin antagonists are still at the early stages of development. Currently, the two most promising agents seem to be erythropoietin and the selective aldosterone receptor blocker eplerenone. In the present article an overview of new pharmacological developments for CHF is given, and the clinical value of these developments is discussed.
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PMID:New pharmacological strategies in chronic heart failure. 1577 Apr 37

This retrospective review assesses the efficacy of darbepoetin alfa for treating anemia after renal transplantation. Patients were evaluated over a 12-week period, and efficacy was based on achieving hemoglobin >12 g/dL. Thirty-six patients were analyzed (53% male, 53% cadaveric allografts, median age 42.5 years). Baseline creatinine clearance ranged from approximately 15 to >100 mL/min. Most patients initiated darbepoetin alfa <3 months (50%) or >12 months (44%) after transplantation, 19% were previously receiving recombinant human erythropoietin (rHuEPO), and 47% were on concomitant ACE inhibitors. The majority of patients received either tacrolimus- (53%) or cyclosporine- (44%) based immunosuppression. Overall, 29 (81%) patients achieved the hemoglobin target with a mean time to response of 4.4 weeks. Neither the time to anemia onset, previous rHuEPO therapy, concomitant ACE inhibitor, allograft source, immunosuppressive regimen, nor degree of renal function affected the proportion of patients achieving the hemoglobin target, time to response or darbepoetin alfa dose requirement. Patients with anemia >12 months post-transplantation or on concomitant ACE inhibitors required a significantly longer duration of therapy. No adverse events associated with darbepoetin alfa therapy were detected. These results demonstrate that darbepoetin alfa is a safe and effective treatment for anemia in renal transplant recipients.
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PMID:A retrospective assessment of pre-treatment variables on the response to darbepoetin alfa after renal transplantation. 1599 44

Anaemia is a frequent complication of diabetic nephropathy. It has only recently been recognised that in diabetic patients anaemia is seen not only in preterminal renal failure, but also frequently in patients with only minor derangement of renal function. At any level of glomerular filtration rate (GFR) anaemia is more frequent and severe in diabetic compared to nondiabetic patients. A major cause of anaemia is an inappropriate response of erythropoietin to anaemia. Additional factors are iron deficiency and iatrogenic factors, e.g. ACE inhibitor treatment. When serum creatinine is still normal, the erythropoietin concentration is predictive of more rapid loss of glomerular function. When serum creatinine is elevated, the haemoglobin values are predictive of the rate of progression. It is currently under investigation whether reversal of anaemia attenuates the rate of progression. Because most of the late complications of diabetes (retinopathy, neuropathy, heart disease, peripheral arterial disease) involve ischaemic tissue damage, it would be intuitively plausible that treatment with human recombinant erythropoietin should be beneficial, but definite evidence for this hypothesis is currently not available.
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PMID:Diabetic nephropathy and anaemia. 1628 61

The need for erythropoietin (rhuEPO) or darbepoetin-alpha and iron is lower in patients undergoing peritoneal dialysis (PD) than in patients treated with hemodialysis (HD) because blood losses are reduced, residual renal function and elimination of inhibitors of erythropoiesis are improved and inflammation is less than in HD treatment. In addition, comorbidities of PD patients are probably lower than those of HD patients, and this factor may also contribute to anemia being less in PD patients than in those on HD. Furthermore, the frequency of blood transfusions is lower in PD patients, with or without rhuEPO treatment. However, in PD patients also, anemia is associated with hospitalization rate and mortality. Anemia can be corrected by subcutaneous injections of rhuEPO-beta (1-3 times per week) or darbepoetin-alpha (once a week or twice a month). Adjuvant treatment of anemia includes correction of iron deficiency by oral or intravenous iron, androgen substitution in elderly male PD patients and adequate calcitriol supplementation. Factors that may negatively influence anemia in PD patients are inflammation, infection, antihypertensive therapy with ACE inhibitors or angiotensin II blockers and neutralizing antibodies against rhuEPO or darbepoetin-alpha.
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PMID:[Anemia and its treatment in peritoneal dialysis patients]. 1643 36

Congestive heart failure (CHF) is a common clinical problem, especially affecting the elderly. Current strategies of neurohormonal blockade with medications like angiotensin converting enzyme inhibitors have improved morbidity and mortality, but further improvement in outcomes requires new strategies. Both anemia and chronic renal disease commonly accompany congestive heart failure; their close relationship, in which one disease exacerbates the other, has been termed the cardio-renal-anemia syndrome. Correction of anemia in CHF patients using recombinant erythropoietin is feasible; small studies suggest that anemic congestive heart failure patients may have improved morbidity with this therapy. Recent animal and human studies of erythropoietin have shown that its benefit may be derived from both hematological and newly discovered non-hematological properties. Anemia might soon be considered a modifiable risk factor for optimal CHF management.
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PMID:Congestive heart failure-related anemia and a role for erythropoietin. 1690 59


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