Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin-converting enzyme (ACE) inhibitor therapy has recently been shown to be effective in the treatment of post-renal transplant erythrocytosis (PTE). In an attempt to assess the effect of drug treatment on serum erythropoietin level, glomerular filtration rate, and urinary protein excretion, we prospectively evaluated 8 consecutive cadaveric renal transplant recipients with PTE treated with ACE inhibitor therapy for 3 months. In response to ACE inhibition, the mean hematocrit (HCT) value decreased from 53.7 +/- 0.6% before treatment to 42.7 +/- 2.2% at the conclusion of the study (p = 0.03). However, 1 patient failed to respond to ACE inhibition (HCT > 50%), and 2 patients with PTE developed anemia (HCT < 35%) while maintained on drug treatment. Although the mean serum erythropoietin level decreased during ACE inhibition (from 22.8 +/- 8.4 to 9.4 +/- 5.3 mU/ml; p = 0.06), a consistent change in individual erythropoietin levels was not identified. At the conclusion of the study, the serum erythropoietin levels were undetectable in 4 patients, decreased in 1, unchanged in 2, and increased in the only patient with PTE who failed to respond to drug treatment. All patients tolerated the ACE inhibitor therapy without developing cough or hyperkalemia. In addition, serum creatinine levels, 125I-iothalamate clearances, and mean arterial blood pressures were unchanged throughout the study. Microalbuminuria (spot urinary albumin/creatinine ratio between 30 and 200 mg/g) developed in 5 patients with PTE and coincided with the onset of erythrocytosis (25.2 +/- 7 mg/g before PTE and 76.3 +/- 36.7 mg/g at the time of PTE detection).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of post-renal transplant erythrocytosis and microalbuminuria: response to angiotensin-converting enzyme inhibition. 757 90

Exacerbation of anemia associated with angiotensin-converting enzyme (ACE) inhibitor therapy has been noted to occur in patients with chronic renal failure, end-stage renal disease, and renal transplantation. Angiotensin-converting enzyme inhibitors appear to cause anemia through induction of decreased red blood cell production. There are data suggesting that ACE inhibitors may impair erythropoiesis via either suppression of angiotensin-mediated erythropoietin (EPO) production or bone marrow response to EPO. Patients on chronic hemodialysis receive recombinant human EPO (rHuEPO) for therapy of anemia and may also receive an ACE inhibitor for hypertension or congestive heart failure. We undertook a retrospective study to evaluate whether patients treated with ACE inhibitors developed a more severe anemia or required a higher dose of rHuEPO to maintain a similar hematocrit. Ninety-five of 108 chronic hemodialysis patients met study criteria (hemodialysis for 4 months and no treatment with an ACE inhibitor for at least 4 months = group 1; therapy with an ACE inhibitor for at least 4 months = group 2). Forty-eight patients (group 1, n = 24; group 2, n = 24) were available for analysis after exclusion for a variety of factors. There was no difference between the two groups in terms of baseline characteristics, number of blood transfusions or hospital days, or other laboratory parameters. There was no statistically significant difference in average hematocrit between group 1 (33.5% +/- 3.9%) and group 2 (32.6% +/- 1.6%). Similarly, no significant difference was observed for the average rHuEPO dose/treatment between group 1 (3,272 +/- 1,532 IU/treatment; 50.69 +/- 26.94 IU/kg/treatment) and group 2 (3,401 +/- 1,009 IU/treatment; 52.87 +/- 19.38 IU/kg/treatment). These results suggest that ACE inhibitors do not significantly induce more severe anemia or alter rHuEPO response in chronic hemodialysis patients.
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PMID:Angiotensin-converting enzyme inhibitor therapy in chronic hemodialysis patients: any evidence of erythropoietin resistance? 884 Sep 43

Fifty-two patients with postrenal transplant erythrocytosis were treated with an angiotensin-converting enzyme inhibitor (lisinopril or enalapril) for a median of 13 months (range 0-44). A significant fall in haemoglobin of 1.8 +/- 1.6 g dl-1 (range - 0.8 to 6.6) occurred over the first 3 months (p < 0.0001). The haemoglobin then remained stable for as long as 3 years. Both enalapril and lisinopril were equally effective. Therapy was withdrawn in 16 patients (31%) because of decline in renal function (6), anaemia (5), hypotension (3), hyperkalaemia (1) or erectile impotence (1) - complications which were all reversible. Angiotensin-converting enzyme inhibitors in low dose are a safe and effective long-term therapy for postrenal transplant erythrocytosis.
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PMID:Treatment of postrenal transplant erythrocytosis. Long-term efficacy and safety of angiotensin-converting enzyme inhibitors. 893 74

Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.
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PMID:Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects. 937 Jan 81

Angiotensin-converting enzyme (ACE) inhibitors may exacerbate anemia in patients with chronic renal failure, as well as in dialysis patients. To better answer this question, a prospective, crossover study was conducted to evaluate the effect of ACE inhibitors on recombinant human erythropoietin (rHuEPO) requirements in hemodialysis patients. Patients administered an ACE inhibitor when entering the study remained on this drug for the initial 4 months and were then switched to another antihypertensive agent for 4 more months. Patients not initially administered an ACE inhibitor were switched to lisinopril at 4 months. rHuEPO doses were adjusted using a sliding scale based on weekly laboratory hematocrit values. The inclusion criteria were met by 51 patients undergoing dialysis. Demographics were as follows: 61% were women, 64% were black, 46% had diabetes, average age was 53.2 +/- 13.3 years, and time on hemodialysis was 38.0 +/- 44.5 months. Thirty-three patients completed the study. Hematocrit averaged 32.7% +/- 1.9% while on ACE inhibitor therapy and 33.1% +/- 2.1% off ACE inhibitor therapy (P = 0.217). There was no difference in rHuEPO dose per treatment during each period (3,500 +/- 1,549 U on ACE inhibitor therapy versus 3,312 +/- 1,492 U off ACE inhibitor therapy; P = 0.300). No significant differences were found in degree of blood pressure control or various clinical and laboratory parameters that might be associated with rHuEPO resistance between the two periods. Similarly, no differences were found in hospitalization days, duration of infections, or transfusion requirements. These findings suggest that ACE inhibitors do not contribute to rHuEPO resistance in hemodialysis patients.
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PMID:ACE inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients. 1100 96

Angiotensin-converting enzyme (ACE) produces the vasoconstrictor angiotensin II. The ACE protein is composed of two homologous domains, each binding zinc and each independently catalytic. To assess the physiologic significance of the two ACE catalytic domains, we used gene targeting in mice to introduce two point mutations (H395K and H399K) that selectively inactivated the ACE N-terminal catalytic site. This modification does not affect C-terminal enzymatic activity or ACE protein expression. In addition, the testis ACE isozyme is not affected by the mutations. Analysis of homozygous mutant mice (termed ACE 7/7) showed normal plasma levels of angiotensin II but an elevation of plasma and urine N-acetyl-Ser-Asp-Lys-Pro, a peptide suggested to inhibit bone marrow maturation. Despite this, ACE 7/7 mice had blood pressure, renal function, and hematocrit that were indistinguishable from wild-type mice. We also studied compound heterozygous mice in which one ACE allele was null (no ACE expression) and the second allele encoded the mutations selectively inactivating the N-terminal catalytic domain. These mice produced approximately half the normal levels of ACE, with the ACE protein lacking N-terminal catalytic activity. Despite this, the mice have a phenotype indistinguishable from wild-type animals. This study shows that, in vivo, the presence of the C-terminal ACE catalytic domain is sufficient to maintain a functional renin-angiotensin system. It also strongly suggests that the anemia present in ACE null mice is not due to the accumulation of the peptide N-acetyl-Ser-Asp-Lys-Pro.
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PMID:Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice. 1475 57

The majority of end-stage renal disease (ESRD) patients are hypertensive. Drug therapy for hypertension in hemodialysis (HD) patients includes all classes of antihypertensive drugs, with the sole exception of diuretics. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers may decrease morbidity and mortality by reducing the mean arterial pressure (MAP), aortic pulse wave velocity, and aortic systolic pressure augmentation, as well as left ventricular hypertrophy (LVH) and probably reduction of C-reactive protein (CRP) and oxidant stress. Potential risk factors include hyperkalemia, anaphylactoid reaction with AN69 membranes (particularly ACE inhibitors), and aggravation of renal anemia. beta-blockers decrease not only mortality, blood pressure (BP), and ventricular arrhythmias, but also improve left ventricular function in ESRD patients. Nonselective beta-blockers can cause an increase in serum potassium (particularly during fasting or exercise). Lisinopril and atenolol have a predominant renal excretion and therefore a prolonged half life in ESRD patients. Thus thrice-weekly supervised administration of these drugs after HD can enhance BP control. The use of calcium channel blockers is also associated with lower total and cardiovascular-specific mortality in HD patients. Minoxidil is a very potent vasodilator that is generally reserved for dialysis patients with severe hypertension. Hypertensive dialysis patients who are noncompliant with their medications may benefit from transdermal clonidine therapy once a week. The majority of dialysis patients need a combination of several antihypertensive drugs for adequate BP control.
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PMID:Drug therapy for hypertension in hemodialysis patients. 1525 Sep 20

Inactivation of the gene encoding mouse angiotensin I-converting enzyme (ACE), which converts angiotensin I into angiotensin II, results in anemia in adult animals. This anemia is corrected by angiotensin II, demonstrating the involvement of angiotensin II in adult (definitive) erythropoiesis. We investigated the possible role of the renin-angiotensin system (RAS) in primitive erythropoiesis in the yolk sac of the chicken embryo. Enzymatically active ACE was detected in the yolk sac endoderm, concomitantly with the differentiation of blood islands in the adjacent yolk sac mesoderm. The simultaneous presence of all the other components of the RAS (renin, angiotensinogen, angiotensin II receptor) in the vicinity of the blood islands suggests that this system is involved in erythropoiesis. This role was confirmed by in vivo blockade of the RAS with fosinoprilate, a specific inhibitor of chicken ACE, which decreased hematocrit by 15%. A similar decrease in hematocrit was observed following treatment with the angiotensin II receptor antagonist Sar1-Ile8-Angiotensin II, suggesting that this effect was mediated by angiotensin II. Both treatments affected hematocrit by decreasing erythroblast proliferation. Thus, the RAS, and its effector peptide angiotensin II in particular, modulates primitive erythropoiesis.
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PMID:Role of the renin-angiotensin system in primitive erythropoiesis in the chick embryo. 1536 38

Chronic kidney disease is a progressive condition that results in significant morbidity and mortality. Because of the important role the kidneys play in maintaining homeostasis, chronic kidney disease can affect almost every body system. Early recognition and intervention are essential to slowing disease progression, maintaining quality of life, and improving outcomes. Family physicians have the opportunity to screen at-risk patients, identify affected patients, and ameliorate the impact of chronic kidney disease by initiating early therapy and monitoring disease progression. Aggressive blood pressure control, with a goal of 130/80 mm Hg or less, is recommended in patients with chronic kidney disease. Angiotensin-converting enzyme inhibitors and angiotensin-II receptor antagonists are most effective because of their unique ability to decrease proteinuria. Hyperglycemia should be treated; the goal is an AIC concentration below 7 percent. In patients with dyslipidemia, statin therapy is appropriate to reduce the risk of cardiovascular disease. Anemia should be treated, with a target hemoglobin concentration of 11 to 12 g per dL (110 to 120 g per L). Hyperparathyroid disease requires dietary phosphate restrictions, antacid use, and vitamin D supplementation; if medical therapy fails, referral for surgery is necessary. Counseling on adequate nutrition should be provided, and smoking cessation must be encouraged at each office visit.
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PMID:Chronic kidney disease: prevention and treatment of common complications. 1557 Oct 58

Heart failure affects 5 million persons in the United States, with 400,000 new cases occurring every year. Paradoxically, although advances in coronary angioplasty and effective drugs have increased survival post infarction, the myocardial damage and subsequent neurohormonal activation-induced remodeling causes significant morbidity years later in the form of heart failure. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) together with beta blockers modify the neurohormonal activation associated with heart failure and are key treatments for improving cardiac function and survival. Anemia is a significant risk factor predicting morbidity and mortality in heart failure. This article describes the various etiologies of anemia in heart failure. Of particular importance is the fact that recent stem cell studies have shown that the drugs acting on the renin-angiotensin system inhibit erythropoiesis in vivo and may cause anemia in patients with both normal renal function and end-stage renal disease (ESRD). The role of angiotensin-II as an erythropoietic growth factor and ACE in facilitating erythropoiesis is described in this article. Anemia has been shown to be a modifiable risk factor and its treatment correlates with improvement in clinical outcomes. Thus, anemia, its etiology (especially the contribution of ACEIs and ARBs), physiologic and prognostic impact, and treatment in the setting of heart failure are critical areas for investigation.
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PMID:Anemia in heart failure--a concise review. 1627 92


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