High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients

Albitar, Sami; Genin, R; Fen-Chong, M; Serveaux, Marie-Odile; Bourgeon, B

doi:10.1093/ndt/13.5.1206

Cited by 116 publications

(89 citation statements)

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“…19 In our study, baseline Hgb in patients receiving ACE inhibitors was no different from that in patients not receiving them. Although the exact reason for this discrepancy with the literature is unclear, patients not receiving ACE inhibitors in Val-HeFT had more severe HF.…”

Section: Should Anemia In Hf Be Treated?contrasting

confidence: 46%

“…18 Use of ACE inhibitors may reduce Hgb by inhibiting erythropoietin synthesis. 19 Iron deficiency resulting from malabsorption, nutritional deficiencies, impaired metabolism, 20 and aspirin-induced gastrointestinal bleeding may contribute. Finally, hemodilution caused by an increase in plasma volume has been found to cause anemia in nearly half the patients with severe end-stage HF.…”

Section: Causes Of Anemia In Hfmentioning

confidence: 99%

See 1 more Smart Citation

Anemia and Change in Hemoglobin Over Time Related to Mortality and Morbidity in Patients With Chronic Heart Failure

Anand¹,

Kuskowski²,

Rector³

et al. 2005

Circulation

237

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for the Val-HeFT InvestigatorsBackground-Anemia is known to be a prognostic marker for patients with heart failure. However, little is known about the prognostic value of changes in hemoglobin (Hgb) over time or about the causes of anemia. Methods and Results-Retrospective analysis of Valsartan Heart Failure Trial data indicated that the quartile of patients with the biggest average decrease in Hgb over 12 months (from 14.2 to 12.6 g/dL) had significantly (PՅ0.01) increased risk of subsequent hospitalization (hazard ratio [HR], 1.47), morbid events (HR, 1.41), and death (HR, 1.6) compared with the quartile that exhibited little change in Hgb over 12 months (from 13.7 to 13.8 g/dL). Increasing Hgb was significantly associated with lower mortality in patients with (HR, 0.78) and without (HR, 0.79) anemia at baseline. Anemia at baseline and the changes in Hgb were independently associated with serum albumin, blood pressure, glomerular filtration rate, B-type natriuretic peptide, and C-reactive protein.Lack of anemia at baseline and increases in Hgb over 12 months were not associated with smaller left ventricular diameters or higher ejection fractions. Conclusions-Changes in Hgb over 12 months were inversely associated with subsequent risk of mortality and morbidity, independently of the effects of baseline anemia and other important predictors. Several factors were independently related to anemia at baseline and changes in Hgb, suggesting multiple causes of anemia in patients with heart failure. These findings raise important questions about the optimal level of Hgb in patients with moderate to severe heart failure and how to achieve them. Key Words: anemia Ⅲ angiotensin receptor blockers Ⅲ hemoglobin Ⅲ natriuretic peptides Ⅲ prognosis T here is increasing evidence that anemia is common in patients with heart failure (HF) 1,2 and is correlated with increases in mortality and morbidity. 2-4 However, it remains unclear whether changes in hemoglobin (Hgb) over time are also related to the risk of morbid events and mortality. Moreover, neither the factors that cause anemia in HF nor the mechanisms that worsen HF in anemic patients are well understood. Whereas chronic anemia can lead to high-output failure, 5,6 it is unclear whether anemia is a cause or a consequence of the low-output HF.A number of small clinical studies have shown that treatment of anemia with erythropoietin in patients with HF is clinically beneficial. 7,8 However, therapeutic measures to increase Hgb may worsen hemodynamics, 5,9 and raising hematocrit above 42% increased cardiovascular mortality in a large randomized trial. 10 More recently, at least 4 clinical trials in Europe were stopped prematurely because of excessive vascular events in the erythropoietin-treated group. 11,12 These data therefore raise concerns as to whether Hgb should be raised in patients with HF and questions about the ideal level to be achieved.The Valsartan Heart Failure Trial (Val-HeFT) 13 database was analyzed to address some of the unanswered questions about anemia and ...

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Section: Should Anemia In Hf Be Treated?contrasting

confidence: 46%

Section: Causes Of Anemia In Hfmentioning

confidence: 99%

Anemia and Change in Hemoglobin Over Time Related to Mortality and Morbidity in Patients With Chronic Heart Failure

Anand¹,

Kuskowski²,

Rector³

et al. 2005

Circulation

237

View full text Add to dashboard Cite

show abstract

“…In addition, ACE inhibitors may impair erythropoiesis via either suppression of angiotensin-mediated Epo production or bone marrow response to Epo [53]. The relationship between the use of ACEI and ERI is still controversial, some investigations showed no relationship [54][55][56] while others [57,58] confirmed this study's finding and showed reduction in response to ESA. This study showed a positive significant association between statins use and ERI.…”

Section: Individual Response Variations To Erythropoietin Stimulatingsupporting

confidence: 69%

Individual Response Variations to Erythropoietin Stimulating Agents in Patients on Maintenance Hemodialysis.

Ebid¹,

Elsawy²,

Taha³

2017

IOSRJPBS

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“…These studies have disagreed as to the role of ACE inhibitors on erythropoietin production and effectiveness (4). Some groups suggest that ACE inhibitors reduce erythropoietin levels or induce resistance to erythropoietin (6,22,23,26). Other studies find no causative link between erythropoietin and the anemia induced by ACE inhibitors or AT 1 receptor antagonists (3,24,27,28).…”

Section: Figurementioning

confidence: 99%

Lack of angiotensin II–facilitated erythropoiesis causes anemia in angiotensin-converting enzyme–deficient mice

et al. 2000

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IntroductionThe renin-angiotensin system plays a critical role in blood pressure regulation and fluid hemodynamics. Pharmacologic inhibitors of this system are routinely used to treat hypertension and congestive heart failure. One of the most controversial effects of the reninangiotensin system has been the interplay of this system with erythrocyte production. A variety of clinical reports have noted an association between activation of the renin-angiotensin system and increased erythropoiesis (1-3). These studies have come from analyses of patients with a variety of chronic diseases including chronic obstructive pulmonary disease, heart failure, and renal transplantation. Other investigators have suggested a link between angiotensin-converting enzyme (ACE) inhibitors and worsened anemia, particularly in patients with chronic renal failure (4-6). While research has focused on the interplay of the renin-angiotensin system and erythropoietin, no mechanistic explanation for these observations has been generally accepted.Central to the renin-angiotensin system is ACE, a peptidase that converts angiotensin I to angiotensin II (7). In mammals, most ACE is bound to tissues such as endothelium, but enzymatic cleavage results in a circulating form within plasma. In vitro, ACE is capable of cleaving many small peptides besides angiotensin I. However, in vivo, with the exception of bradykinin, the significance of nonangiotensin peptides as ACE substrates is not well understood. ACE is a protein with two independent catalytic domains. While both catalytic sites hydrolyze angiotensin I with roughly equal efficiency, the amino-and carboxy-terminal catalytic domains differ in their rate constants for other peptides.Using targeted homologous recombination in embryonic stem (ES) cells, our laboratory created two lines of mice with modifications of the ACE gene (8, 9). These animals are termed ACE.1 and ACE.2. Mice homozygous for the ACE.1 allele (ACE.1 knockout mice) are null for all ACE production. They have a marked reduction of blood pressure, and a renal lesion characterized by hypoplasia of the renal medulla and papilla. In contrast to this null phenotype, animals homozygous for the ACE.2 allele (ACE.2 knockout mice) have a partial restoration of ACE activity. These animals express a truncated ACE protein containing only the amino-terminal catalytic domain. Since this shortened ACE protein lacks the carboxy-terminal domain that normally anchors ACE to cell membranes, the ACE.2 protein is exported from cells into blood and other extracellular fluids. Thus, while the plasma of ACE.2 mice converts angiotensin I to angiotensin II with about 34% of the activity of wild-type mouse plasma, tissues such as the lung and kidney completely lack ACE protein or activity. The systolic blood pressure of ACE.2 knockout mice averaged 75 mmHg, as low as that of the ACE.1 knockout animals.Here, we investigate an unexpected finding concerning the phenotypes of both the ACE.1 and ACE.2 mice. These animals are anemic. ACE.2 knockout mice are a p...

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High dose enalapril impairs the response to erythropoietin treatment in haemodialysis patients

Abstract: High-dose enalapril increases rHuEpo requirement and should be reserved for dialysis patients with hypertension uncontrollable with other antihypertensive medications or dialysis patients with cardiac failure.

Cited by 116 publications

References 1 publication

Anemia and Change in Hemoglobin Over Time Related to Mortality and Morbidity in Patients With Chronic Heart Failure

Anemia and Change in Hemoglobin Over Time Related to Mortality and Morbidity in Patients With Chronic Heart Failure

Individual Response Variations to Erythropoietin Stimulating Agents in Patients on Maintenance Hemodialysis.

Lack of angiotensin II–facilitated erythropoiesis causes anemia in angiotensin-converting enzyme–deficient mice

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