Effect of Angiotensin-Converting Enzyme Inhibitors on Response to Erythropoietin Therapy in Chronic Dialysis Patients

Charytan, Chaim; Goldfarb–Rumyantzev, Alexander S.; Wang, Y.F.; Schwenk, Michael H.; Spinowitz, Bruce

doi:10.1159/000013394

Cited by 27 publications

(23 citation statements)

References 21 publications

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“…Angiotensin II modulation of erythropoietin production is hypothesized to occur via activation of AT1 receptors and/or altered renal hemodynamics (Gossmann et al, 2001;Benohr et al, 2004). However, other studies found no causative link between erythropoietin and anemia induced with ACE inhibitors or AT1 receptor antagonists (Perazella et al, 1995;Charytan et al, 1998;Chew et al, 1999). Second, angiotensin II is a mitogen for erythroid progenitors.…”

Section: G Erythropoiesismentioning

confidence: 99%

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

et al. 2012

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Section: G Erythropoiesismentioning

confidence: 99%

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

et al. 2012

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“…In our study there was no significant difference between pre and post hospitalization intact parathyroid hormone levels. Angiotensin converting enzyme (ACE) has been linked to the Epo resistance in the previous studies [28] but in more recent studies there was no difference in Epo requirements in hemodialysis patients administered ACE inhibitors versus those administered other antihypertensive medications [29,30]. We did not look at the impact of various antihypertensive agents on the Epo requirements.…”

Section: Discussionmentioning

confidence: 98%

Erythropoietin Requirements Increase following Hospitalization in End-Stage Renal Disease Patients

Yaqub

Leiser

Molitoris³

2001

Am J Nephrol

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The effect of hospitalization on an ESRD patient’s hemoglobin (Hgb) level and erythropoietin (Epo) requirement has not been investigated. We postulated patients with end stage renal disease required an increased Epo dose to maintain stable Hgb during hospitalization and for a period following discharge. To evaluate this hypothesis, we conducted a retrospective chart review on 65 hemodialysis patients. All hemodialysis patients admitted for more than 2 days who did not have more than the index hospitalizations for 2 months prior to and following discharge were included. Multiple parameters including Hgb, Epo dose, intravenous iron dose, serum iron, TIBC, and ferritin during the 2 months before and the two months after hospitalization, Hgb at admission and discharge, Hgb trough, surgery, blood transfusions and co-morbid factors were evaluated. Statistical significance was evaluated using ANOVA or rank-sum testing, as appropriate. In 65 hemodialysis patients (24 M/41 F, age 58 ± 2.2 years, mean ± SEM), Hgb levels following discharge and for 2 subsequent months were significantly lower than 2 months prior to admission (11.4 ± 0.25 vs. 10.7 ± 0.22 g/dl, p < 0.01). This occurred in spite of an increase in Epo dose (128 ± 14 vs. 185 ± 21 U/kg/week, p < 0.0001) over this 2-month period. There was no difference in the iron saturation before and after hospitalization (22 vs. 23%,p > 0.05). There were also no apparent effects of comorbid factors, including surgery, or discharge diagnosis on the changes in Hgb or Epo requirements. However, patients who required a blood transfusion during the hospitalization had lower Hgb levels and higher Epo doses both prior to and after hospitalization, as well as lower Hgb trough levels. In addition, females had lower Hgb levels than males both prior to and after hospitalization, and were receiving a higher Epo dose 191 ± 18 vs. 129 ± 20 U/kg/week at 1 month and 215 ± 18 U/kg/week vs. 134 ± 22, p < 0.005 at 2 months after hospitalization. Conclusion: This study points out that hemodialysis patients experience a significant and prolonged decrease in Hgb levels after hospitalization, even despite a moderate increase in Epo dosing.

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“…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). ACE.2 knockout mice are an excellent model system for studying the role of the renin-angiotensin system in erythropoiesis (9).…”

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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Effect of Angiotensin-Converting Enzyme Inhibitors on Response to Erythropoietin Therapy in Chronic Dialysis Patients

Cited by 27 publications

References 21 publications

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

Erythropoietin Requirements Increase following Hospitalization in End-Stage Renal Disease Patients

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

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