Treatment of the Anemia of Progressive Renal Failure with Recombinant Human Erythropoietin

Eschbach, Joseph W.; Kelly, McKayla; Haley, Nancy; Abels, Robert I.; Adamson, John W.

doi:10.1056/nejm198907203210305

Cited by 461 publications

(172 citation statements)

References 20 publications

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“…137 Hypertension is common with erythropoietin therapy, with approximately 30% of patients either developing hypertension or requiring an adjustment in antihypertensive medications. 138,139 The etiology of hypertension with erythropoietin therapy is not clear. The incidence of erythropoietin-induced hypertension correlates with the erythropoietin dose but appears to be independent of its effect on red blood cell mass and viscosity.…”

Section: Nonvolume-dependent Causes Of Hypertension In Dialysis Patientsmentioning

confidence: 99%

Assessment and Management of Hypertension in Patients on Dialysis

Agarwal

Flynn

Pogue

et al. 2014

Journal of the American Society of Nephrology

161

156

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Hypertension is common, difficult to diagnose, and poorly controlled among patients with ESRD. However, controversy surrounds the diagnosis and treatment of hypertension. Here, we describe the diagnosis, epidemiology, and management of hypertension in dialysis patients, and examine the data sparking debate over appropriate methods for diagnosing and treating hypertension. Furthermore, we consider the issues uniquely related to hypertension in pediatric dialysis patients. Future clinical trials designed to clarify the controversial results discussed here should lead to the implementation of diagnostic and therapeutic techniques that improve long-term cardiovascular outcomes in patients with ESRD. Hypertension is common among patients with ESRD. In this review, we discuss the diagnosis, epidemiology, and management of hypertension among dialysis patients. We also review areas of existing controversies and briefly discuss the issue of hypertension in pediatric dialysis patients. EPIDEMIOLOGYThe prevalence, treatment, and control of hypertension among people on hemodialysis (HD) have used varying definitions to diagnose hypertension. The epidemiology differs based on how BP is measured: either before and after dialysis or using ambulatory BP recordings. Epidemiology with Routine BP MeasurementsThe prevalence of hypertension (defined as 1-week average predialysis systolic BP [SBP] measurements .150 mmHg or diastolic BP [DBP].85 mmHg or the use of antihypertensive medications) was 86% among 2535 clinically stable adult HD patients participating in a multicenter trial. 1 Among hypertensive patients, 12% did not receive antihypertensive drugs, 58% were treated but not controlled, and only 30% were controlled. The use of antihypertensive drugs has been reported to vary from 59% to 83%. [2][3][4][5] Furthermore, even among children on long-term HD, similar findings have been reported. 6 Several studies have confirmed greater antihypertensive drug use to be associated with poorer control. 7,8 It should be noted that antihypertensive drug use per se do not lead to worse BP control; in the absence of adequate volume control, increasing antihypertensive drug use may simply reflect difficult-to-control BP. Epidemiology Using Ambulatory BP MeasurementsThe prevalence of hypertension (defined by either a 44-hour interdialytic ambulatory BP of $135/85 mmHg or the prescription of any antihypertensive agent) was 86% among 369 chronic HD patients. 8 Although hypertension was being treated with antihypertensive drugs in 89% of patients, it was adequately controlled only in 38%. The independent determinants of poor control were the use of antihypertensive drugs and an expanded extracellular volume state. If patients were volume overloaded, nearly 80% became hypertensive when medications were Published online ahead of print. Publication date available at www.jasn.org.

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Section: Nonvolume-dependent Causes Of Hypertension In Dialysis Patientsmentioning

confidence: 99%

Assessment and Management of Hypertension in Patients on Dialysis

Agarwal

Flynn

Pogue

et al. 2014

Journal of the American Society of Nephrology

161

156

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“…Most patients who undergo hemodialysis (HD) therefore are treated with recombinant human erythropoietin (r-HuEPO) (1,2). The most important confounding factor limiting the effectiveness of rHuEPO is absolute or functional iron deficiency.…”

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confidence: 99%

Non–Transferrin-Bound Iron in the Serum of Hemodialysis Patients Who Receive Ferric Saccharate

Scheiber-Mojdehkar

Lutzky²,

Schaufler³

et al. 2004

Journal of the American Society of Nephrology

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Abstract. Intravenous iron (iv.Fe) is used to optimize response to recombinant human erythropoietin (r-HuEPO) in ESRD, but no consensus exists with respect to the best regimen to avoid transferrin "oversaturation," oxidative stress, and the occurrence of non-transferrin-bound iron (NTBI). Iv.Fe was stopped for 1 wk in 35 hemodialysis (HD) patients who were routinely receiving iv.Fe and r-HuEPO. The iv.Fe group received 100 mg of ferric saccharate (Venofer) at the end of the first HD session, whereas the time-control group was treated under the same conditions but received no iv.Fe. Serum samples were taken before the first HD session, immediately and 60 min after iv.Fe administration, and before the next HD session. Sera were analyzed for NTBI and peroxides; transferrin saturation was analyzed by urea-PAGE and Western blot. In an in vitro model system with HepG2 cells, the effects of ESRD serum on the labile iron pool (LIP) were assayed using the fluorescence calcein assay. NTBI significantly increased after iv.Fe-administration and returned to baseline values before the next HDsession. There was a shift from apo-to monoferric transferrin, but no "oversaturation" of transferrin after iv.Fe-treatment. Peroxides increased in both groups after HD. Hemodialysis decreased bioavailable iron for the LIP in HepG2-cells, whereas serum of iv.Fe-treated HD patients highly increased the LIP in these cells. A total of 100 mg of iv.Fe led to NTBI generation but not to an oversaturation of transferrin. Peroxide concentrations significantly increased during HD but were not correlated to iv.Fe administration and seemed to result from other sources of oxidative stress related to HD. NTBI can enter liver cells and increase the potentially harmful LIP.

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“…Recombinant human erythropoietin (epoetin-a) treatment increases blood hemoglobin levels in almost all patients with anemia of ESRD and has been a mainstay of managing these patients for decades (1)(2)(3)(4)(5)(6). Both intravenous (iv) and subcutaneous (sc) epoetin effectively ameliorate anemia of kidney failure.…”

Section: Introductionmentioning

confidence: 99%

Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States

Wright¹,

Wright

Narva

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Recombinant human erythropoietin (epoetin) is used routinely to increase blood hemoglobin levels in patients with ESRD and anemia. Although lower doses of epoetin are required to achieve equivalent hemoglobin responses when administered subcutaneously rather than intravenously, standard practice has been to administer epoetin to patients on hemodialysis intravenously. Randomized trials of alternative epoetin treatment regimens in patients with kidney failure have shown that risks of cardiovascular complications and death are related to the dose levels of epoetin used. Therefore, given the dose-sparing advantages of subcutaneous epoetin administration, the possibility that treatment of patients on hemodialysis with subcutaneous epoetin might be associated with more favorable outcomes compared with intravenous treatment was investigated.Design, setting, participants, & measurements A retrospective cohort study of 62,710 adult patients on hemodialysis treated with either intravenous or subcutaneous epoetin-a and enrolled in the Centers for Medicare and Medicaid Services ESRD Clinical Performance Measures Project from 1997 to 2005 was carried out. Risks of death and/or hospitalization for cardiovascular complications (adverse composite event outcomes) during 2 years of follow-up were determined in relationship to epoetin dose and route of administration (intravenous versus subcutaneous) by multivariate Cox proportional hazard modeling adjusted for demographics and clinical parameters.Results Epoetin doses used to achieve equivalent hemoglobin responses in study patients were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously (as expected). Moreover, adverse composite event outcomes were found to be significantly more likely to occur during follow-up for patients on hemodialysis managed with intravenous rather than subcutaneous epoetin (adjusted hazard ratio for adverse events within 1 year [intravenous versus subcutaneous] was 1.11 [95% confidence interval, 1.04 to 1.18]).Conclusions This study finds that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment.

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Treatment of the Anemia of Progressive Renal Failure with Recombinant Human Erythropoietin

Cited by 461 publications

References 20 publications

Assessment and Management of Hypertension in Patients on Dialysis

Assessment and Management of Hypertension in Patients on Dialysis

Non–Transferrin-Bound Iron in the Serum of Hemodialysis Patients Who Receive Ferric Saccharate

Association of Erythropoietin Dose and Route of Administration with Clinical Outcomes for Patients on Hemodialysis in the United States

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