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13 Erythropoietin intheTreatment ofAnaemia
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13.4 Erythropoietin Production inCKD
Insufciently low EPO levels are associated with severe anaemia in patients with
chronic kidney disease (CKD). CKD begins with an EPO deciency, but it seems to
get worse when the estimated glomerular ltration rate (eGFR) is reduced below
30mL per minute per 1.73m2 (Wenger and Hoogewijs 2010). A reduction in EPO
production or mistakes in EPO sensing may be the cause of an absolute EPO shortage. Reduced blood ow to the kidneys causes an imbalance in oxygen delivery,
which is linked to chronic kidney disease (CKD). Renal tissue adapts as a result,
consuming less oxygen and allowing the tissue oxygen gradient to remain normal.
PHD enzymes continue to function as a result, and neither the HIF heterodimer nor
the EPO gene is activated. Empirical evidence has shown the presence of cytokines
such as transforming growth factor-beta (TGF-β), interleukin-lβ (IL-lβ), IL-la, and
tumour necrosis factor (TNF)-α decrease the generation of EPO caused by hypoxia
(Fandrey and Jelmann 1991). The immunological activation molecule hypoxiainduced EPO is suppressed, and it is well known that CKD causes an increase in
inammation (Rao etal. 2007; Souma etal. 2016).
13.5 Role ofErythropoietin inCKD-Related Anaemia
EPO has the capacity to stimulate the differentiation and proliferation of bone marrow cells. It serves as a humoral factor that facilitates the generation of RBCs.
Furthermore, EPO has the ability to enhance the production of haemoglobin,
increase blood circulation in peripheral arteries, and encourage the process by
which stem cells may develop into RBCs. To facilitate the transformation of the red
line into fully developed RBCs, the hormone EPO activates EPO receptors, which
in turn promote the differentiation and proliferation of burst-forming unit-erythroid
(BFU-E) cells. This chapter basically highlights the role of erythropoietin agents in
the treatment of anaemia in CKD patients along with patients with diabetic anaemia, CHF anaemia, and inammatory bowel disease anaemia (Batchelor etal. 2020).
13.6 Types ofVarious Erythropoietin Stimulating Agent Use
inCKD Anaemia
The clinical management of CKD-induced anaemia has been signicantly
improved with the introduction of the rst human recombinant EPO, especially
for dialysis patients. ESA therapy accounted for 11% of all Medicare ESRD costs
in 2004 and was the greatest single Medicare drug expenditure in the USA, with
a total of US$1.8 billion. There are three generations of EPO agents: rst generation, second generation, and third generation. The rst-generation EPO agents
have a shorter half-life and require frequent dosing. Hence, second-generation
EPOs are modied with a higher short life to reduce the frequent dose timing.
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Table 13.1 Various erythropoietin agents' generation for clinical use in CKD anaemia
Manufacturing
company Agent name Generation Marketing agency
Ortho biotech Epoetin alfa (Procrit) First US
Amgen Epoetin alfa (Epogen) First US
Janssen-Ortho Epoetin alfa (Eprex) First Worldwide except US
Roche Epoetin beta (NeoRecormon) First Europe
Amgen Darbepoetin (Aranesp) Second North America, Europe,
Roche Erythropoietin receptor
activator
Third US
Canada
N. Ghosh et al.
Recently, third- generation EPO agents have been modied into ESA agents for a
better therapeutic effect, and it is also known as EPO receptor activators (Eschbach
etal. 1989; Macdougall 2008). There are several EPO agents that are available in
the market (Table13.1).
13.7 Role ofErythropoietin withCombination Drug
Therapy inCKD Anaemia
13.7.1 Iron Sucrose
Clinically, there are two main categories for administering iron supplements: oral
and intravenous. Oral delivery is often insufcient to fully full the iron needs in the
bone marrow of individuals with uraemia and diseases related to iron release and
absorption in the gastrointestinal tract. On the other hand, intravenous iron supplementation has a relatively high utilisation rate and few gastrointestinal side effects
(Van Wyck etal. 2005). This can boost iron reserves and enhance iron use, helping
to get beyond the reticuloendothelial system’s iron release barrier. In the reticuloendothelial system, active macrophages help release iron ions from intravenous iron
complexes. Iron utilisation in the body increases when a portion of the iron combines with apoferritin to produce serum ferritin reserves inside cells and when
another portion of the iron connects with transferrin-to-transferrin receptors located
on the surface of juvenile red blood cells. Clinical observation has demonstrated
that starting with EPO treatment and gradually increasing the iron sucrose treatment
can both signicantly improve clinical efcacy and improve symptomatic treatment
by mitigating the adverse reaction to low and mild levels of the sugar iron treatment
(Xue etal. 2015).
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13.7.2 L-Carnitine
L-carnitine is an amino acid that is widely distributed throughout the tissues of the
body. The compound has the potential to impact the acylation and phospholipid
processes as well as the deformability of the erythrocyte membrane. Additionally, it
can stabilise the membrane of RBCs and increase the number of red blood cells in
order to improve the body’s ability to withstand different types of pressures. A
shortage of L-carnitine at the cell level can have harmful effects, shorten life expectancy, raise normal red cell osmotic fragility, and perhaps lead to EPO resistance. In
patients who are in remission, L-carnitine has been shown to reduce microinammation, tumour necrosis factor (TNF), interleukin 1 (IL-1), and C-reactive
protein (CRP), effectively decreasing renal anaemia (Boran etal. 1996; Emami
Naini etal. 2012).
13.7.3 Iron Dextran
An intravenous iron preparation is known as iron dextran. Patients with anaemia
who get erythropoietin treatment have imbalanced iron storage and excessive iron
consumption. IV iron supplementation has good efcacy, yet there is a risk of both
acute adverse reactions and delayed reactions that resemble allergic reactions.
These reactions include hypotension, urticaria, chest discomfort, respiratory issues,
and vasogenic oedema. When iron dextran dispersion tablets are used in conjunction with erythropoietin and L-carnitine injection, the effectiveness of EPO is
greatly increased. As a consequence, there is a drop in EPO levels, a notable
enhancement in the condition of anaemia, a reduction in adverse effects, and a
decrease in dialysis syndrome (Larramendi etal. 2006).
13.7.4 Reduced Glutathione
Persons with chronic renal failure have decreased antioxidant activity, increased
oxidant activity, and a buildup of metabolic products, leading to reduced levels of
glutathione and increasing amounts of oxidised glutathione. Disulde linkages are
created by molecules in the membrane of red blood cells, resulting in the aggregation of macromolecules on the membrane and causing deformation of the RBCs.
The three-peptide complex glutathione is made up of glycine, cysteine, and glutamic acid. It serves as a signicant metabolic regulator inside the cell. It may
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provide cysteine and thiol while preserving the cell’s normal metabolic and physiological processes, hence preserving the integrity of the cell membrane (Zachara
etal. 2006). Furthermore, it may eliminate lipid peroxide by interacting with proelectron or reactive-oxygen species, protecting the cell. Exogenous reductive glutathione treatment for chronic renal failure has many potential benets, including
stabilising the membrane of red blood cells, increasing their longevity, decreasing
levels of oxidised glutathione, and improving red blood cell reduction. Supplemental
reductive glutathione, as opposed to EPO alone, has profound effects on anaemia,
according to studies (Ghorbani etal. 2016).
N. Ghosh et al.
13.7.5 Irbesartan andEnalapril
Patients with various forms of renal anaemia and hypertension suffer from
chronic renal insufciency. Angiotensin-converting enzyme can be inhibited
with enalapril, which hydrolyses into enalapril and lowers the amount of angiotensin II (AT-II), alleviating hypertension by relaxing blood arteries and decreasing blood pressure. Irbesartan, an AT- II receptor blocker, inhibits the vascular
angiotensin-converting enzyme (ACE) 1 receptor, thereby preventing the conversion of vascular angiotensin I to angiotensin II (Peters etal. 2015). It lowers
blood pressure by directly inhibiting the binding of ACE-1 receptors and angiotensin II, resulting in reduced constriction of blood vessels and decreased release
of aldosterone. Patients undergoing haemodialysis for chronic renal illness who
are treated with enalapril and irbesartan have higher haemoglobin and red blood
cell counts, although these increases were not as great as those shown in the
group that only used EPO once. To guarantee that enalapril is successful, hypertensive individuals with chronic renal function disorders need to be administered the proper dose of erythropoietin (Ordaz- Medina etal. 2010).
13.7.6 Vitamin C
Vitamin C (ascorbic acid) is uptaken by the body via the upper section of the
small intestine after dissolving in water. For reducing metabolic oxidative stress,
vitamin C is absolutely essential. Vitamin C has a crucial role in the production
of collagen, the prevention of scurvy, maintaining gum and dental health, preventing muscle wasting, inhibiting artery hardening, synthesising antioxidants,
and treating anaemia. Iron consumption in the liver is enhanced by vitamin C,
which also lowers ferric iron and increases intestinal iron absorption. Lack of
vitamin C lowers dialysis clearance in certain haemodialysis patients (Eiselt
etal. 2001).
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13.8 Route ofAdministration
When providing ESA to patients with CKD, the administration route should be
considered. Research indicates that the subcutaneous approach is generally more
economical than the intravenous approach, requires fewer injections overall, and
minimises the need for extra support after injections. Despite this, since ESA may
be comfortably given during dialysis, a lot of dialysis patients and possibly nephrology professionals choose the intravenous method. For example, most dialysis
patients in the USA take ESA therapy intravenously. However, the option is
restricted to subcutaneous administration in peritoneal dialysis patients and in the
non-dialysis CKD population since patients are frequently told to use the least intrusive, subcutaneous, mode of injection at home without supervision. If a patient still
fails to respond well to intravenous ESA administration after their dose is adjusted,
they may consider switching to the subcutaneous method. The subcutaneous dose
should be lowered by 30% when considering this move to prevent the chance of an
abrupt increase in haemoglobin levels above target (Tonelli etal. 2003).
13.9 Risk Ratio ofTreatment withESA
Agent-Related Hypertension
About 5% of individuals may experience an increase in hypertension after using an
ESA, necessitating a change in dosage or another ESA.Seldom does complete ESA
withdrawal become essential in the age of innovative and potent antihypertensive
therapy. It is believed that the mechanism of ESA-induced hypertension involves
ESA stimulating the vascular endothelium, which raises endothelin levels in the
blood. Furthermore, vasospasm may develop from an increase in blood viscosity
brought on by the haemoglobin increase linked to ESA medication. Thus, it is
essential that patients getting ESA medication have their blood pressure checked on
a regular basis (Public Health Advisory; Information for Healthcare Professionals)
(Krapf and Hulter 2009).
13.10 Role ofErythropoietin Agent inCHF Patient
withAnaemia
With almost half a million new cases each year, congestive heart failure (CHF) is a
fast-expanding public health issue that affects approximately ve million people in
the USA alone. Seniors have the highest prevalence of CHF; ten out of every 1000
people over 65 have the condition. One modiable concomitant condition of heart
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failure has been identied as anaemia. Based on the World Health Organization’s
(WHO) denition of anaemia, which is dened as haemoglobin <13g/dL in men
and<12g/dL in women, it has been estimated that up to 55% of CHF patients had
anaemia overall, and up to 79% of patients with advanced, New York Heart
Association (NYHA) class IV CHF (Silverberg et al. 2008). Anaemia has been
related to adverse outcomes such as left ventricular dilatation and hypertrophy, as
well as an increase in heart failure. Renal insufciency is a typical occurrence in
people with CHF; up to 50% of patients have renal impairment. As renal failure
progresses, circulating erythropoietin levels drop, which in turn lowers haemoglobin levels and bone marrow erythrocyte synthesis. The EPO gene has been assigned
a specic location on human chromosome 7, namely at position 7q21. The therapeutic use of recombinant EPO was rst introduced in 1987 for patients suffering
from anaemia caused by chronic renal insufciency (Anand 2008).
N. Ghosh et al.
13.11 Anaemia inPatients withCongestive Heart Failure
CHF-associated anaemia, despite being quite prevalent and having negative implications, may not receive sufcient recognition. About 22% of patients in the
extensive Studies of Left Ventricular Dysfunction (SOLVD) experiment were
diagnosed with anaemia. The severity of anaemia was directly linked to higher
mortality rates. Lower haemoglobin levels were associated with a higher risk of
mortality or hospitalisation for people with chronic heart failure, according to the
ndings of a different study named Outcome of Prospective Trial of Intravenous
Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF).
Specically, for every 1g/dL decrease in haemoglobin, there was a 12% increased
risk (Silverberg etal. 2006). There are numerous factors that can produce anaemia
linked with CHF.CHF is a persistent inammatory condition characterised by
signicant increases in cytokines, including interleukins and TNF-α. The presence of these inammatory cytokines hinders the generation and effectiveness of
EPO.Additionally, they have the potential to impede the release of iron from tissue reserves. In addition, the enlargement of the heart and the associated kidney
dysfunction might lead to a dilution of the blood. Anaemia in congestive heart
failure can potentially be caused by the pharmacological medications administered for the treatment of heart failure. Angiotensin receptor blockers (ARBs) and
angiotensin-converting enzyme (ACE) inhibitors are the backbone of contemporary treatment. These drugs can disrupt the production of red blood cells either by
directly suppressing bone marrow activity or by reducing the effectiveness of the
erythropoietin receptor. The administration of ACE inhibitors or ARBs in individuals with hypertension may lead to a reduction in haemoglobin levels of up to
0.3mg/dL. Additional possible factors that can contribute to the condition are
prolonged aspirin use leading to blood loss in the gastrointestinal system and
bowel oedema causing reduced absorption of iron and other nutrients (Groenveld
et al. 2008a). Furthermore, the reduced synthesis of EPO that occurs in
13 Erythropoietin intheTreatment ofAnaemia
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conjunction with chronic renal illness can potentially be a contributing factor to
the development of anaemia. On the other hand, having a high level of creatinine
in the blood is a signicant and separate factor that increases the risk of death in
individuals with heart failure. Uraemia is linked to a higher accumulation of atherosclerotic plaque and, as a result, a greater occurrence of coronary lesions and
events. The main cause of death for individuals with end-stage renal disease
(ESRD) is cardiovascular events. Anaemia is made worse by chronic kidney disease (CKD), which increases the chance of heart failure (Nemeth 2008).
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13.12 Growth Factor’s Role inTreating
CHF-Linked Anaemia
The implementation of EPO has had a substantial inuence on the treatment of
anaemia. Initially, EPO was employed for the treatment of anaemia in individuals
with ESRD.Afterwards, the focus has turned towards its utilisation in anaemia due
to congestive heart failure (National Kidney Foundation 2006). The implementation
of neuro-hormonal inhibition in current therapy for CHF has led to substantial
reductions in both morbidity and death. Nevertheless, addressing anaemia linked
with CHF may result in further advantages. Echocardiograms in anaemic patients
with chronic renal insufciency who received EPO treatment showed a reduction in
left ventricular (LV) mass and a decrease in LV dilatation. An experiment conducted
by Silverberg etal. (2002) examined anaemic patients with advanced CHF who
were treated with EPO and intravenous (IV) iron (Silverberg etal. 2002). The study
found that an increase in haemoglobin (Hb) levels was linked to improvements in
left ventricular ejection function (LVEF), a reduction in functional class, and a
decrease in the frequency of hospitalisations. In a separate trial conducted by
Mancini etal. (2003), anaemia was treated by administering EPO and oral ferrous
gluconate (Mancini et al. 2003). This treatment resulted in improved exercise
parameters, as seen by an elevation in peak oxygen consumption levels (VO2). In
addition to its ability to improve anaemia, EPO also provides other benets that are
not related to the production of red blood cells. It reduces the occurrence of programmed cell death in cardiac muscle cells. Recruiting endothelial progenitor cells
improves the formation of new blood vessels, known as angiogenesis, and consequently promotes neovascularisation (Groenveld etal. 2008b). Patients with CHF
may experience positive effects from the latter option due to the amelioration of
ischaemia associated with coronary and cerebrovascular atherosclerosis. Because it
may lower levels of cytokines and interleukins, EPO may have an anti-inammatory
effect. Hence, EPO may prevent myocardial infarction (MI) damage from progressing any further. The retina and other brain tissues have also shown evidence of EPO
receptors. Animal studies have shown that EPO may help prevent kidney and central
nervous system (CNS) damage caused by acute ischaemia. Comparable results have
been observed in patients treated with darbepoetin for both anaemia and CHF.The
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preliminary results of a randomised, double-blind experiment that was carried out
across several sites suggested that darbepoetin alfa raised haemoglobin levels,
which improved quality of life (Tanner etal. 2002).
13.13 Conclusions
ESA treatment is recommended for anaemia in individuals with CKD to enhance
the quality of life and reduce morbidity and death. Several concerns highlighted in
this article must be considered while administering ESA for the treatment of anaemia in CKD. Moreover, as growing data indicate ESA medication may not be
entirely harmless, it is crucial to strictly follow instructions and maintain haemoglobin levels within the suggested target ranges. Regularly monitoring the patient is
necessary to enhance overall outcomes. Despite the use of appropriate pharmaceutical management, CHF remains a signicant public health issue. Anaemia associated
with CHF is a signicant coexisting condition that, when addressed, might potentially reduce the chances of heart failure. The administration of growth factors has
been linked to increased levels of haemoglobin, which in turn has been related to
better outcomes in patients with advanced heart failure. Effective identication and
treatment of this disease may require the cooperation of primary care physicians,
nephrologists, and cardiologists. We need further research on the impact of growth
factors on mortality and morbidity, the cost-efciency of darbepoetin and EPO, and
other topics. This should be done through larger studies that are randomised, doubleblind, and placebo-controlled. Furthermore, the ideal goal levels for Hb have not
been determined.
References
Anand IS (2008) Anemia and chronic heart failure. J Am Coll Cardiol 52(7):501–511
Barany H-J (2007) Muller maintaining control over hemoglobin levels: optimizing the manage-
ment of anemia in chronic kidney disease. Nephrol Dial Transplant 22:iv10–iv18
Batchelor EK, Kapitsinou P, Pergola PE, Kovesdy CP, Jalal DI (2020) Iron deciency in chronic
kidney disease: updates on pathophysiology, diagnosis, and treatment. J Am Soc Nephrol
31:456–468. https://doi.org/10.1681/ASN.2019020213
Boran M, Dalva I, Gonenc F, Cetin S (1996) Response to recombinant human erythropoietin (r-Hu
EPO) and L-carnitine combination in patients with anemia of endstage renal disease. Nephron
73:314–315
Brugnara C (2003) Iron deciency and erythropoiesis: new diagnostic approaches. Clin Chem
49:1573–1578
Collins AJ, Ma JZ, Ebben J (2000) Impact of hematocrit on morbidity and mortality. Semin
Nephrol 20:345
Eiselt J, Racek J, Trel L, Opatrny K Jr (2001) Effects of a vitamin E-modied dialysis membrane
and vitamin C infusion on oxidative stress in hemodialysis patients. Artif Organs 25:430–436
13 Erythropoietin intheTreatment ofAnaemia
https://t.me/med1917
Emami Naini A, Moradi M, Mortazavi M, Amini Harandi A, Hadizadeh M, Shirani F, Basir
Ghafoori H, Emami NP (2012) Effects of oral L-carnitine supplementation on lipid prole,
anemia, and quality of life in chronic renal disease patients under hemodialysis: a randomized,
double-blinded, placebo-controlled trial. J Nutr Metab 2012:1
Eschbach JW, Kelly MR, Haley NR etal (1989) Treatment of the anemia of progressive renal
failure with recombinant human erythropoietin. N Engl J Med 20:158–163
Fandrey J, Jelmann WE (1991) Interleukin-1 and tumor necrosis factor-alpha inhibit erythro-
poietin production in vitro. Ann N Y Acad Sci 628:250–255. https://doi.org/10.1111/j.1749-
6632.1991.tb17252.x
Ghorbani M, Vatannejad A, Khodadadi I, Amiri I, Tavilani H (2016) Protective effects of glutathi-
one supplementation against oxidative stress during cryopreservation of human spermatozoa.
Cryo Letters 37:34–40
Groenveld HF, Januzzi JL, Damman K etal (2008a) Anemia and mortality in heart failure patients:
a systematic review and meta-analysis. J Am Coll Cardiol 52(10):818–827
Groenveld HF, Januzzi JL, Damman K etal (2008b) Anemia and mortality in patients with heart
failure a systematic review and meta-analysis. J Am Coll Radiol 52:818–827
KDIGO Anemia Working Group (2012) KDIGO clinical practice guideline for anemia in chronic
kidney disease. Kidney Int 2:279–335. https://doi.org/10.1038/kisup.2012.38
Krapf R, Hulter HN (2009) Arterial hypertension induced by erythropoietin and erythropoiesis-
stimulating agents (ESA). Clin J Am Soc Nephrol 4:470
Larramendi CH, Marco FM, Garcia-Abujeta JL, Mateo M, de la Vega A, Sempere JM (2006)
Acute allergic reaction to an iron compound in a milk-allergic patient. Pediatr Allergy Immunol
17:230–233
Macdougall IC (2008) Novel erythropoiesis-stimulating agents: a new era in anemia management.
Clin J Am Soc Nephrol 3:200–207
Mancini DM, Katz SD, Lang CC et al (2003) Effect of erythropoietin on exercise capacity in
patients with moderate to severe chronic heart failure. Circulation 107:294–299
National Kidney Foundation (2006) KDOQI Clinical practice guidelines and clinical practice rec-
ommendations for anemia in chronic kidney disease. Am J Kidney Dis 5:S1–S3
Nemeth E (2008) Iron regulation and erythropoiesis. Curr Opin Hematol 15(3):169–175
Ordaz-Medina SM, Gonzalez-Plascencia J, Martin del Campo F, Rojas-Campos E, Montanez-
Fernandez JL, Espinoza-Gomez F, Cueto-Manzano AM (2010) Is systemic inammation of
hemodialysis patients improved with the use of enalapril? Results of a randomized, double-
blinded, placebo-controlled clinical trial. ASAIO J 56:37–41
Pan X, Suzuki N, Hirano I, Yamazaki S, Minegishi N, Yamamoto M (2011) Isolation and char-
acterization of renal erythropoietin- producing cells from genetically produced anemia mice.
PLoS One 6:e0025839. https://doi.org/10.1371/journal.pone.0025839
Peters CD, Kjaergaard KD, Jensen JD, Christensen KL, Strandhave C, Tietze IN, Novosel MK,
Bibby BM, Jespersen B (2015) Short and long-term effects of the angiotensin II receptor
blocker Irbesartan on intradialytic central hemodynamics: a randomized double-blind placebo-
controlled one-year intervention trial (the SAFIR study). PLoS One 10:e0126882
Provenzano R, Besarab A, Sun CH, Diamond SA, Durham JH, Cangiano JL et al (2016) Oral
hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat (FG-4592) for the treatment
of anemia in patients with CKD.Clin J Am Soc Nephrol 11:982–991. https://doi.org/10.2215/
CJN.06890615
Rankin EB, Rha J, Selak MA, Unger TL, Keith B, Liu QHV (2009) Hypoxia-inducible factor
2 regulates hepatic lipid metabolism. Mol Cell Biol 29:4527–4538. https://doi.org/10.1128/
MCB.00200- 09
Rao M, Wong C, Kanetsky P, Girndt M, Stenvinkel P, Reilly M etal (2007) Cytokine gene poly-
morphism and progression of renal and cardiovascular diseases. Kidney Int 72:549–556.
https://doi.org/10.1038/sj.ki.5002391
Silverberg DS, Wexler D, Iaina A (2002) The importance of anemia and its correction in the man-
agement of severe congestive heart failure. Eur J Heart Fail 4:681–686
277
278
https://t.me/med1917
Silverberg DS, Wexler D, Iaina A, Schwartz D (2006) The interaction between heart failure and
other heart diseases, renal failure, and anemia. Semin Nephrol 26(4):296–306
Silverberg DS, Wexler D, Iaina A, Schwartz D (2008) The role of correction of anaemia in patients
with congestive heart failure: a short review. Eur J Heart Fail 10(9):819–823
Souma T, Nezu M, Nakano D, Yamazaki S, Hirano I (2016) Erythropoietin synthesis in renal
myo broblasts is restored by activation of hypoxia signaling. JASN 27:428–438. https://doi.
org/10.1681/ASN.2014121184
Tanner H, Moschovitis G, Kuster GM etal (2002) The prevalence of anemia in chronic heart fail-
ure. Int J Cardiol 86:115–121
Tonelli M, Winkelmayer WC, Jindal KK etal (2003) The cost-effectiveness of maintaining higher
hemoglobin targets with erythropoietin in hemodialysis patients. Kidney Int 64:295–304
Van Wyck DB, Roppolo M, Martinez CO, Mazey RM, McMurray S, United States Iron Sucrose
Clinical Trials G (2005) A randomized, controlled trial comparing IV iron sucrose to oral iron
in anemic patients with nondialysis-dependent CKD.Kidney Int 68:2846–2856
Wenger RH, Hoogewijs D (2010) Regulated oxygen sensing by protein hydroxylation in renal
erythropoietin-producing cells. Am J Physiol Ren Physiol 298:F1287–F1296. https://doi.
org/10.1152/ajprenal.00736.2009
Xue CE, Shen QH, Wang Y, Zhang JY, Lin FR (2015) Clinical signicance of the serum EPO level
in patients with iron deciency anemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 23:1410–1414
Zachara BA, Gromadzinska J, Wasowicz W, Zbrog Z (2006) Red blood cell and plasma glutathi-
one peroxidase activities and selenium concentration in patients with chronic kidney disease: a
review. Acta Biochim Pol 53:663–677
N. Ghosh et al.
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