Review

Iron-Deficiency Anemia in CKD: A Narrative Review for

the Kidney Care Team
Debra Hain, Donna Bednarski, Molly Cahill, Amy Dix, Bryce Foote, Mary S. Haras, Rory Pace, and
Orlando M. Guti
errez

Anemia is a common complication of chronic kidney disease (CKD) and is associated with increased Complete author and article
mortality and reduced health-related quality of life. Anemia is characterized by a decrease in hemoglobin, the information provided before
references.
iron-rich protein that the body uses for oxygen transport. Iron is required to produce hemoglobin, and dis-
ruptions in the iron homeostasis can lead to iron-deficiency anemia. Management of anemia in individuals Correspondence to D. Hain
with CKD is typically performed by a team of physicians, nurse practitioners, physician assistants, or (dhain@health.fau.edu)
registered nurses. Throughout the care continuum, the management can be enhanced by multidisciplinary Kidney Med. 5(8):100677.
care, and individuals with CKD can benefit from the involvement of other specialties, with dietitians/nutri- Published online May 25,
tionists playing an important role. However, a key area of unmet clinical need is how to assess and address 2023.
iron-deficiency anemia. This review aims to provide an overview of iron-deficiency anemia in CKD and how doi: 10.1016/
this may be diagnosed and managed by the entire kidney care team, such as describing the mechanisms j.xkme.2023.100677
underlying iron homeostasis, the complications of iron-deficiency anemia, and the current challenges
associated with its diagnosis and treatment in CKD. Opportunities for each multidisciplinary team member
to add value to the care of individuals with CKD and iron-deficiency anemia are also described.

© 2023 The Authors. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article
under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

INTRODUCTION
Anemia is a common complication of chronic kidney
disease (CKD), which is associated with a significantly
heightened risk of cardiovascular morbidity and higher
mortality rates.1 Direct health care costs are higher in in-
dividuals with CKD and anemia than for those without
anemia. Many individuals experience poor health-related
quality of life (QoL: eg, fatigue and reduced productiv-
ity) and debilitating symptoms, such as cognitive impair-
ment, shortness of breath, dizziness, headaches, loss of
appetite, and depression.2-5 The overall prevalence of
anemia in CKD was estimated to be 15.4%, with the
prevalence of anemia increasing as the disease advances.1
Anemia is clinically defined as having low levels of
hemoglobin, the iron-rich protein in red blood cells
(RBCs) responsible for the transport of oxygen.6-8 In
particular, the Kidney Disease: Improving Global Out-
comes (KDIGO) anemia work group guidelines define
anemia in CKD as a hemoglobin concentration
of <13.0 g/dL in men and <12.0 g/dL in women9 (he-
moglobin concentrations are >13.5-17.5 g/dL in healthy
men and >12.0-15.5 g/dL in healthy women).10
The causes of anemia in CKD are multifaceted, but
anemia primarily results from erythropoietin deficiency or
iron deficiency. Although an in-depth discussion of the
multifactorial pathogenesis of anemia in CKD is outside the
scope of this review, we refer readers to the studies by
Batchelor et al,11 Ganz and Nemeth,12 and Coffey and
Ganz13 for more detailed reviews on the topic.
Anemia in individuals with CKD is considerably
undertreated, particularly in those with non–dialysis-
dependent (NDD) CKD.3,14 In a survey of 410 individuals
with NDD-CKD anemia in the United States, only 22.8%
reported being treated for anemia, with the most being
treated for anemia in later stages of CKD (stage 1, 12.1%;
stage 2, 16.2%; stage 3, 26.5%; stage 4, 20.7%; and stage
5, 43.0%).1 The undertreatment of anemia in individuals
with NDD-CKD also increases the need for blood trans-
fusions.15,16 Among kidney transplant candidates, trans-
fusions increase the possibility of allosensitization (ie, the
development of antibodies), which may preclude candi-
dates from being able to receive the transplant or may
cause transplant rejection altogether.9 These examples
highlight the importance of promptly diagnosing and
managing anemia in this population. Because of the
complexity of anemia in individuals with CKD, successful
treatment requires a multidisciplinary care team. These
specialists include physicians, nurse practitioners, physi-
cian assistants, registered nurses, dietitians, and pharma-
cists. Social workers and case managers or care
coordinators may also be involved, depending on indi-
vidual needs. Equipped with the right knowledge and plan
of action, a multidisciplinary team can play a vital role in
improving health outcomes in this population.
Molecular Mechanisms of Iron Homeostasis
Overview of normal iron homeostasis
Before addressing the importance of multidisciplinary
management of iron-deficiency anemia in CKD, it is
important to briefly revisit the molecular mechanisms of
normal iron homeostasis. Iron is a crucial physiological
element with a unique ability to both receive and transfer
electrons, thereby participating in several critical physio-
logical processes, such as cellular respiration, oxygen
transport, and storage. Because of the potential for excess
iron to cause severe oxidative stress and tissue damage,6,13

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 Hain et al

Figure 1. Overview of normal iron homeostasis. Iron is a key component of hemoglobin, which is used by RBCs to transport oxygen.
Approximately 24 mg of iron per day is necessary for RBC production. Dietary iron is absorbed by the enterocyte; w1 to 2 mg must
be replaced through gastrointestinal absorption per day. Iron binds to transferrin (an iron transport protein) in the blood. Transferrin
delivers iron to the bone marrow (site of hemoglobin formation and RBC production). Iron not found in the circulation is largely stored
in the liver and spleen bound to ferritin (an iron-storage protein). Iron is largely recycled from aged RBCs (w120 days old), which are
degraded by macrophages. Transferrin also binds to and transports the iron released from macrophages. EPO, erythropoietin; GI,
gastrointestinal; RBC, red blood cells.

iron is bound to iron transport proteins through tightly
regulated iron metabolism. Iron is an essential constituent
of hemoglobin molecules, which have a protein compo-
nent and an oxygen-binding heme-iron complex within
their α and β chains. Several hundred million hemoglobin
molecules, which transport oxygen throughout the body,
are contained in a single RBC.17
Dietary iron, in the form of either heme (ie, found only
in meat, poultry, seafood, and fish) or nonheme iron (ie,
found in plant-based foods such as grains, beans, vegeta-
bles, fruits, nuts, and seeds), is absorbed by the duodenal
enterocytes (comprising the first part of the small intes-
tine) and exported into the circulation, where it is bound
to transferrin (an iron transport protein). Iron is then
transported to the liver and spleen, where it is bound to
ferritin (an iron-storage protein found in macrophages) or
to the bone marrow, where it is used for erythropoiesis
(RBC production) (Fig 1).11,14,18 Under normal condi-
tions, the bone marrow generates w200 billion new RBCs
per day to match the number of old (senescent) RBCs
removed from the circulation.19,20 Erythropoiesis is
regulated by erythropoietin (a hormone that stimulates
RBC production), which is mainly produced by the kid-
neys and by the liver to a lesser extent.21,22 Iron stores are
replenished when macrophages in the spleen and liver
engulf and consume old RBCs, a process known as
phagocytosis, ultimately recycling their iron content,
which is used either for the production of new RBCs or
stored for future use.6,20,23 The recycling of RBCs in the
spleen and liver provides most of the body’s iron (20-
25 mg/d),whereas dietary absorption provides only 1-
2 mg/d of iron.20,22 Most of the body’s iron is stored in
ferritin, and w3 mg of iron can be found circulating
bound to transferrin, which must be turned over every few
hours to meet the daily requirements.21,23
Hepcidin as a key regulator of iron homeostasis
Hepcidin is the key hormonal regulator of iron homeo-
stasis through its effects on ferroportin,14 a protein that
exports iron from the inside of the cell to the outside of the
cell. Hepcidin controls the uptake of iron from the gut and
its release from the iron stores11,13,24 (Fig 2). Hepcidin
production is stimulated by increased iron uptake,
inflammation, and infection and is inhibited by iron

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Hain et al

Figure 2. Hepcidin regulates iron absorption and iron availability. Hepcidin production is stimulated in the liver in response to
increased iron uptake, inflammation, and infection (step 1); high levels of hepcidin result in limited iron availability because iron is
sequestered by the intestine and macrophages (step 2) ferroportin serves as an exporter of iron into circulation. Because of high levels
of hepcidin, ferroportin interacts with hepcidin, which results in endocytosis and degradation. The degradation of ferroportin leads to
impaired iron absorption and release from the iron-storage sites, which results in decreased red blood cell production (step 3).

deficiency and hypoxia (inadequate oxygen supply to
cells).11,24,25 Hepcidin is released from the liver cells into
the circulation and binds to the iron exporter ferroportin
that is located on the membranes of the small intestine,
macrophages, and liver cells. This binding ultimately
causes the degradation of ferroportin, preventing iron
export into the plasma21,26 and, in turn, sequestering iron
in iron-storage sites (liver cells and macrophages).
Causes of Iron Deficiency in CKD
Iron-deficiency anemia in individuals with CKD may result
from functional iron deficiency, absolute iron deficiency,
or both. The factors contributing to functional iron defi-
ciency are chronic inflammation and poor hepcidin clear-
ance seen in CKD, whereas absolute iron deficiency
includes poor gastrointestinal (GI) dietary iron absorption
and blood loss.27 Understanding the cause of iron defi-
ciency in individuals with CKD is crucial, and this knowl-
edge guides the most appropriate and effective plan of care.
Functional iron deficiency—CKD exacerbates iron
deficiency
Impaired kidney function resulting from CKD can lead to
reduced erythropoietin production and reduced RBC pro-
duction. Erythropoiesis-stimulating agents (ESAs), such as
epoetin alfa and darbepoetin alfa, which have been staple
treatments for anemia in CKD, commonly cause functional
iron deficiency because after each dose they transiently
increase erythropoiesis to a higher rate than would occur
naturally.27 Therefore, iron release into the circulation
from iron stores is not rapid enough to provide sufficient
iron to support the increased rate of erythropoiesis,
causing a relative deficiency of circulating iron.6,27 When
this occurs, it is known as functional iron deficiency.11 The
prevalence of functional iron-deficiency anemia in in-
dividuals with CKD is high, and this can be a difficult
clinical condition to manage. One way to mitigate this is
through iron supplementation, which is recommended for
individuals with CKD who are receiving ESAs to prevent
the development of iron deficiency.9 In addition, CKD
leads to a highly inflammatory state that can chronically
elevate hepcidin levels and result in dysregulation of iron
homeostasis. Hepcidin is a relatively small hormone pep-
tide that is degraded by the kidney and excreted in the
urine.25 Thus, increased hepcidin in CKD can result from
impaired kidney clearance, which correlates with poor
kidney function. Inflammatory cytokines, such as inter-
leukin (IL)-6, also directly induce hepcidin transcription.
Elevated hepcidin prevents the release of stored iron from
absorptive duodenal epithelial cells, macrophages, and
hepatocytes, reducing the availability of iron for erythro-
poiesis.28,29 This can cause high serum ferritin concen-
trations and low transferrin saturation (TSAT; defined as
plasma iron divided by the total iron-binding capacity ×
100), which can be characteristic of functional iron-
deficiency anemia (Fig 3).14,27

Kidney Med Vol 5 | Iss 8 | August 2023 | 100677 3


Figure 3. Functional versus absolute iron deficiency.6,11,14 Depending on its cause, iron deficiency can be categorized as absolute or
functional. Both forms of iron deficiency are common in CKD. CKD, chronic kidney disease; ESA, erythropoietin-stimulating agent;
GI, gastrointestinal; TSAT, transferrin saturation.
The hepcidin-induced blockade of iron further
limits responsiveness to erythropoietin because the dif-
ferentiation of erythroblasts (immature RBCs) to re-
ticulocytes (nearly mature RBCs) is an iron-dependent
process.11 Anemia of chronic inflammation is a common
cause of functional iron deficiency and can occur in in-
flammatory diseases other than CKD (in the absence of
therapy with ESAs).11 Anemia from chronic inflammation
may also be triggered by active infection, autoimmune
diseases, cancer, hypoxia, or genetic deficiencies.8,11,20 In
individuals with CKD and functional iron deficiency,
TSAT, which reflects circulating iron, may be ≤20.0%
because the bone marrow strips iron off the circulating
transferrin faster than it can be replenished from the iron
stores. Ferritin, which reflects stored iron, may be low or
elevated (Fig 3).9
Absolute iron deficiency
The functional iron deficiency observed in CKD contrasts
with absolute iron deficiency, which occurs when the total
body iron stores in the bone marrow, liver, and spleen are
depleted. Absolute iron deficiency in individuals with CKD
is defined by low circulating and stored iron, particularly
TSAT of ≤20.0% and ferritin of ≤100 ng/mL.6,27 Absolute
iron deficiency may be a result of poor dietary iron ab-
sorption in the GI tract, malnutrition, blood loss due to GI
bleeding, or frequent blood tests or hemodialysis (in
kidney failure) (Fig 3).11,27,30,31 Individuals with dialysis-
dependent CKD, particularly those treated with
4 Kidney Med Vol 5 | Iss 8 | August 2023 | 100677
Hain et al
hemodialysis, are particularly vulnerable to iron-deficiency
anemia owing to blood retained in the hemodialysis ma-
chine and tubing (as high as 2 g of iron per year).6,32
Medications used to treat individuals with CKD, for
example, renin–angiotensin-converting enzyme inhibitors,
may also disrupt erythropoiesis and inhibit dietary iron
uptake, causing iron-deficiency anemia.3
Iron-Deficiency Anemia and Morbidity and Mortality
Several large studies have reported that anemia in CKD is
associated with a higher risk of morbidity and mortality,
such as a higher prevalence or risk of cardiovascular disease,
congestive heart failure, kidney failure, hospitalizations,
and death.4,6,21,33-35 A longitudinal study of a large popu-
lation (w28,000) with CKD found that over a 5-year
period, congestive heart failure, coronary artery disease,
and diabetes were more prevalent in those who died and
that these individuals also showed a high baseline preva-
lence of anemia.33 A separate study in men with moderate
and severe CKD who were not yet treated with dialysis
(N=853) found that a lower hemoglobin level was signif-
icantly associated with higher non–dialysis-dependent
mortality and higher risk of kidney failure.34 Rates of
mortality, cardiovascular complications, and kidney failure
were highest in men with the most severe anemia (hemo-
globin concentration of <10.5 g/dL).34 The same findings
were reported by a separate research group that analyzed the
outcomes of 5885 individuals with CKD.4 Cognitive
impairment has also been associated with CKD, which may
Hain et al
Figure 4. Prescriptions for anemia management in US individuals with NDD-CKD with hemoglobin concentration of <11.0 g/dL.3
CKD, chronic kidney disease; ESA, erythropoietin-stimulating agent; IV, intravenous; NDD, non–dialysis-dependent.
be due to comorbid cerebrovascular disease, which
commonly occurs, and has also been linked to anemia.36
Anemia in CKD may also contribute to reduced QoL.37
In an example from a study in the United States and
Canada, higher hemoglobin levels were associated with
improved QoL domains of the Kidney Disease Quality of
Life questionnaire in 1186 individuals with NDD-CKD
stages 3-5. Because hemoglobin concentration increased
from <11 to 13 g/dL, significant improvements in varied
QoL domains were observed, suggesting a relationship
between hemoglobin level and QoL. However, the most
dramatic improvements in QoL domains occurred when
hemoglobin levels increased in the groups with a baseline
hemoglobin concentration of <11 g/dL and hemoglobin
concentration of 11-12 g/dL. In a separate real-world,
international study of 2121 individuals with NDD-CKD,
hemoglobin concentration of >12 g/dL were associated
with better health-related quality of life, higher odds of
being physically active, reduced odds of progression of
CKD, and greater survival.38 In addition, this study
demonstrated that even moderate anemia was associated
with poorer health-related quality of life, CKD progres-
sion, and mortality.38 Malnutrition is also a common
complication of CKD that has been associated with
impaired QoL and well-being39 in addition to its effect on
iron deficiency and anemia.
The effect of anemia in CKD on the clinical end points
discussed earlier highlights the importance of optimal
anemia management and the nuances that might exist in
this landscape. In this context, recent data suggest that
anemia in individuals with CKD may be undertreated and
that there are regional differences in anemia management.
For example, an international, prospective cohort study
conducted by the Chronic Kidney Disease Outcomes and
Practice Patterns Study (CKDopps) that was designed to
describe and evaluate variation in nephrologist-led CKD
practices reported that 68.0% of individuals with CKD in
the United States with a hemoglobin concentration
of <11.0 g/dL were not treated with iron or ESAs (Fig 4).
Kidney Med Vol 5 | Iss 8 | August 2023 | 100677
Furthermore, the CKDopps study also found considerable
differences between countries (Brazil, France, Germany,
and the United States) in the management of individuals
with NDD-CKD; for individuals with a hemoglobin con-
centration of <11.0 g/dL, <50.0% were prescribed either
iron or an ESA in France and the United States.3 The rea-
sons for undertreatment of iron-deficiency anemia in CKD
may be due to regional, practice, and clinician variability
in the monitoring of hemoglobin level and iron in those
with CKD. Early findings from the CKDopps study found
that a high percentage of individuals did not have their
iron indices measured.3 A more recent analysis from the
CKDopps study reported that the hemoglobin levels and
iron stores are measured less frequently than the guideline
recommendations across France, the United Kingdom,
Brazil, and the United States, with measurement occurring
more frequently in those with more advanced stages of CKD
and lower hemoglobin levels.3 The authors of the CKDopps
study noted that earlier treatment of iron-deficiency anemia
in CKD would potentially prevent the rapid worsening of
anemia observed in the period prelude to dialysis and may
be part of a broader strategy to reduce the high mortality
rates that characterize the early dialysis period.3
In individuals with CKD who are eligible for kidney
transplant, it is vital that they are prevented from receiving
transfusions or becoming transfusion-dependent because
of severely low hemoglobin levels. Transfusions for the
treatment of anemia in CKD can increase the risk of allo-
sensitization. Undertreatment of iron-deficiency anemia in
CKD may also result from challenges associated with the
reliable measurement of iron, poor absorption of iron
across the GI tract, tolerability issues related to iron sup-
plementation, and accurate measurement of response to
iron supplementation, resulting in persistent challenges in
the overall management of these individuals.
Assessment of anemia and iron status
The diagnosis of iron-deficiency anemia is essential to
ensure prompt treatment to correct the deficiency and
5
 Hain et al

Figure 5. A flow chart for the assessment, diagnosis, and management of iron-deficiency anemia in patients with CKD8,9,40 *For in-
dividuals with NDD-CKD who have hemoglobin concentrations of <10.0 g/dL, KDIGO recommends that the decision to initiate ESA
therapy be individualized based on the rate of decrease of the hemoglobin concentration, previous response to iron therapy, the risk
of needing a transfusion, the risks related to ESA therapy, and the presence of symptoms attributable to anemia. For individuals with
CKD, KDIGO suggests using ESA therapy to avoid hemoglobin concentration decreasing to <9.0 g/dL by initiating ESA therapy
when hemoglobin concentration is 9.0-10.0 g/dL. yOn the basis of individual symptoms and overall clinical goals such as avoidance
of transfusion and improvement in anemia-related symptoms and after exclusion of active infection and other causes of ESA hypo-
responsiveness. zBenefits of iron therapy should be balanced with risks of harm in individuals (eg, anaphylactoid/other acute reac-
tions and unknown long-term risks). **Disease settings of celiac disease, anemia of chronic disease, and autoimmune gastritis. CKD,
chronic kidney disease; ESA, erythropoiesis-stimulating agent; IV, intravenous; KDIGO, Kidney Disease Improving Global Outcomes;
NDD, non–dialysis-dependent; TSAT, transferrin saturation.

improve the accompanying anemia. All individuals with
CKD, particularly those with an estimated glomerular
filtration rate (eGFR) of <60 mL/min/1.73 m2 (stage ≥3
CKD), should be screened for anemia as part of their initial
evaluation after CKD diagnosis. The screening includes
measurements of proteins involved in iron metabolism,
with serum ferritin, hemoglobin level, and TSAT being
the main tests used.6,9 Tests commonly used for the
evaluation of anemia and their purposes are summarized
in Fig 5.40
The members of the patient care team can help identify
the various factors that may contribute to anemia in CKD
by using a person-centered approach.41 Although the he-
matologic and iron status should be evaluated, the
screening should also encompass baseline assessments such
as current medications (including all supplements), blood
pressure, pulse, and common symptoms of anemia (eg,
fatigue, dizziness, headaches, shortness of breath, and
chest pain).41 Dietitians can assess nutritional status, such
as appetite, GI symptoms, weight change, and 24-hour
dietary recall. If there is no dietitian on staff at the clin-
ical practice, referral of individuals with CKD to a dietitian
should be considered an important part of care.42
TSAT, serum ferritin, and hemoglobin levels are most
commonly used to evaluate iron-deficiency anemia in
clinical practice. The laboratory parameters defining iron-
deficiency anemia differ between individuals with CKD
with absolute or functional iron-deficiency anemia and
those with normal kidney function (Fig 5). CKD man-
agement guidelines recommend that the timing and fre-
quency of iron deficiency assessment should be guided by
symptoms, baseline hemoglobin level, rates of hemoglo-
bin decline, target hemoglobin level, and CKD stage.9
These recommendations are summarized in Fig 5.
An individual with CKD presenting with the clinical
signs and symptoms of iron-deficiency anemia should
undergo testing for iron deficiency. Therefore, all mem-
bers of the multidisciplinary care team must be able to
recognize these changes throughout the care continuum so
that treatment can be pursued.31 However, the nonspecific
nature of symptoms of anemia, such as fatigue and
headache, means that members of the care team must be
attuned to any changes in clinical indicators over the
course of an individual’s care, and communication
regarding findings between team members is key. Di-
etitians have very specialized knowledge and can assess for

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Hain et al
changes in symptoms, diet or appetite, energy levels, use
of supplements, and nutritional and functional status; any
findings may prompt an assessment of iron deficiency.43
Assessment may be performed by using validated,
evidence-based tools, and dietitians should reassess nutri-
tional status after the initial consultation as part of an
ongoing, dynamic aspect of care. Social workers may take
note of changes in appetite or food access that can affect
nutrition and potentially trigger or worsen iron deficiency.
Social workers can also leverage their training and tools
to assess for depression, which may be associated with
anemia. Pharmacists may pay particular attention to any
changes in prescribed medications. For anyone involved in
the care of individuals with CKD, a physical examination of
the individual, such as looking for specific changes in nails,
hair, conjunctiva, and oral mucosa, may aid in the diag-
nosis of deficiency of iron, folate, or vitamin B12. Pica
behavior (craving and consuming substances that have no
nutritional value, such as ice, clay, soil, chalk, or paper)
has also been associated with iron-deficiency anemia, and
evaluation for pica behaviors should be routinely included
as part of the overall assessment.
Treatment Options for Iron-Deficiency Anemia in
CKD
It is important to diagnose iron deficiency in individuals
with CKD because treatment can readily correct the asso-
ciated anemia. Iron supplementation (either oral or intra-
venous) and/or ESA therapy are generally accepted as the
standard of care for iron-deficiency anemia in CKD
(correctable causes of anemia, such as iron deficiency,
should be addressed before ESA initiation).6,9,44-46 Iron
supplementation is recommended in CKD to treat iron
deficiency, prevent its development in ESA-treated in-
dividuals, and support ESA utilization and dosing for those
requiring ESA therapy. There are several types of oral iron
supplements available for the treatment of iron deficiency;
iron-only supplements are typically available in the form
of ferrous or ferric salts. Heme-iron preparations are a
newer type of oral iron supplement derived from bovine
hemoglobin that are also available,47 but dietitians should
be aware that these may not be suitable for vegans who
may only wish to take supplements from nonanimal
sources.
Guideline recommendations from KDIGO are summa-
rized in Fig 5. These include recommendations for iron
supplementation both with and without ESA therapy. Of
importance, evidence from clinical trials does not support
normalizing hemoglobin level with ESA treatment based
on reported worse outcomes compared with lower
targets, such as mortality and cardiovascular events.
Therefore, most guidelines recommend a hemoglobin
target range of 10-12 g/dL when treating with ESAs and
avoidance of hemoglobin concentrations >13 g/dL for all
adults.3,9,41 For iron supplementation with ESA therapy,
the KDIGO guidelines recommend that supplemental iron
Kidney Med Vol 5 | Iss 8 | August 2023 | 100677
should be administered to maintain serum ferritin
levels >200 ng/mL in individuals with CKD stage 5 treated
with hemodialysis and >100 ng/mL in those with NDD-
CKD stage 5 treated with peritoneal dialysis with TSAT
of >20% in all individuals with CKD.9 KDIGO guidelines
do not recommend routine use of iron supplementation in
patients with TSAT >30% or serum ferritin >500 ng/mL
(>500 mg/L).9 Since this 2012 guidelines, there has been
recognition that many individuals who are in an inflamed
state and exhibit a hepcidin-induced blockade to iron
may have altered iron metabolism that results in seemingly
high serum ferritin (eg, >500 ng/mL) but low TSAT
(eg, <15%), and thus, some guidelines suggest a maximum
serum ferritin level of 800 ng/mL.48,49 Currently, there is a
lack of consensus regarding the best parameters to estimate
body iron stores to guide treatment goals.40 Experts agree
that identifying these parameters is a high priority for future
research.40
When initiating treatment for iron deficiency, the
multidisciplinary care team can help advise individuals and
caregivers on the most appropriate iron formulation,
dosing, and administration schedule based on the patient’s
needs and dietary preferences and address other comor-
bidities that may be present. Pharmacists can help identify
issues related to polypharmacy and how that may affect
iron supplementation.50 Dietitians and nutritionists
become particularly important because most individuals
with CKD will require dietary modifications to maintain
optimal nutritional status, which usually requires re-
evaluation over the course of CKD.42,51 These members
of the care team can educate and support individuals with
strategies to minimize the GI side effects that can occur
with oral iron administration, while maximizing iron ab-
sorption.52 Guidance on adequate dietary fiber intake can
also improve gut motility, manage constipation, and pro-
mote overall gut health, which is an important consider-
ation for people with CKD in general.51 When folate and
vitamin B12 deficiency contribute to the development of
anemia in CKD, these vitamins can be replenished by diet
and/or supplementation.42 Dietitians involved in the care
of individuals with iron-deficiency anemia in CKD can
offer nutrition and diet counseling about good sources of
food rich in these nutrients53,54 and recommend supple-
mentation as appropriate.
Education in the Management of Iron-Deficiency
Anemia in CKD
Each member of the multidisciplinary care team plays a
vital role in educating individuals about anemia in CKD
and its management. It is important that family members,
care partners, or other supporters also receive education on
aspects of healthy kidney function, kidney disease, com-
mon comorbidities, and other potential complications of
CKD beyond anemia. Care partners and advocates should
be advised to monitor for these signs, symptoms, and risk
factors. Supporters should understand the basics of
7

nutrition and pharmacological regimens (including the
importance of taking medications as prescribed and po-
tential adverse events, such as GI upset with oral iron
supplementation) and the importance of physical
activity.49,55,56
Educational resources may include focused lectures,
pamphlets, and videos. Individuals with CKD can be
encouraged to become actively involved in their own care
and in shared decision-making by using regular telephone
or in-person touch points, adoption of technology-based
apps, and other self-management tools.51 The potential
benefits of patient education related to kidney function,
complications, treatment options, interventions, and life-
style are supported by findings from a trial of 297 par-
ticipants with CKD; the 149 participants who received
psychoeducational intervention showed a significantly
longer time to dialysis therapy compared with the 148
participants receiving usual care.57
In addition, involving patients and families in discus-
sions regarding goals of care can lead to positive health
outcomes, such as improved overall well-being and QoL. A
systematic review of 26 studies involving more than 5000
individuals with CKD found that the most effective
teaching sessions for improving individual outcomes were
those that included families and multidisciplinary teams.58
CONCLUSIONS
There is an ongoing opportunity to improve the man-
agement of iron-deficiency anemia in individuals with
CKD, a condition that is undertreated and associated with
increased mortality and reduced QoL. It is important to
diagnose iron deficiency in individuals with CKD because
treatment can readily correct the associated anemia. Iron
supplementation is widely used to manage iron-deficiency
anemia in CKD, and members of the multidisciplinary care
team should be aware of the specific considerations when
using this treatment. The multidisciplinary care team plays
a critical role in the care of individuals with iron-deficiency
anemia in CKD and has the potential to significantly
improve outcomes for those who are in their care.
ARTICLE INFORMATION
Authors’ Full Names and Academic Degrees: Debra Hain, PhD,
Donna Bednarski, MSN, Molly Cahill, MSN, Amy Dix, PhD, Bryce
Foote, PharmD, Mary S. Haras, PhD, Rory Pace, MPH, Orlando M.
Guti
errez, MD
Authors’ Affiliations: Florida Atlantic University, Boca Raton, FL
(DH); Detroit Medical Center Harper University Hospital, Detroit,
MI (DB); Kansas City Kidney Consultants, Kansas City, MO (MC);
Akebia Therapeutics Inc, Cambridge, MA (AD, BF); Georgetown
University School of Nursing, Washington, DC (MSH); Satellite
Healthcare, San Jose, CA (RP); University of Alabama at
Birmingham, Birmingham, AL (OMG).
Address for Correspondence: Debra Hain, PhD, Florida Atlantic
University, Christine E. Lynn College of Nursing, NU, Room 326,
777 Glades Road, Boca Raton, FL 33431. Email: dhain@health.
fau.edu
8 Kidney Med Vol 5 | Iss 8 | August 2023 | 100677
Hain et al
Support: Medical writing assistance was provided by Syneos Health
Medical Communications, LLC, and supported by Akebia
Therapeutics Inc.
Financial Disclosure: Debra Hain is a consultant for Akebia
Therapeutics Inc. Molly Cahill reports receiving funding from
Amgen and Eli Lilly. Amy Dix and Bryce Foote are employees of
Akebia Therapeutics Inc. Rory Pace reports receiving consulting
fees from Ardelyx, Nutricia, and Abbott. Orlando M. Guti errez
reports receiving grant funding and honoraria from Akebia and
Amgen, grant funding from GSK, honoraria from Ardelyx,
AstraZeneca, and Reata, and serving on a Data Monitoring
Committee for QED. The remaining authors declare that they have
no relevant financial interests.
Peer Review: Received October 31, 2022. Evaluated by 2 external
peer reviewers, with direct editorial input from an Associate Editor
and the Editor-in-Chief. Accepted in revised form April 1, 2023.
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