Iron Deficiency in

CKD Patients
 Anemia is a group of disease characterized by a decrease in either
hemoglobin (Hb) or circulating red blood cells (RBCs)
o Results in reduced oxygen-carrying capacity of the blood

 According to World Health Organization (WHO)

o ̴1.6 billion people (1/4 of world’s population ) are anemic

 Not an innocent bystander; affects both length and quality of life

(QOL)

 IDA occurs across all populations and is associated with

o Diminished QOL
o Physical and cognitive performance, and
o Unfavorable clinical outcomes

http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf
 Anemia

Macrocytic Normocytic Microcytic

Megaloblastic Non-megaloblastic IDA Genetic

Anomaly
1. Hepatic disease
1. Vitamin B12 2. Drug-induced
1. Recent blood loss 1. Sickle cell
deficiency anemia
2. Hemolysis 2. Thalassemia
2. Folic acid 3. Hypothyroidi
deficiency sm 3. Bone marrow failure
4. Reticulocytosi 4. Anemia of chronic disease
s

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

 According to WHO
o Anemia is defined as Hb <130 g/L in men or <120 g/L in female

 IDA is the result of long-term negative iron balances

o Progressive loss of iron stores in the form of hemosiderin and ferritin

 IDA is defined as
o Anemia with biochemical evidence of iron deficiency based on
following laboratory findings
• Serum ferritin, total iron binding capacity (TIBC), transferrin saturation, or
transferrin receptor

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

  IDA is the most common nutritional deficiency in developing and
developed countries

 IDA is considered to be the leading cause of anemia worldwide,

accounting for as many as 50% of cases

 Prevalence of IDA greatly varies according to age, gender,

physiological, pathological, environmental, and socioeconomic
conditions

 Data from NHANES*, prevalence of IDA

o Young children 1.2%
o Women of childbearing age 4.5%

*National Health and Nutrition Examination Survey http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf

Initial ̶ Iron stores are reduced without reducing serum iron levels and can
be assessed with serum ferritin measurement
Stage ̶ Iron stores can be depleted without causing anemia
Once iron stores are depleted, there still is adequate iron from daily RBC turnover
for Hb synthesis
Second
Iron deficiency occurs; Hb falls just above the lower limit normal
Stage

Third Considered as IDA and occurs because of Hb falls to less than normal values

Stage
 IDA results from prolonged negative iron balance

 Mainly due to following factors:

1. Inadequate iron intake

2. Decreased iron absorption

3. Increased iron demand or hematopoiesis

4. Increased iron loss

Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
Females in the reproductive period of life
Menstruation
Pregnancy
Pathological blood loss
Deficient diet
Adult males and postmenopausal females
Pathological blood loss
Infants and children
Deficient diet
Diminished iron stores at birth

Etiology Firkin F. Hypochromic anemia. In: de Gruchy’s Clinical Hematology in Medical Practice, 1989
 Iron deficiency anaemia in CKD

• Blood loss from GI tract

• In HD patients : Repeated Blood Loss ; retention of Blood in

Dialyzer and blood lines.

• Frequent Blood Sampling for Ix

• Loss from Surgical Procedures ( vascular access)

• Interference with absorption due to Meds ( Gastric acid

inhibitors ,Phosphate Binders )

• Reduced absorption due to inflammation

CKD stage and anaemia prevalence
 What causes anemia in CKD ?

• Relative Erythropoietin (EPO) deficiency

• Iron deficiency
• Blood loss
• Shortened red cell life span
• Vitamin deficiencies
• The “uremic milieu” /Bone marrow suppression
• Inflammation
• Hyperparathyroidism
Mechanisms underlying anaemia in CKD
 IDA Prognosis

 IDA adversely effects

o Cognitive performance, behavior, and physical growth of infants,

preschool, and school-aged children

o The immune status and morbidity from infections of all age groups

o The use of energy sources by muscle and thus the physical capacity and
work performance of adolescents and adults of all age groups

o Increase perinatal risks for mothers and neonates and overall infant
mortality during pregnancy

http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf
 
Chief Complaints
Fatigue, lassitude, palpitation, and generalized weakness
History
Chronic blood loss, deficient diet
Clinical Features
1. Palor skin, nailbed, conjunctiva
2. Koilonychia (brittle, spoon shaped nails)
3. Atrophic glossitis (atrophy of tongue papilla; making the tongue
smooth and shiny)
4. Pica (compulsive eating of nonfood items) or pagophagia
(compulsive eating of ice)
Firkin F. Hypochromic anemia. In: de Gruchy’s Clinical Hematology in Medical Practice, 1989
 Symptoms Signs
Decreased exercise tolerance Tachycardia
Pale appearance (most prominent in
Fatigue conjunctiva)
Dizziness Decreased mental acuity
Increased intensity of some cardiac valvular
Irritability murmurs
Weakness
Palpitations
Vertigo
Shortness of breath
Chest pain
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Complete blood count (CBC), erythrocyte sedimentation rate
(ESR), and peripheral blood film (PBF)

 Serum Iron profile

 Bone marrow study (if needed)

 Investigations to determine other causes of IDA (e.g. fecal

occult blood test, colonoscopy, urine examination)
 Hematologic Indices Normal Range IDA
Hb 70—160 g/L Low
Hematocrit (Hct) 0.320—0.47 L/L Low
Mean corpuscular volume (MCV) 75—95 fL Low
Mean corpuscular hemoglobin (MCH) 24—30 pg Low
Mean corpuscular hemoglobin
concentration (MCHC) 290—370 g/L Low

Red cell distribution width (RDW) 11—15% High (early)

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011c

Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
 
 Short term
o Resolution of symptoms
o Replenish iron stores

 Long term
o Improve quality of life (QOL)
o Prevention of recurrences
o Better growth and development (children)
 Pharmacological management
o Oral/parenteral iron therapy

 Non-pharmacological
o Blood transfusion
 Decision to manage anemia is based on the evaluation of risk and
benefit

 Transfusion is generally not indicated if Hb >100 g/L whereas

transfusion of RBCs should be considered when Hb is <70 to 80 g/L
in hospitalized, stable patient

 Transfusion of allogeneic blood is indicated in acute situations (e.g.

severe blood loss)

 Transfusions may also be necessary for patient with cardiac

instability
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiolog ical Approach, 2011
KFSH&RC Transfusion Guideline: http://ig.kfshrc.edu.sa/wps/portal/
Szczepiorkowski Z. et al. ASH Education Book 2013;1:638 -644 or
http://asheducationbook.hematologylibrary.org/content/2013/1/638.full
Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
 Recommended dosage requirements
o 200 mg elemental iron per day for 3-6 months
o 2-3 divided doses to maximize tolerability
o Administration should be 1 hour before meals or on empty
stomach

 Absorption of all oral preparations are similar

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

http://www.pharmapacks.com/product_images/g/220/a1174335_2761 43287.jpg
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Gastrointestinal (GI) intolerance
o Nausea, vomiting, heartburn, and diarrhea or constipation
o Slow release or sustained release preparations may be used
o Combination products, e.g. Ferro-DDS (ferrous fumarate/docusate),
may be advantageous for certain patient population

 Cause discoloration of stool

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Indications for therapy
o Intolerance to oral route
o Malabsorption
o Long-term nonadherence
o Patient with significant blood loss who refuse transfusion and are
intolerant to oral therapy
o Chronic kidney disease (CKD)

 Currently available formulations include

o Dextran, sodium ferric gluconate, iron sucrose, and ferumoxytol

 Formulations differ in their molecular size, degradation

kinetics,
bioavailability, and side effects profile

 All preparations carry a risk for anaphylactic reactions but likely

to a lesser extent than iron dextran
 Amount of
elemental
Formulation iron Warning Treatment Common adverse effects
(mg/mL)

Black Box Pain and brown staining

Iron Dextran Warning (BBW): 10 doses x 100 mg at injection site, flushing,
(INFeD) 50 anaphylactic type = 1,000 mg hypotension, fever, chills,
reactions myalgia, anaphylaxis

Sodium Ferric No BBW: Cramps, nausea and

Gluconate Hypersensitivity 8 doses x 125 mg = vomiting, flushing,
62.5 1,000 mg
(Ferrlecit) reaction hypotension, rash, pruritis

BBW: Leg cramps, hypotension

Iron Sucrose* anaphylactic type
(Ferosac®) Up to 10 doses x
20 reactions 100 mg = 1,000 mg

No BBW: Diarrhea, constipation,

Ferumoxytol Hypersensitivity 2 doses x 510 mg = dizziness,
(Feraheme) 30 1,020 mg
reaction hypotension,
peripheral edema
*KFSH&RC Formulary DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Total iron deficiency in mg =
Hb-iron deficiency + depot iron

Hb-iron deficiency (in mg) = body weight (kg) x (normal Hb - actual Hb in g/L) x 0.24 §

Above calculation is based on:

 A normal Hb 150 g/L for body weights >35 kg and 130 g/L ≤34 kg body weight
respectively
 The iron-content of hemoglobin (0.34%)
 The blood volume (∼7% of the body weight) and the requirements of depot
iron
(∼15 mg/kg up to a weight of about 34 kg, total of 500 mg >34 kg)
 §Factor 0.24 = 0.0034 x 0.07 x 1000

KFSH&RC Formulary
*Iron sucrose
http://online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/289383
Intravenous Versus Oral Iron in CKD

• Tilman B. Drüeke. Oral or intravenous iron for anaemia correction in chronic kidney disease?. Kidney International (2015)
 Liposomal Iron

• Liposomes are effective drug carrier systems with

potential for target specific delivery of different
therapeutic substances.

• Their biocompatibility, biodegradability and low

toxicity make them a suitable option for
delivering drugs.

• Liposomal iron is a new generation oral iron

preparation of ferric pyrophosphate carried
within a phospholipid and lecithin membrane,
where iron is directly absorbed in the intestine
and does not come in contact with the GI mucosa.

• Liposomal iron has a high bioavailability with

lower incidence of side effects.
Advantages of Liposomal Iron
 Liposomal formulation facilitates quicker
absorption & availability of iron in the body

Journal of Biosciences and Medicines 2020; 8: 27-41

Absorption and bioavailability of liposomal
formulation
Liposomal iron is 2.7 and 3.5 times more bioavailable than
ferrous Sulphate & ferric pyrophosphate

Liposomal
Iron

Journal of Biosciences and Medicines 2020; 8: 27-41

Liposomal iron – Better tolerated than other iron
formulations

Journal of Biosciences and Medicines 2020; 8: 27-41

 Oral liposomal iron safe & efficacious in managing CKD
patients with anaemia

Haemoglobin (Hb), hematocrit (Ht), and ferritin level before and after 6 months of liposomal iron treatment
(T0: Before treatment; T1: 6 months after treatment)

Exp Rev Hematol 2016;9(Suppl 1):1-42

In this randomized, open-label trial, 99 patients with
CKD (stage 3–5, not on dialysis) and iron deficiency
anaemia [haemoglobin (Hb) ≤12 g/dL, were assigned
(2:1) to receive oral liposomal iron (30 mg/day) or a
total dose of 1000 mg of IV iron (125 mg infused
weekly) for 3 months

Nephrol Dial Transplant (2015) 30: 645–652

 The short-term therapy with IV iron
produced a more rapid Hb increase
compared with liposomal iron

The final increase in Hb was similar with

either treatment

Results The difference between the groups was

statistically significant at the first month
and such difference disappeared at the end
of treatment

The incidence of adverse event was

significantly lower in the oral group (P <
0.001)

Nephrol Dial Transplant (2015) 30: 645–652

Lower incidence of adverse events with Liposomal Iron as
compared to IV Iron

Liposomal Iron IV Iron

Nephrol Dial Transplant (2015) 30: 645–652

 Oral liposomal iron is not inferior to IV iron
to correct anaemia in NDCKD patients,
although its ability to replete iron storage
sites and to maintain raised Hb values after
drug withdrawal remains lower than the IV
administration.

Oral liposomal iron is a safe and efficacious

alternative to IV iron to correct anaemia in
Conclusion ND-CKD patients.

The low rate of adverse events with

liposomal iron, its practicality and the
globally lower cost of oral therapy suggest
that this formulation may represent the first
step to correct anaemia in uncomplicated
CKD patients

Nephrol Dial Transplant (2015) 30: 645–652

 Summary
• Iron deficiency anaemia is common in women, children and adolescents and in certain
chronic diseases like CKD, CHF, IBD, cancer.

• Iron supplementation is fundamental in the management of several conditions leading to

iron deficiency anaemia.

• Oral iron preparations have poor tolerability leading to non-compliance, and IV

preparations need to be administered carefully to avoid anaphylactic reactions.

• Parenteral therapy is usually not indicated unless patient is intolerant to oral therapy,
having malabsorption, or in the case of CKD

• Liposomal iron is new generation oral iron preparation of ferric pyrophosphate carried
within a phospholipid and lecithin membrane, where iron is directly absorbed in the
intestine

• Liposomal iron has a high bioavailability with lower incidence of side effects

• Liposomal iron is better tolerated than IV and oral iron

 Summary

• Oral liposomal iron is non-inferior to IV iron to correct anaemia in NDCKD patients.

• In patients with CKD, administration of liposomal iron results in improvement in Hb values

across the CKD spectrum and in patients on dialysis.

• Oral liposomal iron is a safe and efficacious alternative to IV iron to correct anaemia in
ND-CKD patients.

• Use of liposomal iron has been shown to improve the QoL.

• Liposomal iron could be considered as an alternative for the treatment of iron deficiency
anaemia in those patients who do not tolerate classic prepared doses of oral iron.