This document provides an overview of the management of anemia in chronic kidney disease. It defines anemia according to WHO criteria and notes that nearly 90% of CKD patients with a GFR below 30 mL/min have anemia. The main causes of anemia in CKD are decreased erythropoietin production and a shorter red blood cell lifespan. Treatment with erythropoiesis-stimulating agents or ESAs like epoetin and darbepoetin can help increase hemoglobin levels and improve outcomes. The goals of ESA therapy are to raise hemoglobin by 1-2 g/dL per month until it reaches 10-11.5 g/dL without exceeding 13 g/dL. Iron supplementation is

1. Management Of Anemia
In Chronic Kidney
Disease
Presented By:
Boushra M. Alsaor
[Pharm D intern]
Al Maaefa college

2. Definition
 Anemia has been defined by the World Health
Organization (WHO) as a hemoglobin (Hgb) concentration:
 <13.0 g/dL for adult males and postmenopausal women
 <12.0 g/dL for premenopausal women .

3. Prevalence
 Based upon these criteria, nearly 90 percent of patients
with a glomerular filtration rate (GFR) <25 to 30 mL/min
have anemia, many with Hgb levels <10 g/dL.

4. Several factors are responsible for anemia in CKD
 Decreased erythropoietin production (most important).
 Shorter life span of RBCs.
 Blood loss during dialysis.
 Iron deficiency.
 Anemia of chronic disease.
 Renal osteodystrophy.

5. Treatment of anemia in CKD can
 Decrease morbidity/mortality.
 Reduce left ventricular hypertrophy.
 Increase exercise tolerance.
 Increase quality of life.

6. Anemia work-up
 Initiate evaluation when CrCl is less than 60 mL/minute or
hemoglobin is less than 11 g/dL.
 Hemoglobin/hematocrit.
 Mean corpuscular volume.
 Reticulocyte count.
 Iron studies:
 Transferrin saturation (total iron/total iron-binding capacity)—Assesses available
iron.
 Ferritin—Measures stored iron.
 Stool guaiac.

7. Treatment options
 Iron.
 Erythropoietin stimulating agent(ESA).
 Blood transfusion.
 Folic acid and vitamin B12.

8. Erythropoiesis-stimulating agents (ESAs)
 Epoetin-α
 Same molecular structure as human erythropoietin (recombinant DNA
technology).
 Binds to and activates erythropoietin receptor.
 Administered either SC or IV.
 Darbepoetin-α
 Molecular structure of human erythropoietin has been modified from 3 N-
linked carbohydrate chains to 5 N-linked carbohydrate chains; increased
duration of activity. The advantage is less-frequent dosing.
 Binds to and activates erythropoietin receptor.

9. When to start ESA and Hemoglobin goal
 Risk vs benefit.
 Address all correctable causes of anemia (including iron deficiency and
inflammatory states) prior to initiation of ESA therapy.
 In non dialysis Patients:
 Consider starting ESA treatment only when the Hgb level is <10 g/dL and reduce or
stop the ESA dose if the Hgb level exceeds 10 g/dL.
 For patients on dialysis:
 Initiate ESA treatment when the Hgb level is <10 g/dL and reduce or interrupt the ESA
dose if the Hgb level approaches or exceeds 11 g/dL
 Try to maintain goal Hgb levels between( 10.0 and 11.5 g/dL). Avoid
hemoglobin concentration greater than 13 g/dL.

10. Dosing
 Epoetin-alfa or epoetin-beta dosing usually starts at:
 20 to 50 IU/kg body weight three times a week.
 Darbepoetin-alfa dosing usually starts at:
 0.45 mg/kg body weight once weekly by SC or IV administration.
 0.75 mg/kg body weight once every 2 weeks by SC administration.
 In patients with a history of CVD, thrombo-embolism or seizures, or
in those with high blood pressure, the initial doses should be in the
lower range.

11.  The objective of initial ESA therapy is a rate of increase in Hb
Concentrations of 1.0 to 2.0 g/dl (10 to 20 g/l) per month.
 The rise in Hb of greater than 2.0 g/dl (20 g/l) over a 4-week period
should be avoided.
 Rapid rising of Hgh can induce hypertension and seizures.
Hemoglobin raising with ESA:

12. Dosing adjustment
 Epoetin-alfa or epoetin-beta dosage may subsequently be increased
every 4 weeks by a weekly dose of 320 IU/kg if the increase of Hb is
not adequate.
 Increases in dose should not be made more frequently than once a
month. If the Hb is increasing and approaching 11.5 g/dl (115 g/l), the
dose should be reduced by approximately 25%.
 If the Hb continues to increase, doses should be temporarily withheld
until the Hb begins to decrease, at which point therapy should be
reinitiated at a dose approximately 25% below the previous dose.

13. Adjuvant Therapies
 KDOQI guideline recommend not using androgens as an adjuvant
to ESA treatment.
 Also suggest not using adjuvants to ESA treatment including
vitamin C, vitamin D, vitamin E, folic acid, L-carnitine, and
pentoxifylline.

14. ESA Monitoring
1. Hemoglobin concentrations initially every 1–2 weeks and then every
2–4 weeks when stable.
2. Monitor BP because it may rise (treat as necessary).
3. Iron stores:
A. Ferritin: HD target is 200–500, and peritoneal dialysis/CKD target is
100–500.
B. Transferrin saturation target is greater than 20% (upper limit of 50%
removed from recent guidelines).

15. Common causes of inadequate response to ESA therapy
1. Iron deficiency is the most common cause of erythropoietin
resistance.
2. Infection and inflammation.
3. Other causes: chronic blood loss, renal bone disease, aluminum
toxicity, folate or vitamin B12 deficiency, malignancies,
malnutrition, hemolysis, and vitamin C deficiency.

16. Risk of ESA
 Higher chance of death was reported and an increased number of blood
clots, strokes, heart failure, and heart attacks was reported in patients with
chronic kidney failure when ESAs were given to maintain hemoglobin levels
of more than 12 grams per deciliter.
 Higher chance of death and an increased rate of tumor growth were
reported in patients with advanced head and neck cancer receiving radiation
therapy and in patients with metastatic breast cancer receiving
chemotherapy, when ESAs were given to maintain hemoglobin levels of
more than 12 grams per deciliter.
 Higher chance of death was reported and no fewer blood transfusions were
received when ESAs were given to patients with cancer and anemia not
receiving chemotherapy.
 Higher chance of blood clots was reported in patients who were scheduled
for major surgery and given ESAs.

17. Iron Therapy
 Iron therapy is important to replete iron store.
 Parenteral iron therapy improves response to ESA and reduce the
dose required to achieve and maintain target indices.

18. Parenteral VS oral iron therapy
 Parenteral therapy is the recommended route for all CKD patients.
 Most patients with CKD who are receiving erythropoietin therapy
require parenteral iron therapy to meet needs (increased
requirements, decreased oral absorption).
 Oral therapy is limited by poor absorption and non adherence with
therapy due to adverse effects.
 Consider oral supplemental iron in ND or PD patient without IV access
or as maintenance therapy for ND or PD patients.
 Oral route is not recommended in HD patients.

19. Iron Therapy:
 Oral: 200mg elemental iron per day (= 600 mg Ferrous fumarate,1.8g ferrus
gluconate or 1gm ferrous sulphate ).
 Parenteral:

20. Adverse effects of iron therapy
 Allergic reaction.
 Hypotension.
 Dizziness.
 Dyspnea.
 Headache.
 Low back pain.
 Arthralgia.
 Syncope.
 Arthritis.
Some side effects can be reduced by decreasing the dose or rate of infusion.
Sodium ferric gluconate or iron sucrose has better safety profile than iron dextran.

21. Red blood cell transfusion
 ESA therapy is ineffective (e.g., hemoglobinopathies, bone marrow
failure, ESA resistance).
 The risks of ESA therapy may outweigh its benefits (e.g., previous or
current malignancy, previous stroke).
 When rapid correction of anemia is required to stabilize the patient’s
condition (e.g., acute hemorrhage, unstable coronary artery disease).
 When rapid pre-operative Hb correction is required.
 Transfusion should be directed toward reduction of anemia sign and
symptoms rather than achieving specific target.

22. Q & A
Thanks For Your Attention …