This document discusses the management of anemia in chronic kidney disease (CKD). It begins by defining anemia and its causes in CKD, which include reduced erythropoietin production and decreased red blood cell survival due to kidney failure. Left untreated, anemia in CKD can lead to deterioration in cardiac function, impaired cognition, and increased fatigue and mortality risk. The main therapeutic options for treating anemia in CKD are red blood cell transfusions, androgens, and erythropoiesis-stimulating agents (ESAs). ESAs such as epoetin alfa and darbepoetin alfa are now the standard treatment as they reduce transfusion needs and risks while helping to mobilize

1. ANEMIA IN CKD- HOW TO
MANAGE IT
7/7/2015 1

2. TOPICS BEING DISCUSSED
Anemia in CKD
Causes for Anemia in CKD
Reasons for Anemia correction
Therapeutic options for correction in anemia of
CKD
7/7/2015 2

3. ANEMIA IN CKD
• Anemia - WHO recommendations- Hb concentration
<13.0 g/dL for adult males and postmenopausal
women and an Hb <12.0 g/dL for premenopausal
women
• The anemia of chronic kidney disease
(CKD)normocytic and normochromic
7/7/2015 3

4. Causes for Anemia in CKD
• Failure of Erythropoietin (EPO) production by
diseased kidney
• Reduction in red cell survival
7/7/2015 4

5. 7/7/2015 5

6. Reasons for Anemia Correction
• Deterioration in cardiac function
• Decreased cognition and mental acuity
• Fatigue
• Increased risk of morbidity and mortality
7/7/2015 6

7. THERAPEUTIC OPTIONS FOR CORRECTION IN ANEMIA
OF CKD
RED BLOOD CELL
TRANSFUSIONS
ERYTHROPOIETIN-
STIMULATING AGENTS (ESAS)
ANDROGENS
7/7/2015 7

8. RBC TRANSFUSIONS
• Universally successful in increasing Hb levels.
• Decreases symptoms & improve health-related
quality of life.
• COMPLICATIONS
Transfusion-transmitted infection
Immunologic sensitization
Iron overload syndromes
Volume overload
Transfusion reactions
7/7/2015 8

9. Androgens
• Androgens (se endogenous EPO production,
sensitivity of erythroid progenitors to the effects of
EPO, and red blood cell survival) were used regularly
in the treatment of anemia in dialysis patients.
• Limited role side effects – IM injection, acne,
priapism, hepatitis, LFT abnormalities, and risk of
HCC.
7/7/2015 9

10. ERYTHROPOIETIN-STIMULATING AGENTS (ESAS)
• Initial phase III clinical trial showing that recombinant human EPO
was effective and eliminated the need for continued transfusions.
• In this study, 333 dialysis patients with Hb levels <10 g/dL received
recombinant human EPO to maintain the hematocrit at 35 % .
• Within 2 months of initiation of therapy, the need for transfusions
(1030 within the six months prior to beginning treatment) was
eliminated.
• In addition, there was a 40 % reduction in ferritin levels after 6
months among the 68 patients with iron overload.
7/7/2015 10

11. • They substantially reduced the need for red cell
transfusions
• Decrease in risk for transfusion-related complications
• They also help mobilize iron stores, which is
particularly beneficial in patients with CKD and iron
overload due to previous transfusions
7/7/2015 11

12. PEGINESATIDE
• Peginesatide is a synthetic peptide that activates the
EPO receptor
• Stimulates erythroid colony growth, reticulocyte
count, and hematocrit
• Does not crossreact with EPO antibodies (amino acid
sequence is unrelated to EPO)
7/7/2015 12

13. 7/7/2015 13

14. • In 2 phase-III studies (PEARL-I and PEARL-II) that compared
peginesatide with darbepoetin among non-dialysis CKD
patients, there was an increase in cardiovascular events
associated with peginesatide.
• FDA approved peginesatide for IV or SC administration to
treat anemia in adult dialysis patients only, but not in patients
with CKD who are not on dialysis or in patients with cancer-
related anemia.
• Serious hypersensitivity reactions reported in approximately
0.2 % of patients following the first dose of IV administration,
with death occurring in 0.02 % of patients
7/7/2015 14

15. Darbepoetin alfa
• Used for the treatment of anemia of CKD
• It is a molecule with 165 amino acids that differs from
recombinant human EPO in that it contains five N-linked
oligosaccharide chains, whereas EPO has only three
• The additional carbohydrate chains result in a half-life that is
longer than that for EPO
7/7/2015 15

16. PRINCIPLES GOVERNING THE ADMINISTRATION OF
RECOMBINANT HUMAN ESAS
• The response to EPO is dose-dependent
• The response is dependent on the route of administration (IV
Vs. SC ) and the frequency of administration.
• The response may be limited by low iron stores, bone marrow
fibrosis, infection, inflammation, inadequate dialysis, and
other conditions.
• Stroke, mortality, and hypertension may complicate therapy.
This is primarily limited to patients undergoing dialysis.
7/7/2015 16

17. INDICATIONS OF ESA
• Use in HD patients – Hb level of <10g/dL with consideration
specific patient characteristics, such as functional and
cognitive status, life-expectancy
• Nondialysis patients with CKD- initiate ESAs when Hb levels
are <10 g/dL and try to maintain goal Hb levels between 10.0
and 11.5 g/dL.
• Exceptions- Dialysis patients who have a H/o stroke or
malignancy, or an active malignancy.
• ESAs should not be started until iron status has been
evaluated
7/7/2015 17

18. • Reliance upon the hematocrit alone is not the optimal
method for assessing the response to ESAs
• Laboratory variability in the measurement of hematocrit is
greater than for Hb
• Current Guidelines- Recommend the use of Hb rather than
hematocrit, for evaluating & treating anemia in CKD patients
• Route of administration
• Large studies – SC dose of EPO required to achieve a target
Hb is approximately 30 % less than that required with IV
administration.
7/7/2015 18

19. 7/7/2015 19

20. • The 2012 KDIGO guidelines suggest either IV or SC
administration for patients on hemodialysis,
hemofiltration, or hemodiafiltration, and SC
administration for nondialysis CKD patients or
patients on peritoneal dialysis
7/7/2015 20

21. Dose
• Initial dose of EPO baseline Hb level, overall clinical setting,
mode of administration & target hemoglobin level
• Numerous studies  IV therapy requires 30% more EPO than
with the subcutaneous route
• The FDA-recommended starting dose is 50 to
100 units/kg three times per week for both IV and
subcutaneous administration
7/7/2015 21

22. Side effects
• Hypertension
• Headache
• Pure red cell aplasia
• Hyporesponsiveness to ESAs
 No increase in Hb concentration after 1st month of
appropriate weight-based dosing & acquired
hyporesponsiveness as requiring two increases in ESA doses
up to 50% beyond the dose at which the patient had
originally been stable- KDIGO
7/7/2015 22

23. Causes for resistance to ESA
• Absolute iron deficiency  external blood
losses or exhaustion of iron stores due to an increase in
erythropoiesis caused by ESA treatment
• Bone disease due to secondary hyperparathyroidism
• Occult malignancy and unsuspected hematologic disorders
• Multiple myeloma/myelofibrosis/myelodysplastic syndrome
• HIV infection
• Chronic inflammation (with inhibition possibly due to
enhanced cytokine production)
7/7/2015 23

24. THANK YOU
7/7/2015 24