Anemia in CKD

Question 1

What’s the definition of Anemia in CKD?

Answer 1

Hemoglobin below 13g/dl in males and 12 in females

Question 2

What are the goals of anemia treatment in CKD (there’s 4 listed)?

Answer 2

• Increase O2 carrying capacity (HGB)
• Increase QOL of patients
• Prevent/alleviate symptoms
• Decrease the need for blood Transfusions–> More transfusions=more risk of kidney transplant rejection!
• —–NONE OF THE TREATMENTS DECREASE MORTALITY!!!

Question 3

What things are needed to make hemoglobin specifically?

Answer 3

Iron, Folate, and B12

Question 4

Characteristics of anemia in CKD and it’s types

Answer 4

RBC lifespan is shorter and it normally occurs once GFR starts going below 45.
its usually normochromic and normocytic anemia, microcytic anemia is rare

Question 5

What is the baseline anemia Lab assessment markers and target recomendations in CKD?
*Note, HGB is the best marker of O2 capacity of the blood

Answer 5

RBC count: WNL (cells/ul)
Hemoglobin: 10-11g/dl
Hematiocrit: 30-33%
Mean Cell Volume: WNL (fL/cell)
Reticulocyte count: x>2.5%
Serum Iron (iron bound to transferrin): WNL (ug/dl)
Serum Ferritin (Storage form of iron): basically >500ng/ml per KDIGO
TIBC: WNL (ug/dl)
Tsat: >20% per KDOQI but >30% per KDIGO

Question 6

What’s the most common cause of ESA resistance and what do you need to address before starting an ESA?

Answer 6

Iron is the most common cause of ESA resistance and it must be corrected 1st before starting an ESA–> It should be monitored q3 months for ESRD patients and anyone receiving Epo for anemia

Question 7

What’s the timeframe for responding to iron?

Answer 7

Reticulocytes increase in 7-14 days and HGB/HCT in 3-4 weeks

Question 8

Lab Goals of Iron Therapy?

Answer 8

Tsat>30% and Ferritin>500ng/ml
(Hold IV iron if TSAT>50% or ferritin>1200ng/ml……. if ferritin is 1200-2000, only use iron IF: Tsat is well below 30 and there are clinically relevant sx of anemia, HGB<10 or still EPO resistant

Question 9

Characteristics of oral Iron therapy

Answer 9

POOR absorption (~10% bioavailable) and POOR adherence (<50%), GI complications: nausea, constipation, and it is a SLOW replenishment of iron stores- but it’s cheap

Question 10

Characteristics of Parenteral Iron

Answer 10

Expensive! But: Better absorption, rapid replenishment of iron stores but there’s risk of iron overload, infusion reactions, anaphylactic reactions, and you want to AVOID IM IRON- its painful!
-Also IV Iron can worsen infections, it helps bacteria grow!

Question 11

AE’s of oral iron

Answer 11

Gi Upset (Nausea,cramping,constipation)
Dark Stool (it's makes it look like there might have benn blood in it because it's darkened but it's the iron)
GI iron has many DDI's (ie with calcium carbonate)

Question 12

AE’s of IV Iron

Answer 12

Dyspnea/wheezing, itching, myalgias

• Hypotension, flushing, edema
• chest pain and cardiac arrest
• Injection site rxns–> anaphylactic and anaphylactoid reactions
• INFECTION

Question 13

What’s the daily target dose of Iron?

• Ferrous Sulfate is __% elemental iron so it’s dosing is….
• Ferrous Fumarate is __% elemental iron so it’s dosing is….
• Ferrous Gluconate is __% elemental iron so it’s dosing is….
• -Polysaccharide iron is __% elemental iron so it’s dosing is….
• -Ferric Citrate is __% elemental iron so it’s dosing is….

Answer 13

Around 200mg of Elemental Iron per day… remember iron is only ~10-15% bioavailable so they’re only replenishing about 20mg of iron each day
Ferrous Sulfate is 20% iron so it’s 325 (65mg iron) TID or 195(39) pills as well and 525 (105) in the ER form
-Ferrous fumarate is 33% Iron so 325(107) BID or 195(64) TID
-Ferrous Gluconate is 12% iron so 325(39)
-Polysaccharide iron and ferric citrate/auryxia are both 100% iron
—All forms EXCEPT ferric citrate/auryxia have an elixir form

Question 14

Should you use every other day dosing to incrase iron’s bioavailability in CKD patients?

Answer 14

This hasn’t been studied in CKD patients, GI side effects and compliance may be better and they may absorb more with each dose but they’re getting less iron overall too so don’t do this with most CKD patients.
-ONLY USE IN very mild cases of anemia

Question 15

Drugs that decrease oral iron’s absorption (Iron needs acid to be absorbed better):

Answer 15

Al, Mg, & Calcium antacids, Tetracyclines, H2 antagonists, PPIs, cholestyramine

Question 16

Drugs whose absorption is affected by iron?

Answer 16

Fluoroquinolones, Levothyroxine, Tetracyclines, Mycophenolate, methyldopa, levodopa

Question 17

Most common IV Iron Formulations and their dosing

Answer 17

Ferric Gluconate/Ferrocrit: 125mg IV TIW x8 doses
Iron Sucrose/venofer: 100mg IV 1-3x/week for 1 gram total
The above two are the most common and the ones below are more expensive but may be better for clinics since it’s not as many doses/shorter duration
Ferumoxytol: 510mg IV x2 doses, 3-8 days apart
Ferric Carboxymaltose: 750mg IV x2, 7 days apart

Question 18

IV iron pearls

Answer 18

IV is preferred in HD because they have an increased need and often are on epo.

• In NON-HD patients, if not too severe, can do a 1-3month trial of PO iron and if that doesn’t work then move to IV
• AVOID IV iron in patients with ACTIVE INFECTION

Question 19

What are the 4 different ESAs and their Frequency of administration?

Answer 19

1.) Epoetin alfa (Epogen)
-HD patients: TIW IV
-Non-HD patients: 1x/week SQ
–***Epogen can be given IV or SQ with SQ using
20% less (HD patients still usually get IV)
2.) Darbepoetin Alfa/Aranesp (PEGylated form of Epogen):
-IV or SQ, Once weekly –> Can be given Once every other week (PEGylated so lasts longer in body)
– Dosing conversion from Epogen is 200Units Epo:1
mcg darbepoetin
3.) Mircera/Epoetin Beta: **Longest Lsting!
-IV or SQ every 2 weeks–> up to Once every 4 weeks
—This drug’s different, it’s a EPO receptor agonist
4.) Epoetin alfa epbx (Retacrit) is just a biosimilar to Epogen, same dosing and stuff but 33% cheaper

Question 20

What’s the initial/listed dosing and timing of the different esa’s?

Answer 20

1. ) Epo-a/Epogen:
   - Dialysis patients: 50-100 Units/kg TIW
   - Non-Dialysis patients: 50-100U/kg SQ QW
2. ) Aranesp/Darbepoetin-alfa: 0.45ug/kg IV/SQ QW
3. ) Epoeitin-beta/Mircera: 0.6mcg/kg IV/SQ every 2 weeks
4. ) Retacrit: Same as Epo-a/Epogen

Question 21

HGB cutoffs in HD and non HD patients getting ESA’s:

Answer 21

Going by the FDA guidlines:
-Non-Dialysis patients/ND-CKD: Basically PRN when
HGB falls below 10g/dL –> Give ESA when HGB gets
below 10 and stop giving it when HGB gets above 10

ESRD/Dialysis patients: Initiate ESA when HGB<10g/dL and treat to 10-11g/dL
-For dialysis patients, 11g/dl is the upper limit- no give
ESA if HGB goes above 11 (or is heavily trending that
it will exceed 11 soon)

**Main idea is to avoid blood transfusions while not letting HGB get too high because that can cause issues

Question 22

How/how often are ESA doses changed?

Answer 22

ESA dose changes are only done every 4 weeks or longer and if needed, doses are simply increased or decreased by 25%
- Only every 4 weeks and by +/- 25% if needed.

Question 23

ESA target HGB changes and when to increase/reduce the dose:

Answer 23

Goal is 1-2g/dl per month increase in HGB
Increasing: Increase dose by 25% if patient is below target after 4 weeks
-Decreasing dose:
–If HGB Increases by more than 1g/dl in 2 weeks (or more than 0.5g/dl in a week), reduce the dose by 25%.
– Reduce ESA dose by 25% as patient’s HGB approaches 11g/dl

Question 24

Common causes of ESA Resistance:

Answer 24

#1: IRON DEFICIENCY
Then: ACEi's, Hyperparathyroidism, Aluminum toxicity, folate and or B12 deficiency, infection, malignancy, trauma, inflammation

Question 25

What are the AE’s of ESAs:

Answer 25

HYPERTENSION- this is dose dependent,
  --HOLD ESA DOSE IF: BP> 200/100
Hypercoagulability--> Increased risk of thrombosis, 
     DVT, PE, CVA etc
Hypersensitivity Reactions
Pure red blood cell aplasia (PRBCA): Rare but very bad
Headache, fatigue, edema
Progression of malignancy

Question 26

What to do with ESA’s in malignancy?

Answer 26

If there’s anticipation of a cure then ESA use is CONTRAINDICATED!
-If not, it’s a discussion with the patient–> It may imporve QOL but decrease lifespan

Question 27

Black box warning for ESA’s

Answer 27

Do not exceed HGB of 11g/dl due to increased risk for death and serious CV/stroke risk
-Use lowest dose needed to decrease the need for blood transfusions

Question 28

What are the ESA Monitoring Parameters?

Answer 28

Look at HGB, BP, Ferritin, TSat, Serum chemistries, and Reticulocytes: All listed as initial--> maintenance monitoring
-HGB: 2x/week --> 1/2x per month
-BP: 3x/week --> 3x/week (no change)
-Ferritin: Monthly --> Quarterly
-TSat: Monthly --> Quarterly
-Serum Chems: -->2x/month --> 1x/month
-Reticulocytes --> 1x/week --> Quarterly
-

Question 29

Treatment goals of ESA Therapy:

Answer 29

Prevent blood transfusions and Improve QOL (not improving mortality)

Question 30

ESA Pearls

Answer 30

-These do not help mortality!
-Epo-a –> darbepoetin conversion is ~200U to 1 mcg darbepoetin
-IV or SQ Administration
-IV preferred in dialysi
-SQ has longer duration of action and uses lower
dosing
Avoid ESA’s when:
1.) Active malignancy with anticipation of cure
2.) HGB>11g/dl
3.) High risk of CVA

Question 31

When should you use blood transfusions?

Answer 31

When HGB falls below 7g/dl

Question 32

Notes about blood transfusions:

Answer 32

-1 Unit of packed rbc’s can be expected to raise HGB by ~1g/dl
-Each unit contains 200mg of elemental iron
Risks/AEs with blood transfusins:
-Acute Lung injury
-Hypervolemia
-HYPOcalcemia
-Hypersensitivity Rxns
–Immune reactions, problem for transplant candidates (more transfusions menas greater risk of transplant rejection)

Question 33

Vitamin supplementation

Answer 33

Dialysis patients usually get a special IV multivitamin (Nephro-Vit) that has a lot of water soluble vitamins depleted by dialysis- has B12, folic acid)