CKD Anemia

Question 1

Patho of CKD Anemia

Answer 1

• PRIMARY CAUSE: decreased production of EPO by kidney (normally supplies 90% of body’s EPO)
• Uremia: shortens RBC lifespan
• Changes in Fe regulation: hepcidin
• Hyperparathyroidism
• Infection or inflammatory conditions
• Blood loss form hemodialysis or blood draws
• Platelet dysfunction: GI bleed
• RBCs destroyed during hemodialysis
• Water soluble vitamins removed by dialysis

Question 2

Presentation of Anemia

Answer 2

• Pallor
• Fatigue
• Tachycardia
• Dyspnea
• Poor exercise tolerance
• Angina
• Anorexia
• Cold extremeties
• Weakness
• Depression
• Insomnia/excessive sleepiness
• LVH (left ventricular hypertrophy)
• Decreased cognitive function, mental alterness, energy level, and sexual function

Question 3

Why treat Anemia?

Answer 3

-Hbg < 10 g/dL has been shown to have clear evidence towards LVH, deterioration in cerebral function, and decreased quality of life

Question 4

CV Consequences of Anemia

Answer 4

Reduced Hgb ==> Tissue Hypoxia ==> Increased cardiac workload and neurohormonal activation ==> LVH/IHD (also encourage the development of one another) ==> CHF, MI, arrhythmias

Question 5

Hemoglobin Reference Ranges

Answer 5

• Men: 14.5 - 18 g/dL

- Women: 12 - 16 g/dL

Question 6

What to always assess/fix first

Answer 6

IRON

Question 7

Iron to Treat Anemia

Answer 7

• Anemic + Not on iron/ESA, recommend trial IV iron if: increase in ESA without starting ESA desired and TSAT =< 30% and ferritin is =< 500 ng/mL
• Goal: keep Hgb > 10 g/dL to avoid ESA therapy

-ESA patients not on iron, recommend iron trial if: increase in Hgb or decrease in ESA dose desired and TSAT =< 30% and ferritin is =< 500 ng/mL

Question 8

Iron to Treat Anemia

Answer 8

Minimum TSAT/[Ferritin]:
CKD-ND, CKD-PD
-TSAT > 20%
-Serum ferritin > 100 ng/mL

CKD-HD

• TSAT > 30%
• Serum ferritin > 200 ng/mL

Question 9

Oral Iron Preps

Answer 9

-Recommended dose: 200 mg elemental iron/day

Question 10

Iron Formulation + Amount of Elemental Iron

Answer 10

• Ferrous gluconate 315 mg = 36 mg elemental iron
• Ferrous sulfate 325 mg = 65 mg elemenntal iron
• Ferrous fumarate 300 mg = 99 mg elemental iron
• All other formulations are 100% elemental iron

Question 11

Oral Iron AE

Answer 11

• GI symptoms: dyspepsia, N/V, abdominal cramping
• Constipation/diarrhea
• Dark Stools

Question 12

Oral Iron Drug Interactions

Answer 12

• Food can decrease absorption
• Antacids can decrease absorption
• Drugs that increase pH (PPIs and H2RAs) can decrease Fe absorption

Question 13

Oral Iron + Food

Answer 13

• Recommended to take on an empty stomach

- If not tolerated, can take with food

Question 14

Oral Iron decreases absorption of….

Answer 14

• Levothyroxine
• Antibiotics: quinolones, tetracyclines
• Some HIV medications

Question 15

IV Iron Preps

Answer 15

• Iron dextran (INFeD)
• Iron sucrose (Venofer)
• Ferric carboxymaltose (Injectafer)
• Ferric pyrophosphate citrate (Triferic)
• Ferumoxytol (Feraheme)
• Sodium ferric gluconate (Ferrlecit)

Better for dialysis patients

Question 16

IV Iron + Anaphylatic Reactions

Answer 16

• Reported with ALL formulations of IV Fe
• Highest rates seen with iron dextran (test dose of 25 mg first)
• Sodium ferric gluconate, iron sucrose, ferumoxytol have better safety records
• Observe during and immediately following administration for at least 30 minutes and until stable (60 minutes for dextran)
• Crash cart and personnel available to provide treatment)

Question 17

Iron Overload

Answer 17

• Excess iron can deposit in the tissues
• Can cause dysfunction of key organs like heart, pancreas, and liver
• Evaluate holding iron when ferritin > 500 ng/mL

Question 18

Is it okay to give IV iron when they patient has an active systemic infection?

Answer 18

No

Question 19

Monitoring for Iron Therapy

Answer 19

• Assess iron before starting ESA
• Test more frequently with ESA introduction/dose changes, with blood loss, and when monitoring response to course of IV Fe
• Test every 3 months for patients on stable ESA dose
• Monitor CBC for Hgb levels

Question 20

Targets of Iron Treatment

Answer 20

• Ferritin

- TSAT

Question 21

Erythropoietic Stimulating Agents

Answer 21

• ESA
• Same biological effects as endogenous EPO
• Stimulates erythroid progenitor cell proliferation and differentiation
• Increases Hgb synthesis
• Induce release of reticulocytes from bone marrow into blood stream

Question 22

ESA Products

Answer 22

• Epoetin Alfa
• Darbepoetin Alfa
• Methoxy Polyethylene Glycol-Epoetin Beta

Question 23

Epoetin Alfa

Question 24

Epoetin Alfa

Answer 24

• Epogen (Amgen), Procrit (Janssen), Retacrit (Pfizer, biosimilar)
• 30 kDA - amino acid sequence similar to natural EPO
• 1/2 Lives: IV = 4-13 hours, SC = 19-25.3 hours

Question 25

Darbpoetin Alfa

Answer 25

- Aranesp (Amgen) - 2 additional carbohydrate chains - larger molecular weight (37 kDa) - 1/2 Lives (longer than Epoetin): IV = 25.3 hours, SC = 28.8 hours

Question 26

Methoxy Polyethylene Glycol-Epoetin Beta

Answer 26

- Mircera (Roche) - 60 kDa - Longest half lives: IV = 134 hours, SC = 139 hours

Question 27

When to Start ESA?

Answer 27

- Use with great caution, if at all, in CKD patients with: active malignancy, history of malignancy, history of stroke - If on dialysis, start ESA when Hgb is 9-10 g/dL - If not on dialysis and Hgb < 10 g/dL, individualized based on many factors

Question 28

Individualized Factors + ESA Initiation

Answer 28

- Rate of Hgb fall - Prior response to Fe therapy - Risk of needing blood transfusion - Risk related to ESA therapy - Presence of anemia-related symptoms

Question 29

ESA Starting Doses

Answer 29

Epoetin Alfa -Dialysis/Non-dialysis: 50-100 U/kg IV/SC 3x/week Darbepoietin Alfa - Dialysis: 0.45 ug/kg IV/SC every week or 0.75 ug/kg q2w - Non-Dialysis: 0.45 ug/kg SC q4w Epoetin Beta -Dialysis and Non-dialysis: 0.6 ug/kg IV/SC q2w

Question 30

Hgb Levels + ESA

Answer 30

- Should not be used to maintain [Hgb] > 11.5 g/dL | - Should not be used intentionally to increase [Hgb] > 13 g/dL

Question 31

Epoetin Alfa Dose Adjustments

Answer 31

- Monitor Hgb at least every week while adjusting/starting therapy until stable, then at least once a month - Do not increase dose more than once a month - If Hgb increases >1 g/dL in 2 weeks, decrease dose by >=25% - If Hgb dose not increase >1 g/dL after 4 weeks, then increase dose by 25% - For patients who don't respond adequately over 12 week period, increases in ESA is unlikely to improve response and may increase their AE risks

Question 32

Causes for ESA Resistance

Answer 32

- Iron deficiency - Vitamin deficiencies: folic acid, B12 - Drug-induced anemia - Patient compliance with ESA, iron, dialysis - PRCA - Also infection, malnutrition, malignancy, blood disease, intoxications, blood loss, inadequate dialysis

Question 33

Pure Red Cell Aplasia

Answer 33

- PRCA - Develop neutralizing antibodies to EPO - Presentation: sudden loss of response to ESA therapy (Rapid drop in Hgb), low reticulocyte count - Management: D/C ESA agent and do NOT switch to a different agent - Can also use corticosteroids + cyclosporine/cyclophosphamide, blood transfusions for anemia

Question 34

ESA AE

Answer 34

- Common: HTN - Serious: increased mortality, MI, stroke, and thromboembolism - Seizures - PRCA