CKD Anemia Flashcards
Patho of CKD Anemia
- 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
Presentation of Anemia
- 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
Why treat Anemia?
-Hbg < 10 g/dL has been shown to have clear evidence towards LVH, deterioration in cerebral function, and decreased quality of life
CV Consequences of Anemia
Reduced Hgb ==> Tissue Hypoxia ==> Increased cardiac workload and neurohormonal activation ==> LVH/IHD (also encourage the development of one another) ==> CHF, MI, arrhythmias
Hemoglobin Reference Ranges
- Men: 14.5 - 18 g/dL
- Women: 12 - 16 g/dL
What to always assess/fix first
IRON
Iron to Treat Anemia
- 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
Iron to Treat Anemia
Minimum TSAT/[Ferritin]:
CKD-ND, CKD-PD
-TSAT > 20%
-Serum ferritin > 100 ng/mL
CKD-HD
- TSAT > 30%
- Serum ferritin > 200 ng/mL
Oral Iron Preps
-Recommended dose: 200 mg elemental iron/day
Iron Formulation + Amount of Elemental Iron
- 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
Oral Iron AE
- GI symptoms: dyspepsia, N/V, abdominal cramping
- Constipation/diarrhea
- Dark Stools
Oral Iron Drug Interactions
- Food can decrease absorption
- Antacids can decrease absorption
- Drugs that increase pH (PPIs and H2RAs) can decrease Fe absorption
Oral Iron + Food
- Recommended to take on an empty stomach
- If not tolerated, can take with food
Oral Iron decreases absorption of….
- Levothyroxine
- Antibiotics: quinolones, tetracyclines
- Some HIV medications
IV Iron Preps
- Iron dextran (INFeD)
- Iron sucrose (Venofer)
- Ferric carboxymaltose (Injectafer)
- Ferric pyrophosphate citrate (Triferic)
- Ferumoxytol (Feraheme)
- Sodium ferric gluconate (Ferrlecit)
Better for dialysis patients
IV Iron + Anaphylatic Reactions
- 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)
Iron Overload
- 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
Is it okay to give IV iron when they patient has an active systemic infection?
No
Monitoring for Iron Therapy
- 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
Targets of Iron Treatment
- Ferritin
- TSAT
Erythropoietic Stimulating Agents
- 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
ESA Products
- Epoetin Alfa
- Darbepoetin Alfa
- Methoxy Polyethylene Glycol-Epoetin Beta
Epoetin Alfa
Epoetin Alfa
- 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
Darbpoetin Alfa
- 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
Methoxy Polyethylene Glycol-Epoetin Beta
- Mircera (Roche)
- 60 kDa
- Longest half lives: IV = 134 hours, SC = 139 hours
When to Start ESA?
- 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
Individualized Factors + ESA Initiation
- Rate of Hgb fall
- Prior response to Fe therapy
- Risk of needing blood transfusion
- Risk related to ESA therapy
- Presence of anemia-related symptoms
ESA Starting Doses
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
Hgb Levels + ESA
- Should not be used to maintain [Hgb] > 11.5 g/dL
- Should not be used intentionally to increase [Hgb] > 13 g/dL
Epoetin Alfa Dose Adjustments
- 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
Causes for ESA Resistance
- 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
Pure Red Cell Aplasia
- 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
ESA AE
- Common: HTN
- Serious: increased mortality, MI, stroke, and thromboembolism
- Seizures
- PRCA
