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Nephrology > Anaemia in CKD > Flashcards

Anaemia in CKD Flashcards

1
Q

What are the causes of anaemia in CKD?

A
  1. Erythropoietin deficiency
  2. RBC trauma from microvascular disease - DM, HTN
  3. Iron and folate deficiency (relative or absolute)
  4. Blood loss from HD, GI bleeding (PUD, angiodysplasia bowel)
  5. Increased oxidative stress
  6. MBD with hyperparathyroidism
  7. Aluminum toxicity
  8. Elevated hepcidin level
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2
Q

How do you evaluate for anaemia in CKD and EPO deficiency?

A
  1. FBC - Hb, MCH, MCV, MCHC
    1A. Mentzer index = MCV / RBC count (< 13 thalassaemia)
  2. Reticulocytes count
  3. Iron panel - serum ferritin (iron stores), tsats
  4. Serum B12/folate levels
  5. FOBT

EPO deficiency is a diagnosis of exclusion

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3
Q

What is functional iron deficiency?
What is the role of IV iron?

A

Functional iron deficiency is a bone marrow iron supply-demand mismatch with normal or elevated iron stores

Treatment with EPO causes bone marrow stimulation to produce RBCs faster than transferrin carrier protein can deliver adequate iron substrate

Investigations: ferritin >200-500; tsats < 20%

IV iron reduces EPO requirements by 20-25%

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4
Q

What are the adverse effects of IV iron?

A
  1. Nausea, vomiting
  2. Hypotension
  3. Allergic or anaphylaxis
  4. Iron accumulation in tissues
  5. Oxidative damage to endothelial cells
  6. Increased risk of infection - patients receiving IV iron had 2.51x CVS events and 2.12x of hospitalisation due to infection
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5
Q

Why are oral iron supplements ineffective in treating iron deficiency in HD patients?

A

Daily iron loss in HD patients 4-7mg
Oral iron absorption 2-4mg only
Functional iron deficiency requires higher levels of storage iron to facilitate release of iron to transferrin

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6
Q

What is the ideal administrative route of ESA?
How do you monitor for target Hb increase?

A

Subcutaneous administration
- Slower absorption
- Longer half life

ESA dose can be reduced 20-30% when switched from IV to SC while achieving the same Hb

Aim Hb increase 0.25 - 0.5 g/dL per week

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7
Q

What is the recommended dose of Recormon?
What is the recommended dose of darbepoietin?
Newer agents (Mircera)

A

Recormon
IV: 50 units/kg three times a week
SC: 30 units/kg three times a week
(or 100 units/kg/week or PD patient or pre-dialysis)

Darbepoietin - longer duration of action (additional side chains)
IV or SC: 0.45mcg/kg weekly or 0.75mcg/kg 2-weekly

Mircera - methoxy-pegylated EPO Continuous Erythropoietin Receptor Activator (CERA)
- Once monthly injection
- Extremely long duration of action (20x longer than Recormon, 6x longer than darbepoietin)
- Half life: 134 hours (5.6 days)
- Starting dose: 0.6 mcg/kg once monthly

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8
Q

Target Hb for patients receiving ESA and its controversy
- CHOIR, CREATE, TREAT studies

A

(FDA non-evidence based recommendation!)

Higher risk of death, adverse CVS event, stroke when target Hb is more than 11.5 g/dL

Retrospective analyses:
1. Risk of adverse outcomes correlated with EPO doses received rather than Hb level achieved
2. Target Hb in principle studies were 13 g/dL (not 11 g/dL)
3. No mortality benefits! Only avoidance of transfusion as main benefit (which impacts sensitisation for transplant)
4. Some quality of life increase for lower baseline Hb compared to higher baseline Hb (7-8 treatment vs 9-11.5 treatment)

Current Aim: lowest ESA dose sufficient to reduce need for RBC transfusion

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9
Q

What are the complications of ESA injections?

A
  1. Pure red cell aplasia - exogenous EPO cross react with endogenous EP resulting in complete loss of RBC precursors
    (almost exclusively from SC injections and due to manufacturer issues causing alterations of EPO protein)
  2. Increase risk of malignancy
  3. Thromboembolism
  4. Increased risk of cardiovascular and stroke
  5. Allergic reaction and anaphylaxis
  6. AVF thrombosis
  7. Decreased dialyser clearance
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10
Q

What are HIF-PH inhibitors?

A

Hypoxia-inducible factor prolyl hydroxylase inhibitors
- Increases HIF and endogenous EPO activity

Examples:
- Daprodustat
- Roxadustat
- Vadadustat
- Molidustat

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11
Q

What should you suspect in patient on haemodialysis with normal to high haemoglobin?

A
  1. OverUF with haemoconcentration
  2. Excessive dose of EPO
  3. ADPKD - cysts functioning to release endogenous erythropoietin
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12
Q

How frequent should you check for anaemia in CKD?

A

CKD G3 - annually
CKD G4-5 - twice a year
CKD G5D - every 3 months

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13
Q

What is the iron panel levels for iron therapy in ESRF?
How frequent to monitor response?
When should you stop iron therapy?

A

Indication: serum ferritin < 500, tsats < 30%

Target:
- PD: serum ferritin > 100, tsats > 20%
- HD: serum ferritin > 200, tsats > 20%

Monitor FBC and iron panel every 3 monthly

Once ferritin > 500, tsats >30%, consider stopping iron as unlikely to respond

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14
Q

What is the recommended dose of elemental iron?

What are the percentage of elemental iron in different oral iron preparations?

A

Recommended dose: 3-4 mg/kg/day, up to 6 mg/kg/day
(Maximum 150-300 mg/day in 2-3 divided dose)

Elemental iron dose and percentage
- Ferrous fumarate 200mg - 66mg (33%)
- Ferrous gluconate 300mg - 36mg (12%)
- Iron polymaltose 100mg - 100mg (100%)
- Ferric citrate 1000mg - 210mg (21%)

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15
Q

What are the causes of failed oral iron therapy?

A
  1. Non-compliance
  2. Poor absorption in uraemia
  3. Decreased dietary absorption due to phosphate binders, functional achlorhydria, PPI
  4. Functional iron deficiency due to ESA therapy, chronic inflammation
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16
Q

How do you monitor for IV iron therapy?
How do you manage adverse reactions of IV iron therapy?

A
  1. Resuscitation equipment
  2. Vitals monitoring
    - Every 15 minutes during infusion
    - Every 30 minutes x2 after infusion
  3. Monitor for tachycardia, hypotension, urticarial rash

Management of adverse reactions
1. Stop ferinject immediately
2. IV fluid infusion if no contraindication
3. Pitiron or corticosteroids
4. If anaphylaxis, start CPR, IV adrenaline, IV hydrocortisone

17
Q

What are the pre-requisites for ESA injections?

A
  1. Adequate nutrition
  2. Haematinics repleted - iron, folate, B12
  3. Correct severe hyperparathyroidism
  4. Avoid aluminum toxicity
  5. Treat any chronic infection or inflammation
18
Q

ESA conversion for Recormon vs Darbepoietin vs Mircera

A

Recormon 2-3x/week -> Darbepoietin once weekly
Recormon once weekly - > Darbepoietin once every 2 weeks

19
Q

What are the contraindications for ESA injections?

A
  1. Uncontrolled hypertension
  2. Known hypersensitivity to EPO or any excipients
  3. Known sensitivity to products derived from mammalian cells
20
Q

What is ESA hyporesponsivenss?

A

Continued need for higher than 300 IU/kg/week doses of Recormon or 1.5mg/kg/week dose of darbepoietin

Two types:
1. Initial hyporesponsiveness: no increase in Hb after 1st month of treatment on appropriate weight based dosing

  1. Acquired hyporesponsiveness: increase in ESA dose up to 50% above stable dose
21
Q

What are the causes of ESA hyporesponsiveness?

A
  1. Blood loss
  2. Haemodialysis
  3. Absolute or functional iron deficiency, B12/folate deficiency
  4. Malnutrition
  5. Underdialysis
  6. Hypothyroidism
  7. Hyperparathyroidism
  8. ACE inhibitor or ARB use
  9. Infection or inflammation
  10. Malignancy
  11. Pure red cell aplasia - anti-EPO antibodies
  12. Bone marrow disorder
22
Q

When do you suspect antibody-mediated pure red cell aplasia?

A

Patient receiving ESA for more than 8 weeks developing:
1A. Sudden rapid decrease in Hb 0.5-1 g/dL per week or
1B. Requires transfusion at rate of 1-2 per week

  1. Normal platelet and white cell count AND
  2. Absolute reticulocte count < 10,000/uL
  3. Excluded parvovirus infection
23
Q

What is the diagnostic investigation for PRCA?
What is the treatment for PRCA?

A

Investigations
1. Exclude Parvovirus
2. Neutralising antibodies against ESA
3. Bone marrow - reduced or absent erythroblast

Treatment
1. Stop all ESA
2. Transfuse in severe symptomatic anaemia
3. Consider immunosuppressive drug

24
Q

Algorithm for Management of Anaemia in CKD

A

Nephrology (9 decks)

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