2. Renal anemia
• Anaemia is a frequent complication in patients with chronic kidney
disease (CKD) and is a risk factor for morbidity
• anemia is an independent predictor of CKD progression
• Decreased haemoglobin level is important predictors of LVH
• Blood transfusions potentially trigger humoral allosensitization
of patients with ESRD awaiting a kidney transplant, thereby
reducing the chances of the patient receiving a transplant.
Anemia in CKD associated with
↓ QOL
↓ energy and exercise capacity
↓ neurocognitive function
↑ mortality
↑ LVH rate
3. Diagnosis
• The National Kidney Foundation (NKF) Kidney Disease Outcome Quality
Initiative (K/DOQI) guidelines recommend that patients with CKD undergo an
assessment for the cause of anemia when the Hb is 12.5 g/dL in adult males
and 11.0 g/dL in adult females.
• The routine evaluation of patients with CKD includes various measurements,
such as tests for:
red blood cell (RBC) indices,
iron levels, transferrin saturation
(TSAT)
serum ferritin
occult blood in the stool
4. Etiology
Due to insufficient production of the
glycoprotein hormone erythropoietin
primarily due to a relative lack of EPO
shortened red blood cell survival
uraemic and cytokine inhibition of erythropoiesis (especially infections and
inflammatory conditions)
iron deficiency
hypothyroidism
active blood loss (including HD circuits, GI bleeding);
haemolysis
haemoglobinopathies
aluminium overload
hyperparathyroid osteitis fibrosa
folic acid or vitamin B12 deficiency
5. Consequences of anemia
• Symptoms
• Physical examination
Fatigue, reduced exercise tolerance
Dyspnea/Shortness of breath
Syncope/faintness
Palpitations , Angina if pre-existing CAD
Cognitive impairment , memory concentration ,
decreased cognition and mental acuity
Loss of libido
Altered menstrual cycles
Erectile dysfunction
Pallor
Hyperdynamic circulation
Later, heart failure may occur.
LVH
6. Etiology
Patients with stage 5 CKD undergoing haemodialysis experience a
concomitant loss of iron that amounts to 1.5–3 g per year and needs to
be replaced using intravenous iron therapy.
Red blood cell losses associated with hemodialysis equate to iron losses
of 6–7 mg daily in addition to physiological iron losses of 1–2 mg
daily
Increased loss
Stress ulceration from chronic disease may result in GIT loss
Dialysis
• HD pts lose ~ 2.5 L/yr
Accelerated Breakdown
Impaired cell survival (90 days Vs 120 days)
Patients of hemodialysis have RBC destruction
7. Investigation of anemia
The National Kidney Foundation (NKF) Kidney Disease Outcome Quality
Initiative (K/DOQI) guidelines recommend that patients with CKD undergo
an assessment for the cause of anemia when the Hb is 12.5 g/dL in adult
males and 11.0 g/dL in adult females
8. The 2012 Kidney Disease: Improving Global Outcomes (KDIGO)
guidelines suggested using ESAs in patients with the following criteria:
hemoglobin level of 11- 12 g/dL,
iron status has been evaluated and iron deficiency corrected
other treatable causes of anemia should be excluded or treated
and patient should not have a history of active malignancy ( Hb 9-10)
Medications ( ESA):
Epoetin alfa 8h half life
Darbepoetin alfa 24 h half life
Indications for ESA therapy and target hemoglobin
After CKD related anemia diagnosis
9. Benefits of anemia treatment with ESA
With anemia correction:
•Outcomes improvement
•Reduction in transfusion-related complications
•Improved quality of life and overall sense of well-being
Route of ESA administration
• Subcutaneous versus intravenous ESAs
High efficacy, dose reduction 25%, long half life but pain full in SC route
Side effects of ESA therapy • Worsening of hypertension
• Seizures
• Graft clotting
• Stroke
• Effect on Kt/V
10. Dosing
• Initial dose 2000-3000 U
three times /w
• Evaluation of response
after 1-2 w
• Individualized anemia
management with ESA
adjustment
• Evaluation After
achievement of Hb
target Q 2-4 w
11. Causes of ESA not working
• Iron deficiency ** most common **
• B12 & Folate deficiency
• Inflammation
• ACE inhibitors
• Hyperparathyroidism – bone marrow fibrosis
• Aluminium toxicity
• Inadequate dialysis
• Malignancies, including multiple myeloma
• As approximately 15% of patients with ESRD are resistant to ESAs
• Defined as failure to anemia correction despite:
> 450U/kg/w IV or 300 U/kg/w SC Epoetin
12. Iron deficiency
Most common cause of ESA resistance
Diagnosis based KDIGO guideline
• Blood loss (GI loss, circuit and dialyzer, sampling)
• Functional iron deficiency (normal or high ferritin low TSAT)
• Inflammation (reticuloendothelial blockade)
• Poor absorption of dietary iron due to increased hepcidin
• Serum ferritin (<200 mcg/l)
• Transferrin saturation (<20%)
• Reticulocyte hemoglobin content (CHr) < 29-32 pg/cell
13. Iron treatment
• General principles
• Oral iron
• Intravenous iron
iron sucrose 100 mg/ 10 dose then 25-100 mg /w
Not recommended
Risk and complication
Intravenous iron safety: Anaphylaxis
Intravenous iron safety: Infection
Intravenous iron safety: Oxidation
the European Renal Best Practice (ERBP)
position statement suggests that limits of a
TSAT of 50% and a serum ferritin level
of 500 ng/ml should not be exceeded in
patients on dialysis.
14. Other causes of ESA resistance
• Inflammation and infection
• Hyperparathyroidism (PTH inhibit erythropoiesis)
• Vitamin D deficiency (Vit D suppress hepsidin)
• Relative vitamin B12 deficiency (PPI, High flux dialyzer)
• Angiotensin-converting enzyme (ACE) inhibitors (Inhibit EPO effect)
• Pure red cell aplasia (Anti EPO antibody production)
Other treatments
• Red blood cell transfusions ( if needed)
• Carnitine (Increase ESA effect) KDIGO not recommended
• Ascorbic acid (iv infusion can increase ESA effect)