diagnosis and treatment of CKD related anemia

1. Anemia management in ESRD
Dr forghani . MD

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)