Anemia in CKD

Tee Heng Seong

Outline
• Epidemiology
• Pathophysiology
• Symptoms
• Diagnosis
• Treatment
• References
Epidemiology
• The landmark study by Obrador et al showed that among pre-dialysis
patients, 68% of those with advanced CKD who required renal
replacement therapy had a hematocrit of less than 30 mg/dL; of
those, 51% had a hematocrit less than 28 mg/dL
• A study conducted by Salman et al showed that the prevalence of
anemia was 75.8% in 615 adult pre-dialysis patients receiving
treatment at the HUSM from January 2009 to December 2013.
Mechanism
Typically normocytic normochromic; multifactorial:
• Mainly is due to EPO deficiency (kidney is main source of EPO)
• Shortened RBC lifespans in uremic patients
1. Negative iron balance from
Increased iron losses (1-3g/year) from chronic bleeding (platelet
dysfunction, frequent blood taking, blood trapping in the dialysis
apparatus)
2. Reduced dietary iron intake
3. Impaired iron absorption from gut and release (hepcidin excess)
Signs and symptoms of anemia in
CKD
• Maybe asymptomatic
• Lethargy, near syncope/syncope
• Reduced exercise tolerance
• Orthostatic symptoms
• Chest discomfort, palpitations
• Cold intolerance etc
Diagnosis
• In adults and children >15 years old with CKD:
- Hb <13 g/dL in males
- Hb <12 g/dL in females
• Investigations of anemia
- FBC
- Serum ferritin level
- Iron, TIBC, TSAT
- Serum vitamin B12 and folate levels
Frequency of testing of anemia
CKD patients without anemia CKD patients with anemia

Stage 3 Annually 3 monthly

Stage 4 and 5 (ND) 6 monthly 3 monthly

Stage 4 and 5 (HD) 3 monthly Monthly

Stage 4 and 5 (PD) 3 monthly 3 monthly

Management
• Supplements (oral or parenteral iron, folate, vitamin B complex)
• ESA
• Blood transfusion

** For any individual patient the optimal balance of Hb level, ESA dose,
and iron dose at which clinical benefit is maximized and potential risk is
minimized is not known
TSAT and ferritin levels
• A very low serum ferritin (<30 ng/ml [<30 μg/l]) is indicative of iron
deficiency.
• Except in this circumstance, the TSAT and serum ferritin level have
only limited sensitivity and specificity in patients with CKD for
prediction of bone marrow iron stores and response to iron
supplementation
• Few evidence to support a recommendation for specific TSAT and
ferritin levels at which iron therapy should be initiated or as ‘targets'
for iron therapy
• KDOQI 2006
- supplemental iron should be given to maintain
 ferritin levels >200 ng/ml (>200 μg/l) in CKD 5HD patients
 ferritin levels >100 ng/ml (>100 μg/l) in CKD ND and CKD 5PD
 TSAT >20% in all CKD patients
- largely opinion based

• KDIGO 2012 – for anemic CKD patients without supplemental iron

 suggest iron in patients with TSAT <30% and serum ferritin <500 
ng/ml (<500 μg/l) if an increase in Hb level is desired
 do not recommend routine use in patients with TSAT >30% or
serum ferritin >500 ng/ml (>500 μg/l)
• Limited evidence in patients with CKD about defining any specific
upper limits for iron status targets in guiding iron treatment
- Previous guidelines citing serum ferritin level >500-800 ng/mL (500-
800 ug/L)

• Concerns about high ferritin levels

- Have been associated with higher death rates (?acute phase
reactants)
- Hepatic deposition of iron increases (might be of particular concern
in patients with hepatitis C virus (HCV) infection)
Oral iron supplements
• Oral iron is prescribed to give elemental Fe of 100-200 mg/day

• If the goals of iron supplementation are not met with a 1–3 month
course of oral iron, consider IV iron supplementation

• Side effects of oral iron: GI symptoms (constipation, abdominal pain,

nausea and vomiting, dark stools), dental
- Toxicity: hepatocellular necrosis, bowel perforation, severe
metabolic acidosis with shock
IV Iron Preparations
Two commonly used approaches in CKD 5HD patients:
• Periodic iron repletion,
• Maintenance treatment
• No data support one way over the other
• Any form of IV iron may be associated with potentially severe acute
reactions eg hypotension, dyspnea, anaphylaxis (more common with
dextran group iron)

• Avoid administering IV iron to patients with active systemic infections

 Iron is essential for the growth and proliferation of most pathogens
- Suggestive theoretical and experimental evidence but no clinical
evidence
Oral iron vs IV iron
KDIGO 2012
• CKD ND: the route of iron administration can be either IV or oral
 available evidence supports advantage of IV compared with oral
iron but the mean Hb difference is only 0.31 g/dl

• CKD5 HD: IV iron is preferred

 IV of iron in these patients derived from RCTs and other studies
comparing IV iron with oral iron and placebo, with and without
concomitant ESA treatment led to a greater increase in Hb
concentration, a lower ESA dose, or both.
ESA agents
 Good Bad
• Reduce need for blood • Increased incidence of stroke
transfusion • Hypertension
• Improve quality of life • Venous thromboembolism
• CV events
KDIGO 2012
• For adult CKD ND patients with Hb concentration 10.0 g/dl, ESA
therapy not be initiated
• For adult CKD ND patients with Hb concentration <10.0 g/dl, decide
whether to initiate ESA therapy be individualized
• For adult CKD 5D patients, suggest that ESA therapy be used to avoid
having the Hb concentration fall below 9.0 g/dl (90 g/l) by starting ESA
therapy when the hemoglobin is between 9.0–10.0 g/dl
• Suggest that ESAs not be used to maintain Hb concentration above
11.5 g/dl (115 g/l)
Dosing of ESA
• Objective: an increase in Hb concentrations of 1.0 to 2.0 g/dl (10 to 20
g/l) per month

• Epoetin-alfa or epoetin-beta dosing: 20 to 50 IU/kg body weight

3X/week

• CERA dosing: 0.6 mg/kg body weight once/2 weeks OR 1.2 mg/kg
body weight once/4 weeks
Response: Hb increase not
adequate…
• Epoetin-alfa or epoetin-beta dosage may subsequently be increased
every 4 weeks by a weekly dose of 3 X 20 IU/kg
Response: Hb increasing….

Hb approaching 11.5

Periodic (eg weekly)

Reduce dose by 25%
monitoring

If still increase, can

withhold, wait for Hb If Hb increase >1g/dL
to reduce then restart in any 2 week period,
at 25% lower than to reduce dose by 25%
previous dose
Frequency of monitoring
Group of patients Frequency of monitoring

CKD ND and 5D Initiation phase: monthly

CKD ND Maintenance phase: 3 monthly

CKD 5D Maintenance phase: monthly