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Dharmeizar
75.5
80
Hb ≤12g/dl (% patients)
60 53.6
41.6
40
26.7
20
0
1–2 3 4 5
CKD stage
3
all-cause mortality
853 male
Hazard ratio for
patients with
CKD stages 3- 2
5 not yet on
dialysis
1
0
<11.0 >11.0–12.0 >12.0–13.0 >13.0
• Common cause of
hyporesponsiveness to ESA
Hb concentration is:
• Diagnosis of Anemia • <13.0 g/dl in males
• <12.0 g/dl in females
• Initial evaluation:
• Complete blood count (CBC) include Hb concentration,
red cell indices, white blood cell count and differential,
and platelet count
• Absolute reticulocyte count
• Serum ferritin level
• Serum transferrin saturation (TSAT)
• Serum vitamin B12 and folate levels
• For CKD patients with anemia not being treated with an ESA,
measure Hb concentration when clinically indicated and:
• at least every 3 months in patients with CKD 3–5ND and
CKD 5PD
• at least monthly in patients with CKD 5HD
TSAT <20%
Absolute
Low ferritin
level (<100
μg/l)
Iron
deficiency
TSAT <20%
Functional
Normal
Ferritin Level
DIAGNOSIS OF IRON DEFICIENCY
• Ferritin
• Normal kidney function; Absolute iron deficiency serum ferritin
<15 μg/L
• CKD Patients: ferritin level 100 μg/l influenced by inflammation
• Dialysis patient: ferritin level 200 g/L
• Serum ferritin >500 g/L excluding iron deficiency
• TSAT
• The ratio of serum iron to total serum iron-binding capacity
• a measure of circulating iron
• Iron deficiency: TSAT <15% (Normal 16-40%)
• decreases in the presence of acute and chronic inflammation
functional iron deficiency
Diagnostic marker Strengths Limitations
Bone marrow iron Gold standard. Invasive test, semi (but not
content, measured from fully) quantitative.
biopsy
Liver iron content, Gold standard. Invasive test, semi (but not
measured from biopsy fully) quantitative
Serum ferritin Low ferritin levels are highly Moderately high ferritin levels
specific for detection of iron could occur in the setting
deficiency. of non-iron-related
conditions.
Transferrin saturation Higher sensitivity than serum ferritin The denominator (TIBC) can
ratio (iron saturation to detect iron deficiency. be low in malnutrition and/o
Marker of ratio inflammation.
Iron Stores Serum iron Direct measurement of circulating Diurnal fluctuation; can be
iron. low in inflammation.
in CKD Reticulocyte Measures immediate Limited data, reference
haemoglobin content incorporation of iron into levels debatable.
reticulocytes.
Percentage of Similar to reticulocyte Cumbersome specimen
hypochromic red cells haemoglobin content shipment interferes with the
results.
Soluble transferrin Correlates with the number of Mixed applicability data,
receptor transferrin receptors on unknown cut-off levels.
Kovesdy CP. Journal
erythroblasts
of Renal Care
2009;35(S2):14-24 Erythrocyte zinc May be less confounded by Affected by non-iron-related
protoporphyrin inflammation. factors such as lead level.
Hepcidin May detect the presence of Currently there are no
functional iron deficiency due to reliable assays for its
inflammation. measurement.
TREATMENT GOAL OF ANEMIA IN
CKD
• Avoidance of blood transfusions and associated risks such as:
sensitisation against future transplantation
iron overload
blood-borne disease
transfusion reactions
• Reduced hospitalization
• Recommendation:
• serum ferritin levels 100 g/L for patients with CKD
• serum ferritin levels 200 g/L for dialysis patient
• Evaluate Serum ferritin every 3 mo in patients who
are receiving ESA treatment and intravenous iron
supplementation to evaluate iron deficiency or
too much iron supplementation is given
• Upper limit of serum ferritin is >500 µg/L to avoid
potential complications that are associated with
iron therapy
Cardiovascular outcomes
To Do OR Not To Do
IRON REPLACEMENT
Theraputic
Safety
efficacy
Short term
Administration
adverse
oral vs IV
reactions
IV iron
Iron overload
products
• Food interactions
• Tea
• Hepcidin
• Upregulation limits effective absorption of the
small bioavailable iron
All patients received EPO at a dose of 100-150 IU/Kg/week during the study.
If Hb concentration reached 11 g/dL, the EPO dose was decreased by 25%.
Oral iron
p<0.05 Venofer®
p<0.05 p<0.05
600 50 14 7000
6140
496 12.0
500 39.6 12 6000
40 10.0
400 5000 4500
400 10
28.6
30 4000
8
300
20 6 3000
200
4 2000
100 10
2 1000
0 0 0 0
Serum ferritin (µg/L) TSAT (%) Hb (g/dL) ESA dose (IU/week)
at week 12 at week 12 at week 12 at week 12*
Short-term Long-term
Anaphylactic rx Iron overload
Hypotension Infections
Gastrointestinal Oxidative stress and CV
symptoms risk
• i.v. iron doses greater than 400 mg/mo were associated with
higher CV death rates
FERRITIN/ISAT LEVEL AND
OUTCOMES
BENEFITS RISKS
Lower ESA dose and Unknown longterm
treatment costs effect
Posibble prevention of Acute reactions
CV events associated (intravenous):
with high-dose ESA anaphylactoid,
Improvement of heart adbdominal/chest
failure pain, shortness of
breath nausea,
hypotension, pruritus
and rash
Nephron 2015;131:138-144
MANAGEMENT OF REACTIONS TO IV IRON