Transcript Renal Anaemia

Renal Anaemia
Dr Anne Kleinitz
KRSS GP
Why is this important?




Anaemia is common in the Kimberley
Multiple causes, but common in CKD and
ESKD.
Anaemia is linked to left ventricular
dysfunction, heart failure, reduced
exercise tolerance and reduced quality of
life.
Pts who are on erythropoietin eg.
Aranesp, have increased iron
requirements and usually require IV iron.
Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management of renal anaemia

Case studies
Definition of Anaemia
•
Greek term for “no blood”
•
Term used to refer to a shortage of
red blood cells (RBC) or a reduciton
in their haemaglobin (Hb) content.
Hb is a molecule in RBCs that
carries oxygen.
May be due to low red cell mass, or
increased plasma volume (eg.
pregnancy)
•
•
Hb level in anaemia
•
•
•
•
Male <13.5 g/dL
Female <11.5g/dL
In CKD aim for Hb between 11 – 12
g/dL (see CKD protocol)
Level at which we consider EPO in
CKD < 10.0 g/dL
Erythropoeisis




RBCs develop in the bone marrow
as stem cells, then evolve into
erythroblasts.
Erythropoeitin (EPO) is a hormone
secreted (90%) from proximal renal
tubules.
EPO stimulates stem cells in the
bone marrow to  RBC production.
Iron essential in latter phase as Hb
incorporated into reticulocytes and
released into circulation as RBCs

2/3rds of iron in the body is in Hb
Renal Anaemia

Anaemia of renal failure is
normocytic and normochromic

ie. Normal size and normal Hb
concentration

Unless they also have iron deficiency
Classification of Anaemia

Mean cell volume (MCV)

average size of one RBC

Microcytic
MCV < 80

Normocytic 80 - 100

Macrocytic > 100
Microcytic MCV <


Iron deficiency anaemia – most
common
Thalassemia
Microcytic hypochromic RBCs
Normocytic







Acute blood loss
Anaemia of chronic disease
Bone marrow failure
Renal failure
Hyopthyroidism (or  MCV)
Haemolysis (or  MCV)
Pregnancy
Normocytic RBCs
Macrocytic








B12 or folate deficiency
Alcohol excess or liver disease
Reticulocytosis (eg. With
haemolysis)
Cytotoxics
Myelodysplastic syndromes
Marrow infiltration
Anti-folate drugs (eg. Phenytoin)
Hypothyroid
Macrocytic/megaloblastic
RBCs
Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management of renal anaemia

Case studies
Causes of Anaemia
•
•
•
Reduced production of RBC
Accelerated breakdown of RBC
Increased loss of RBC
Causes of Anaemia in renal
failure
•
Reduced Production of RBC
• May be secondary to shortage of RBC
precursors such as Iron, B12 and folate.
• Reduced oral intake
•
•
•
Reduced absorption
•
•
•
on a low phosphate or protein diet this may
effect dietry iron
Uraemic patients may have reduced appetites
Phosphate binders may reduce absorption
Proton pump inhibitors
Inadequate erythropoietin, 90% produced
in kidneys, the hormone that stimulates
erythropoiesis (manufacture of
erythrocytes)
•
•
Accelerated Breakdown
• Impaired cell survival (90 days Vs
120 days)
• Patients of haemodialysis have
RBC destruction.
Increased loss
• Stress ulceration from chronic
disease may result in GIT loss
• Dialysis
•
HD pts lose ~ 2.5 L/yr
Anaemia in CRF
Anaemia in CKD



Significant anaemia noted once
eGFR < 40
Even with eGFR 30 – 40,
consider other causes of
anaemia
Beware of anaemia that is out of
proportion to level or renal
impairment.
Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management

Case studies
Symptoms
•
Fatigue, reduced exercise tolerance
•
Dyspnoea/Shortness of breath
•
Syncope/faintness
•
Palpitations. Angina if pre-existing CAD
•
Cognitive impairment; memory
concentration
•
Loss of libido
•
Altered menstrual cycles
•
Erectile dysfunction
Signs

May be absent

Pallor – eg. Conjunctivae

Hyperdynamic circulation


Tachcardia

flow murmur (ESM, loudest over apex)

cardiomegaly
Later, heart failure may occur.
Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management

Case studies
Investigations

FBC







Hb
WCC
Platelets
MCV
RCC
Htc
B12




Iron

Ferritin

Transferrin

Transferritin
saturation (TSAT)
necessary for rapid
synthesis of DNA
during cell division
Folate

Iron studies
Required for cell
division in bone
marrow to produce
RBC’s

CRP

Inflammatory marker
Reticulocyte count

Erythrocyte precursors that are released from
the bone marrow and circulate in the blood as
they mature into RBC’s

Indicates the level of erythropoietic activity in
the bone marrow

Normal 0.2% – 2%

Most helpful if very low (<0.1%) or greater than
3%

Decreased reticulocytes seen in EPO
deficiency, Iron , vitamin B12 and folate
deficiency.
Target Hb
CARI Guidelines - 2005

Minimum Hb concentration in
dialysis pts is 110 – 120 g/L

In CKD

Males < 13.5 g/dL


(<12 g/dL if > 70 years)
Female < 11.5 g/dL
Objectives

Definition of Anaemia

Causes

Symptoms and Signs

Investigations

Management

Case studies
Management of renal anaemia





Look for other causes of anaemia
 ? malignancy
Correct other RBC precursors
 B12, folate
 Intravenous Iron supplementation
Correct EPO deficiency with erythropoietin
replacement therapy (ERT)
Blood transfusions - very cautiously
Monthly monitoring of Hb and ferritin.
ERT available in WA

Eprex (Epoeitin alpha)





IV only
3 x wk
Most HD pts on this
Neorecormon (Epoeitin beta)
Aranesp (Darbepoeitin)
IV or SC
 extra carbohydrate chain, 3 x longer half
life, hence can be given weekly or
fortnightly (non-dialysing pts).
** Cold chain required for ERT. **

Initiating ERT


Started by nephrologist
For funding pts need to meet S100
criteria



GFR less then 60mls/min
Hb less than 100 g/L
Before commencing therapy



Iron stores *** likely an ongoing
requirement
red cell folate
Vitamin B12
EPO administration

Avoid increases greater than
10g/L month

Generally adjustments 25% of
dose

Aim for Hb110 – 120 g/L
TSAT > 20%
 Ferritin around 600

Logistics of Aranesp
Robyn’s demonstration of use…
Concerns with ERT therapy

Hypertension, especially if Hb 
quickly
Ideally < 180 systolic.
 Discuss with renal GP if unsure
 HPT may be indicative of fluid
overload, so may need 2/24 bags
prior to EPO


Seziures


Up to 3% in first 3/12 of Rx
Pure red cell aplasia (PRCA)
Causes of EPO not working








Iron deficiency ** most common **
B12 & Folate deficiency
Inflammation
ACE inhibitors
Hyperparathyroidism – bone marrow
fibrosis
Aluminium toxicity
Inadequate dialysis
Malignancies, including multiple
myeloma
Iron studies



Ferritin
 Iron storage protein, giving an indirect
measurement of stored iron
 ↓ ferritin always Iron def, but high in
inflammation (inflammatory marker)
Transferrin
 Transports iron from stores to the bone
marrow.
Transferrin saturation
 Gives a measure of the iron available to
bone marow
 Useful to detect functional iron
deficiency
Iron Deficiency – definition
TSAT
Ferritin
Ferritin

< 20%
< 100ug/L (not on EPO)
< 300ug/L ( on EPO)
Like to see ferritin around 600
Iron Supplementation

Oral


IM


Suboptimal,limited absorption,side
effects
Painful,discolouration,muscle
sarcomas,variable absorption
IV


Ideal. Single and maintenance
dosing (500mgs)
Iron polymaltose

Or Iron sucrose if polymaltose not
tolerated
Iron Polymaltose


Very well tolerated
Recent study (Dec 2008) in Australia
showed of 503 infusions on 260 pts


No anaphylaxis
7 patients (2.7%) had some side effect (SE)





2 x urticaria – 2nd infusion. Have since had further
Tx with no SEs
2 x nausea and vomiting – 1st infusion. Rechallenged, again SE’s so changed to Iron
sucrose.
1 x nausea and itching – had previously had
uneventful Tx – given Iron sucrose with no SEs
1 x hypotension – within 1 hour of 1st infusion.
Ceased then recommenced slower with no further
problems.
1 x burning sensation in neck, scalp and groin at
1st infusion, has since had further Tx (at lower
dose as on HD) with no SEs

This recent Australian study,
showed no anaphylactic
reactions and only a small
number with milder reactions
such as n & v, rash and urticaria
which resolved quickly.
Iron Infusion

Iron Infusion



500 mg Iron Polymaltose (Ferrosig)
5 x ampoules $30 ($6 ampoule)
Iron Sucrose PBS listed (S100) $140 5 x
ampoules


If on EPO, iron deficient and documented
adverse reaction to polymaltose
Aranesp


100 mcg 4 x pre-filled syringe (1 x box)
cost $1400.
40 mcg 4 x pre-filled syringes (1 x
box) cost $600

Given the cost of EPO to
correct anaemia, it’s important
to maintain adequate iron
stores to optimise its response.
Causes of iron deficiency




ERT stimulates erythropoiesis
and increases demand for iron
Decreased iron absorption
Blood loss
Functional iron deficiency
Iron deficiency in HD
•
•
•
•
•
Exacerbated by blood loss
HD pts lose 2.5L blood each year
(1 – 3g of iron/yr)
50-100 mg /wk replacement
needed to offset loss
Pre ESRD and PD pts loose
approximately 250 ml/yr
Further exacerbated by poor GI
iron absorption
Iron – CARI Guidelines 2005



Regular Assessment ( 3 monthly) at initiation
of EPO therapy to maintain sufficient iron
stores
Target Serum Ferritin 200 – 500 ug/L
TSAT 30 – 40%

Goal is for IV Fe to maintain target Hb
without risk of iron overload

Delay blood sampling after Iron infusion for 2
weeks as takes time to be absorbed (false
low reading)
Anaemia and blood
transfusions





Please try to avoid!
Hb < 80 g/L and symptomatic
Blood transfusions expose patients to
white blood cells in the transfusion which
have human leucocyte antigens (HLA) on
their surface. The patients then produce
HLA antibodies - “sensitization” - making
it more difficult to find a good donor
match for a future kidney transplant.
If transfusions are necessary then use a
leucocyte filter.
If you’re not sure who is on the list ask
the renal GP
Case Studies
Mr CA





Age 60.
eGFR 55, creat 100
Hb 80
Iron studies; TSAT 12%
Ferritin 100
Mx?
Anaemia in CRF

Iron deficient BUT anaemia
unlikely related to renal failure
(anaemia usually once eGFR < 40)

Ix for other causes
? Malignancy
 GIT bleeding

Similar to last case…




Male in 50s.
Creat 140, eGFR 45
Hb 100. Iron deficient anaemia.
LMO Mx
EPO
 Nil further investigations….
 Pt later diagnosed with Ca bowel

Ms PD






30 female.
On PD. Aranesp 20 mcg SC
weekly
eGFR 5, creat 500
Hb 80 MCV 70
Iron studies; TSAT % 11 Ferritin
100
Mx?


Iron deficient. Microcytic Anaemia.
Rule out other causes then;

Correct Iron with IV Iron infusion (500mg
APP)


NB. Can give 1500 mg but in Kimberley stick
to 500mg and aim to do regular (less change
of adverse reaction with smaller dose)
Re-check bloods. Once iron, B12 and
folate OK, may need to increase EPO.
Mrs PD 2



Same as last patient, except TSAT
30% ferritin 600
PD pt – poor compliance. Admitted
to ED with APO/fluid overload
What part of FBC is also helpful?



Htc – 0.15
Haemodiluted
Repeated once adequate dialysis – Hb
95 Ht 0.4
Moral of that story…..

Don’t just treat a number
Treat the patient!
 She needed full history and
examination
 Important to remember, so as not
to rush into blood transfusions etc.

Mr NY





54 male. On Aranesp
40mcg/fortnightly
eGFR 25, creat 400
Hb 95 MCV 90 Htc 0.4
Iron studies; TSAT 40% Ferittin
600
Mx?




Normochromic anaemia. Not
iron deficient.
Check all other parameters
(folate, B12)
Ensure no other cause for
anaemia identified
May require increased EPO

Discuss with renal GP or Anaemia
coordinator.
Ms AL





40 female. HD patient.
eGFR 3, creat 200 On IV iron
100mg weekly at HD. On IV
EPO (Eprex) 10 000 units 3x wk
Hb 60
Iron studies; Iron TSAT 30%
ferritin 400
Mx?

History



Hb 120 last month
PV bleeding
Examination
HR 120, BP 90/50 (usually 130/80) pale,
feeling unwell.
Management
 Send to hospital! Urgent. Needs Ix for
anaemia and likely transfusion
 Transfuse through a leucocyte filter (to
remove HLA Ag)

Thank You!
[email protected]
References





Jane York. Royal Perth Hospital. Anaemia
Coordinator.
Iron polymaltose use in chronic kidney
disease patients: one units experience.
Anna Lee. Renal Society of Australia J
5(1) 5-8. December 2008
Renal Anaemia learning package.
Catherine Hunter 2004
Managing anaemia in renal failure.
Oxford handbook of Clinical Medicine. 7th
Edition. Oxford Uni Press, 2007.