1 OPTA – Education Initiative OPTA – Optimal Treatment of Renal Anaemia Improving the Efficacy...
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Transcript of 1 OPTA – Education Initiative OPTA – Optimal Treatment of Renal Anaemia Improving the Efficacy...
1
OPTA – Education Initiative
OPTA – Optimal Treatment of Renal Anaemia
Improving the Efficacy and Efficiencyof Renal Anaemia Therapy
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OPTA – Rationale
European Best Practice Guidelines and KDOQI Guidelines provide scientific evidence on optimal treatment of renal anaemia.
European Surveys of Anaemia Management (ESAM I &II,PRESAM, TRESAM) and Dialysis Outcomes and Practice Patterns Study (DOPPS) demonstrate relevant gaps between standards of care of anaemia treatment and daily practice.
OPTA aims to transfer standards of care into daily practice and to optimise efficacy and efficiency of anaemia therapy by focusing on major and minor factors influencing treatment of renal anaemia.
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Content
Diagnosis and start of anaemia treatment
Impact of anaemia in patients with chronic kidney disease
Patient categorisation within stages of chronic kidney disease
Treatment of anaemia in patients with chronic kidney disease
Effects of epoetin therapy at a cellular level
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Diagnosis and Start of Anaemia Treatment
Reasons for delayed start of anaemia treatment
In early stage of CKD anaemia is non-symptomatic, patients adapt to declining Hb-levels
Under estimation that modest decreases in renal function lead to a decrease in Hb levels
Late referral of patients with chronic kidney disease
Late initiation of treatment
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Epidemiology of Anaemia associated withChronic Renal Insufficiency
Hsu et al., J Am Soc Nephrol 2000;13:504–510.
15.5
14.5
13.5
12.5
11.5
10.5
>80 70–80 60–70 50–60 40–50 30–40 20–30 <20
Creatinine Clearance [ml/min]
men
women
Hae
mo
glo
bin
[m
g/d
l]
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Prevalence of Anaemia by Serum Creatinine and Glomerular Filtration Rate
McClellan W et al., Curr Med Res Opin 2004;20(9):1501–1510.
20
40
1380
100
0
Pat
ien
ts [
%]
Serum creatinine [mg/dL]
60
<1.6≥1.6 – <2
≥2 – <2.5≥2.5
≥15 – <30≥60≥30 – <60 <1
5GFR [mL/min/1,73 m2]
Hb ≤ 10 g/dLHb >10 – ≤ 12 g/dLHb ≤ 12 g/dL
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Impact of Anaemia in CKD-Patients on:
Cardiovascular events/LVH
Quality of life (ability to work, exercise capacity)
Hospitalisations
Impact on mortality
Progression of chronic kidney disease
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Impact of Anaemia in CKD-Patients –
Regression of Left Ventricular Hypertrophy
Roger SD et al. J Am Soc Nephrol 2004;15:148–156.
Canadian/Australian multicentre trial – development of LVH
120
115
110
105
100
LV
Mi
[g/m
2]
1-yearinitial 2-year
Hb 12–13 g/dL (n=75)Hb 9–10 g/dL (n=80) P=0.019
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Impact of Anaemia in CKD-Patients –
Impact on Mortality
Kaplan-Meier plots show survival of new end-stage renal disease patients in Network 5 treated with EPO before the initiation of dialysis versus patients who were not treated. Histograms represent risk of mortality associated with EPO use within 3 tertiles of follow-up after starting dialysis: 0–19.3 month, 19.4–31.4 month and ≥ 31.5 month.
Fink JC et al., Am J Kidney Dis 2001;37:348–355.
50
100
75
2.0
1.6
1.2
0.8
0.4
0
Su
rviv
al [
%]
Rela
tive risk o
f mo
rtality
RR=0.82RR=0.82* RR=1.17
Time on dialysis since initiation [month]
*p<0.05
19.3 31.40
15 Rossert et al. J Am Soc Nephrol. 2003;14 (Suppl 2):173-177.
Impact of Anaemia in CKD-Patients –
Progression of Chronic Kidney Disease
Mechanism of progression of kidney disease
Host FactorsAgeSex
EthnicityGenetic susceptibility
HypertensionDiabetes mellitus
Intermediate FactorsHypertension
Anaemia
Renal Failure
Renal DiseaseGlomerulosclerosisInterstitial fibrosis
Environmental FactorsToxic exposures
MedicationsSmoking
Diet
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Epoetin
Increased number ofred blood cells
Increased oxygen delivery
Increased protection against oxidative stress
Decreased tubular damage
Decreased interstitial fibrosis
Anti-apoptotic effectson renal cells (?)
Potential Beneficial Effects of Epoetin Treatment
Rossert et al. J Am Soc Nephrol. 2003;14 ( Suppl 2):173-177.
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Treatment of Anaemia in Patients with Chronic Kidney Disease –
Effect of Anaemia Treatment on Progression of Renal Disease
Effect of EPO on the cumulative renal survival ratein predialysis patients of three groups
Kuriyama S et al., Nephron 1997;77:176–185.
Group I (untreated anaemic, overall)Group II (treated anaemic, overall)Group III (untreated nonanaemic, overall)
80
100
60
40
0
20
Time (months)0 5 10 15 20 25 3530 40
Cu
mu
lati
ve r
en
al s
urv
ival
rat
e [%
]
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Kaplan-Meier plots for doubling of creatinine, renal replacement, or death (A), and replacement or death (B) in the early (–) versus deferred (–) treatment arms
Gouva C et al, Kidney Int 2004;66:753–760.
Pro
po
rtio
n a
live
wit
ho
ut
pro
gre
ssi
on
Pro
po
rtio
n a
live
wit
ho
ut
ren
al
rep
lac
emen
t
A B
Treatment of Anaemia in Patients with Chronic Kidney Disease –
Effect of Anaemia Treatment on Progression of Renal Disease
0.8
0.6
0.4
0
0.2
1.0
Follow-up [months]
0 6 12 18 24 30
0.8
0.6
0.4
0
0.2
1.0
Follow-up [months]
0 6 12 18 24 30
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Patient Categorisation within Stages ofChronic Kidney Disease
CKD patient categories with high risk of anaemia development
Diabetes mellitus
Congestive heart failure
Diseases e.g. vasculitis, lupus erythematosus
Advanced age
Kidney transplantation
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Patient Categorisation within Stages ofChronic Kidney Disease
Patients with diabetes mellitus
Display a higher incidence of anaemia in the earlier stagesof CKD.
Risk of developing anaemia is two to three times higher than CKD patients with comparable kidney function.
Lower Hb-levels are linked with development/worsening of diabetic complications (retinopathy, diabetic nephropathy).
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Patient Categorisation within Stages ofChronic Kidney Disease
Patients with congestive heart failure
Anaemia is correlated with symptoms of congestive heart failure, even in patients with
– preserved renal function
– normal ejection fraction
Patients with systemic diseases
Inflammation/ elevated serum concentrations of C-reactive protein lead to
– decrease in Hb level
– decrease response to erythropoietin
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Patients with advanced age
Elderly patients are more likely to develop anaemia
Patients with kidney transplantation
Post transplant anaemia has a prevalence of 20-40%.
Risk factors in this patient group are:
– decrease in kidney function (GFR)
– immunosuppressive drugs
Patient Categorisation within Stages ofChronic Kidney Disease
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Patient Segments within Stages ofChronic Kidney Disease
Recommendation
Chronic kidney disease patient categories with
– Diabetes mellitus
– Congestive heart failure
– Diseases e.g. vasculitis, lupus erythematosus
– Advanced age
– Kidney transplantation
are at very high risk for anaemia development and should receivea higher level of attention and care
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Treatment of Anaemia in Patients with Chronic Kidney Disease –
Parameters and Conditions that Need to be Monitored
Major Parameters
Kidney function by estimation of glomerular filtration rate
Proteinuria1
Iron status2
Haemoglobin3
C-reactive protein (CRP)4
1 24 h or spot urine protein/creatinine2 Ferritin and transferrin saturation; distinguish absolute or functional iron deficiency in 3 month intervals or according to stages of CKD3 Monitor at every visit, including white cell and platelet count4 Monitor at every visit, preferably high sensitivity CRP
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Minor Parameters
Parathyroid hormone1
BMI and nutrition status (SGA)2
Screen for blood loss or haemolysis3
Serum B12 and folate levels4
Haemoglobinopathies
1 Monitor PTH twice a year (under specific conditions and stages of CKD every three months2 Determine BMI, body mass index and SGA, subjective global assessment in 3 month intervals or according to stages of CKD3 Order a Coombs test for diagnosis of autoimmunolysis if appropriate
Treatment of Anaemia in Patients with Chronic Kidney Disease –
Parameters and Conditions that Need to be Monitored
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Treatment of Anaemia in Patients with Chronic Kidney Disease –
Major Treatment influencing Factors
Intravenous treatment with iron
Inflammation and overt infection1
Underlying disease and co-morbidity2
Chronic allograft nephropathy (CAN) and type of immunosuppression
Age and sex
1 i.e. diabetic ulcers or ADPKD cyst infection2 i.e.vasculitis, chronic inflammatory conditions, congestive heart failure or fluid overload
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Treatment of Anaemia in Patients with Chronic Kidney Disease –
Minor Treatment influencing Factors
BMI and nutrition
Concomitant medication1
Malignancies (recurrent and de novo)
Occult blood loss and haemolytic anaemia2
Parathyroid hormone
Vitamin B12 and folate deficiency
Proteinuria (interstitial nephritis)
Hypothyroidism
Haemoglobinopathy
1 NSAIDS, ACE-inhibitors and angiotensin-II blockers2 Coombs test
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Management of Major Treatment Influencing Factors – Recommendations
Recommendation
If the Hb of the patient is not > 11g/dl, exclude any other factor before treatment that can be related to anaemia.
Iron status should be measured and corrected before anaemia is treated. In practice, the EBPG for haemodialysis patients should be applied for CKD patients.
Patients with absolute iron deficiency should be treated with intravenous iron administration, at least at the start of anaemia treatment.
Epoetin treatment should be started when haemoglobin is below 11 to increase haemoglobin to above 11 g/dl (EBPG) with an option to further increase haemoglobin to 12.5 g/dl (K/DOQI).
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Summary
Anaemia has a significant impact on patients with CKD, and there is substantial room for improvement in its treatment
Anaemia should be diagnosed and treated early to avoid a negative impact on the kidneys and the cardiovascular system
Patients with CKD and diabetes mellitus, chronic heart failure,or kidney transplantation are at very high risk of developing anaemia and should receive a higher level of attention
Efficiency of anaemia treatment can be improved by better management of the major treatment-influencing factors
Erythropoietin stimulates erythroid progenitor cells, has anti-apoptotic effects, and stimulates angiogenesis
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Erythropoietin: an all-purpose tissue-protective agent?
Savino, Ciliberto, Editorial Cell Death and Differentiation 2004;11:S2–S4.
Effects of Epoetin Therapy on Cellular Level
Brain
Heart
IntestineKidney
Peripheral nervesSkin
Spinal cordRetina
EPO