This document discusses chronic kidney disease (CKD) and the common problem of anemia it causes. It provides details on:
1) The causes of anemia in CKD including reduced kidney production of erythropoietin and other factors.
2) The symptoms and signs of anemia such as shortness of breath, weakness, and pallor.
3) Current treatment options for anemia in CKD patients which focus on iron supplementation and use of erythropoiesis-stimulating agents (ESAs) to manage hemoglobin levels.
4) Issues with current treatments including hemoglobin fluctuations and the need for more convenient dosing options to improve an
This document discusses chronic kidney disease (CKD) and the common problem of anemia it causes. It provides details on:
1) The causes of anemia in CKD including reduced kidney production of erythropoietin and other factors.
2) The symptoms and signs of anemia such as shortness of breath, weakness, and pallor.
3) Current treatment options for anemia in CKD patients which focus on iron supplementation and use of erythropoiesis-stimulating agents (ESAs) to manage hemoglobin levels.
4) Issues with current treatments including hemoglobin fluctuations and the need for more convenient dosing options to improve an
This document discusses chronic kidney disease (CKD) and the common problem of anemia it causes. It provides details on:
1) The causes of anemia in CKD including reduced kidney production of erythropoietin and other factors.
2) The symptoms and signs of anemia such as shortness of breath, weakness, and pallor.
3) Current treatment options for anemia in CKD patients which focus on iron supplementation and use of erythropoiesis-stimulating agents (ESAs) to manage hemoglobin levels.
4) Issues with current treatments including hemoglobin fluctuations and the need for more convenient dosing options to improve an
This document discusses chronic kidney disease (CKD) and the common problem of anemia it causes. It provides details on:
1) The causes of anemia in CKD including reduced kidney production of erythropoietin and other factors.
2) The symptoms and signs of anemia such as shortness of breath, weakness, and pallor.
3) Current treatment options for anemia in CKD patients which focus on iron supplementation and use of erythropoiesis-stimulating agents (ESAs) to manage hemoglobin levels.
4) Issues with current treatments including hemoglobin fluctuations and the need for more convenient dosing options to improve an
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CHRONIC KIDNEY DISEASE
AND ANEMIA Anaemia Overview
Anemia in CKD is common.
Patient need continuous observation and
appropriate treatment.
Early Detection and Prevention should be the
ultimate goals. Anaemia
• Anaemia is defined as a reduction in the
haemoglobin concentration of the blood
• This results in a decreased oxygen
carrying capacity Anaemia in CKD
• Causes of Anaemia in CKD
– Reduced production of erythropoietin – Blunted response to endogenous erythropoietin – Uraemic toxins – Reduced RBC life span – Deficiency of iron, folate or other nutritional factors – Infection / Inflammation – Blood loss – Secondary hyperparathyroidism Symptoms of anaemia
• Shortness of breath on exercise
• Weakness and lethargy • Palpitations and headaches • Cardiac failure, angina, intermittent claudication and confusion • Visual disturbances due to retinal haemorrhages Signs of anaemia
• Pallor • Hyperdynamic circulation, tachycardia, cardiomegaly • Congestive cardiac failure • Retinal haemorrhages The Link Between CKD and Anaemia
Erythropoietin Circulating stimulates the Red Blood Cells bone marrow
Kidney
Haemoglobin Produces the hormone carries oxygen erythropoietin The Link Between CKD and Anaemia
Less stimulation of Fewer circulating erythroid Red Blood Cells marrow (bone)
Chronic Kidney Disease Less erythropoietin Anaemia produced Why Anaemia is a Problem • As there is less haemoglobin, there is less oxygen in the blood and the body has less energy and cannot function as well
• The heart works harder to deliver oxygen to the body,
the heart enlarges and progressive damage can lead to heart failure
• Cardiovascular disease is the number-one cause of
death in patients with CKD
• Anaemia results in other debilitating serious
complications
• Anaemia may become worse if it is not treated
But what is the scale of the problem? In Summary - Why We Should Care
• Chronic Kidney Disease (CKD) is a major
problem – Affecting 1 in 10 of the population – Globally CKD is increasing
• CKD leads to anaemia which is common and
debilitating
• Anaemia increases the risk of mortality and
hospitalization in CKD patients Anaemia Treatment in Patients with CKD: Management and Unmet Needs Management of Renal Anaemia
• The objective is to correct and maintain the level of
haemoglobin (the oxygen-transporting protein) in the blood
• Before the development of drugs that stimulated red blood
cell production (ESAs) blood transfusions were the only treatment option for individuals with renal anaemia
ESAs Erythropoiesis Stimulating Agents
Pre-1980s Since 1989
K/DOQI: Evaluation and Management of Anemia
For Adults with ≥ Stage 3 CKD:
Assess Hemoglobin level If anemia (HgB ≤ 12) RBC indices/CBC Reticulocyte count Iron studies Test for occult GI bleeding as indicated Medical evaluation of comorbid conditions Erythropoetin levels are usually NOT indicated. Anemia in CKD: Treatment
• Fe Deficiency – Fe Def: Ferritin <100 ng/ml and FeSat <20%
– Treat with FeSO4
• Goal Ferritin 100-500 • Goal FeSat 20-50 • Start oral. May require parenteral replacement. Anemia in CKD: Treatment
• Erythropoietin Stimulating Agents (ESA)
– Utilize if anemia persists with normal iron stores. Anemia Therapy
• Subcutaneous administration of erythropoietin once
to thrice weekly (sometimes less).
• Monthly monitoring of Hb, iron stores.
• Monthly adjustments in EPO dose and frequency to
meet target Hb 11-12 g/dl (HCT 33-36%). What Are Erythropoietin Stimulating Agents (ESAs)?
• ESAs stimulate the
production of red blood cells by stimulating the precursor cells in the bone marrow
• ESAs have revolutionized the treatment of anaemia associated with CKD Addressing Issues in Anaemia Management
• Anaemia management in patients with chronic kidney
disease: a medical success story in the early 1990s because of ESAs
BUT we need innovation
• A medical need still exists – currently we do not treat
anaemia effectively and consistently in all patients Anaemia Treatment in CKD Patients
stimulate RBC production by erythroid precursors in the bone marrow. Issues in Anaemia Treatment in CKD Patients
Shorter acting ESAs have following limitations:
• Hb cycling – fluctuations in Hb over time which may result in
damage to tissues of target organs
• Frequent dosing – which is burdensome for patients, nurses and
administrators
• Limited availability of extended dosing
Current challenges in the management of CKD related anemia – Hb Cycling
• Approximately half of dialysis patients treated with
current ESAs have Hb levels outside the target range at any given time
• More than 90% of hemodialysis patients experience
Hb cycling
• Causes of Hb cycling – Changes in epoetin dose – Iron supplementation practices – Hospitalization – Extending the dosing interval of ESAs with a short half life Hb-target ranges in the last decades
CSN UK RA UK NICE 11–12 >10 g/dL 10.5–12.5 g/dL g/dL CARI CARI 10–12 g/dL in 11–12 g/dL CVD >11 g/dL CVD 12–14 g/dL no 12–14 g/dL no CARI children <2 yr CVD CVD 11–12 g/dL CVD 12–14 g/dL no CVD Haemoglobin Targets
2004 EBPG >11 g/dL
2006 KDOQI 11-13 g/dL
2008 KDOQI 11-12 g/dL
Locatelli et al. Nephrol Dial Transplant 2004;19(Suppl 2):1-43
NKF-KDOQI. AJKD 2001;37(Suppl 1):S182-238; NKF-KDOQI. AJKD 2006;47(Suppl 3):S11-145 There is a medical need for predictable and stable haemoglobin control What advantages a new EPO should have?
• Stable Hb-courses, reliable increase or decrease, if
needed • Less Logistics, storage, administration, nurse duty • Easy to handle dosages, safe injection • Less painful injection • Longer acting ESA for less injections • No difference between i.v. and s.c. • Equal or even more safe as other ESA`s • Cost-effectiveness Endogenous Epoetin – Mode of Action
Stimulation of Erythropoiesis by endogenous Epoetin Recombinant Epoetin – Mode of Action
Stimulation of Erythropoiesis by recombinant Epoetin MIRCERA – Mode of Action (Different Receptor Kinetics
MIRCERA MIRCERA MIRCERA MIRCERA MIRCERA
Continuous stimulation of the erythropoiesis by MIRCERA
