Management Of Anemia In Chronic Kidney

Disease

Presented By:Boushra M. Alsaor

[Pharm D intern]

Al Maaefa college

Definition

Anemia has been defined by the World Health Organization (WHO) as a hemoglobin (Hgb) concentration:

<13.0 g/dL for adult males and postmenopausal women <12.0 g/dL for premenopausal women .

Prevalence

Based upon these criteria, nearly 90 percent of patients with a glomerular filtration rate (GFR) <25 to 30 mL/min have anemia, many with Hgb levels <10 g/dL.

Several factors are responsible for anemia in CKD

Decreased erythropoietin production (most important). Shorter life span of RBCs. Blood loss during dialysis. Iron deficiency. Anemia of chronic disease. Renal osteodystrophy.

Treatment of anemia in CKD can

Decrease morbidity/mortality. Reduce left ventricular hypertrophy. Increase exercise tolerance. Increase quality of life.

Anemia work-up

Initiate evaluation when CrCl is less than 60 mL/minute or hemoglobin is less than 11 g/dL. Hemoglobin/hematocrit. Mean corpuscular volume. Reticulocyte count. Iron studies:

Transferrin saturation (total iron/total iron-binding capacity)—Assesses available iron.

Ferritin—Measures stored iron.

Stool guaiac.

Treatment options

Iron. Erythropoietin stimulating agent(ESA). Blood transfusion. Folic acid and vitamin B12.

Erythropoiesis-stimulating agents (ESAs)

Epoetin-α Same molecular structure as human erythropoietin (recombinant DNA

technology). Binds to and activates erythropoietin receptor. Administered either SC or IV.

Darbepoetin-α Molecular structure of human erythropoietin has been modified from 3

N-linked carbohydrate chains to 5 N-linked carbohydrate chains; increased duration of activity. The advantage is less-frequent dosing.

Binds to and activates erythropoietin receptor.

When to start ESA and Hemoglobin goal

Risk vs benefit. Address all correctable causes of anemia (including iron deficiency and

inflammatory states) prior to initiation of ESA therapy. In non dialysis Patients:

Consider starting ESA treatment only when the Hgb level is <10 g/dL and reduce or stop the ESA dose if the Hgb level exceeds 10 g/dL.

For patients on dialysis: Initiate ESA treatment when the Hgb level is <10 g/dL and reduce or interrupt the ESA

dose if the Hgb level approaches or exceeds 11 g/dL

Try to maintain goal Hgb levels between( 10.0 and 11.5 g/dL). Avoid hemoglobin concentration greater than 13 g/dL.

Dosing

Epoetin-alfa or epoetin-beta dosing usually starts at: 20 to 50 IU/kg body weight three times a week.

Darbepoetin-alfa dosing usually starts at: 0.45 mg/kg body weight once weekly by SC or IV administration. 0.75 mg/kg body weight once every 2 weeks by SC administration.

In patients with a history of CVD, thrombo-embolism or seizures, or in those with high blood pressure, the initial doses should be in the lower range.

The objective of initial ESA therapy is a rate of increase in Hb Concentrations of 1.0 to 2.0 g/dl (10 to 20 g/l) per month.

The rise in Hb of greater than 2.0 g/dl (20 g/l) over a 4-week period should be avoided.

Rapid rising of Hgh can induce hypertension and seizures.

Hemoglobin raising with ESA:

Dosing adjustment

Epoetin-alfa or epoetin-beta dosage may subsequently be increased every 4 weeks by a weekly dose of 320 IU/kg if the increase of Hb is not adequate.

Increases in dose should not be made more frequently than once a month. If the Hb is increasing and approaching 11.5 g/dl (115 g/l), the dose should be reduced by approximately 25%.

If the Hb continues to increase, doses should be temporarily withheld until the Hb begins to decrease, at which point therapy should be reinitiated at a dose approximately 25% below the previous dose.

Adjuvant Therapies

KDOQI guideline recommend not using androgens as an adjuvant to ESA treatment.

Also suggest not using adjuvants to ESA treatment including vitamin C, vitamin D, vitamin E, folic acid, L-carnitine, and pentoxifylline.

ESA Monitoring

1. Hemoglobin concentrations initially every 1–2 weeks and then every 2–4 weeks when stable.

2. Monitor BP because it may rise (treat as necessary).

3. Iron stores:A. Ferritin: HD target is 200–500, and peritoneal dialysis/CKD target is

100–500.

B. Transferrin saturation target is greater than 20% (upper limit of 50% removed from recent guidelines).

Common causes of inadequate response to ESA therapy

1. Iron deficiency is the most common cause of erythropoietin resistance.

2. Infection and inflammation.

3. Other causes: chronic blood loss, renal bone disease, aluminum toxicity, folate or vitamin B12 deficiency, malignancies, malnutrition, hemolysis, and vitamin C deficiency.

Risk of ESA

Higher chance of death was reported and an increased number of blood clots, strokes, heart failure, and heart attacks was reported in patients with chronic kidney failure when ESAs were given to maintain hemoglobin levels of more than 12 grams per deciliter.

Higher chance of death and an increased rate of tumor growth were reported in patients with advanced head and neck cancer receiving radiation therapy and in patients with metastatic breast cancer receiving chemotherapy, when ESAs were given to maintain hemoglobin levels of more than 12 grams per deciliter.

Higher chance of death was reported and no fewer blood transfusions were received when ESAs were given to patients with cancer and anemia not receiving chemotherapy.

Higher chance of blood clots was reported in patients who were scheduled for major surgery and given ESAs.

Iron Therapy

Iron therapy is important to replete iron store. Parenteral iron therapy improves response to ESA and reduce the

dose required to achieve and maintain target indices.

Parenteral VS oral iron therapy

Parenteral therapy is the recommended route for all CKD patients. Most patients with CKD who are receiving erythropoietin therapy

require parenteral iron therapy to meet needs (increased requirements, decreased oral absorption).

Oral therapy is limited by poor absorption and non adherence with therapy due to adverse effects.

Consider oral supplemental iron in ND or PD patient without IV access or as maintenance therapy for ND or PD patients.

Oral route is not recommended in HD patients.

Iron Therapy:

Oral: 200mg elemental iron per day (= 600 mg Ferrous fumarate,1.8g ferrus gluconate or 1gm ferrous sulphate ).

Parenteral:

Adverse effects of iron therapy

Allergic reaction. Hypotension. Dizziness. Dyspnea. Headache. Low back pain. Arthralgia. Syncope. Arthritis.

Some side effects can be reduced by decreasing the dose or rate of infusion.

Sodium ferric gluconate or iron sucrose has better safety profile than iron dextran.

Red blood cell transfusion

ESA therapy is ineffective (e.g., hemoglobinopathies, bone marrow failure, ESA resistance).

The risks of ESA therapy may outweigh its benefits (e.g., previous or current malignancy, previous stroke).

When rapid correction of anemia is required to stabilize the patient’s condition (e.g., acute hemorrhage, unstable coronary artery disease).

When rapid pre-operative Hb correction is required. Transfusion should be directed toward reduction of anemia sign and

symptoms rather than achieving specific target.

Q & A

Thanks For Your Attention…