Agape Jul 23 2009 Anemia I

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  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Creatinine clearance used to be the most commonly used estimation of GFR. You measure the amount of creatinine that is cleared from the plasma in a given time period. Cr clearance overestimates GFR because it is secreted into the tubular lumen in addition to being freely filtered. The formula to remember is UV/P Normal is 100-140cc/min and women may have a slightly lower clearance depending on muscle mass.
  • Agape Jul 23 2009 Anemia I

    1. 1. Anemia of CKD Division of Nephrology and Hypertension East Carolina University – Brody School of Medicine
    2. 2. Objectives <ul><li>Understand the diagnosis and evaluation of anemia in CKD </li></ul><ul><li>Be aware of the 4 types of erythropoietic agents </li></ul><ul><ul><li>2 in current use; 2 in development </li></ul></ul><ul><li>Learn how to institute therapy for anemia with iron and erythropoietic agents </li></ul>
    3. 3. Anemia of CKD <ul><li>Normocytic and normochromic </li></ul><ul><li>Reduced production of erythropoietin by the kidney </li></ul><ul><ul><li>Due to reduction of functioning renal mass </li></ul></ul><ul><li>Shortened RBC survival in CKD </li></ul><ul><li>If untreated, the Hct of patients with advanced CKD stablilizes ~25% in the absence of blood loss or hemolysis </li></ul><ul><li>Anemia in CKD is diagnosed by excluding non-renal causes of anemia in a patient with diminished GFR </li></ul>
    4. 4. Anemia is common in pre-dialysis CKD <ul><li>Becomes increasingly common as GFR declines below 60cc/min per 1.73 m2 </li></ul><ul><ul><li>Particularly in diabetics </li></ul></ul><ul><li>15,000 participants in the NHANES study </li></ul><ul><ul><li>Prevalence of anemia: </li></ul></ul><ul><ul><ul><li>1% at an eGFR of 60cc/min per 1.73 m2 </li></ul></ul></ul><ul><ul><ul><li>9% at an eGFR of 30cc/min per 1.73 m2 </li></ul></ul></ul><ul><ul><ul><li>33-67% at an eGFR of 15cc/min per 1.73 m2 </li></ul></ul></ul>Astor, BC et al. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med 2002;162:1401
    5. 5. Benefits of treating anemia in CKD <ul><li>Amelioration of anemia-induced symptoms </li></ul><ul><ul><li>Improved fatigue, weakness, lethargy, anorexia </li></ul></ul><ul><ul><li>Improved quality of life and stamina </li></ul></ul><ul><li>Improved cognition and mental acuity </li></ul><ul><li>Avoidance of repeated blood transfusions and decreased iron burden in patients with iron overload </li></ul><ul><li>Cardiovascular improvement </li></ul><ul><li>Possibly decreased morbidity and mortality </li></ul>
    6. 6. Benefits of treating anemia in CKD <ul><li>Association between anemia in CKD AND increased morbidity and mortality due to: </li></ul><ul><ul><li>Cardiac disease </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><li>Increased risk of hospitalization, hospital length of stay </li></ul></ul>
    7. 7. Evaluation of anemia in CKD <ul><li>When Hgb < 12 g/dL in females and < 13.5 g/dL in males </li></ul><ul><li>Evaluation should include: </li></ul><ul><ul><li>RBC indices </li></ul></ul><ul><ul><li>Absolute reticulocyte count </li></ul></ul><ul><ul><li>Serum iron </li></ul></ul><ul><ul><li>Total iron binding capacity </li></ul></ul><ul><ul><li>% transferrin saturation </li></ul></ul><ul><ul><li>Serum ferritin </li></ul></ul><ul><ul><li>WBC count and differential; platelet count </li></ul></ul><ul><ul><li>Testing for blood in stool </li></ul></ul>
    8. 8. Erythropoietic Stimulating Agents (ESA) <ul><li>Recombinent erythropoietin </li></ul><ul><ul><li>Trade names: Epogen (EPO), Procrit </li></ul></ul><ul><li>Darbepoietin alfa </li></ul><ul><ul><li>Trade name: Aranesp </li></ul></ul><ul><ul><li>3x longer half-life and greater biological activity than recombinant erythropoietin </li></ul></ul>
    9. 9. Erythropoietic Stimulating Agents (ESA) <ul><li>Future therapies: </li></ul><ul><ul><li>EPO mimetics </li></ul></ul><ul><ul><ul><li>Drugs that mimic the action of erythropoietin </li></ul></ul></ul><ul><ul><ul><ul><li>Short peptide sequences (14 AA) that bind to and activate the EPO receptor </li></ul></ul></ul></ul><ul><ul><ul><li>Trade name = Hematide </li></ul></ul></ul><ul><ul><li>CERA </li></ul></ul><ul><ul><ul><li>Continuous Erythropoiesis Receptor Activator </li></ul></ul></ul><ul><ul><ul><li>A pegylated form of recombinant human erythropoietin </li></ul></ul></ul><ul><ul><ul><li>Has the ability to repeatedly activate the erythropoiesis receptor </li></ul></ul></ul>
    10. 10. Iron or EPO? <ul><li>Should work-up anemia before starting EPO </li></ul><ul><li>If iron deficient, should replace iron first </li></ul><ul><ul><li>Maintenance of sufficient iron stores is necessary for an adequate response to ESAs </li></ul></ul><ul><li>K/DOQI suggests maintenance of the following iron values: </li></ul><ul><ul><li>% transferrin saturation > 20% </li></ul></ul><ul><ul><li>Serum ferritin > 100 ng/mL </li></ul></ul>K/DOQI 2006 Anemia guidelines
    11. 11. Dosing of Iron <ul><li>PO iron </li></ul><ul><ul><li>Ferrous sulfate 325mg TID (~200mg/day of elemental iron) </li></ul></ul><ul><ul><li>$$$ but more GI friendly alternatives include: </li></ul></ul><ul><ul><ul><li>Niferex one a day </li></ul></ul></ul><ul><ul><ul><li>Repliva 21/7 one a day </li></ul></ul></ul><ul><li>IV iron </li></ul><ul><ul><li>Ferrlecit </li></ul></ul><ul><ul><li>Venofer </li></ul></ul>
    12. 12. Dosing of recombinant erythropoietin (EPO, Procrit) <ul><li>50 – 100 units/kg/week SQ </li></ul><ul><li>In practice, most patients are dosed by unit dosing (eg, a vial) </li></ul><ul><li>Given 3x/week in dialysis patients, but 1x/week or less in CKD patients </li></ul><ul><li>Considerations when dosing erythropoietin </li></ul><ul><ul><li>Initial hemoglobin level </li></ul></ul><ul><ul><li>Target hemoglobin level </li></ul></ul><ul><ul><li>Clinical setting </li></ul></ul><ul><ul><li>Rate of increase of the hemoglobin level </li></ul></ul>
    13. 13. Monitoring of recombinant erythropoietin (EPO, Procrit) <ul><li>FDA recommends initially checking hemoglobin weekly; in practice hemoglobin levels are monitored every two to four weeks </li></ul><ul><li>Limited evidence suggests that increased mortality in predialysis patients may be due to high erythropoietin doses </li></ul><ul><ul><li>Some suggest keeping dose < 20,000 units per week </li></ul></ul>
    14. 14. Adverse effects of recombinant erythropoietin (EPO, Procrit) <ul><li>Increased risk of adverse cardiovascular effects with increased hemoglobin levels </li></ul><ul><li>Hypertension due to erythropoietin (though less of an issue than in dialysis patients) </li></ul>
    15. 15. Dosing of darbepoietin alfa <ul><li>Starting dose in recombinant erythropoietin-naïve patients with CKD is 0.45 mcg/kg once weekly OR </li></ul><ul><li>60 mcg once every other week </li></ul>
    16. 16. Hemoglobin Targets <ul><li>Controversial </li></ul><ul><li>Probably target hemoglobin of 11 – 12 g/dL is acceptable in predialysis CKD patients </li></ul><ul><li>Higher hemoglobin levels have been associated with adverse cardiovascular outcomes </li></ul><ul><li>If hemoglobin > 12 g/dL on ESA’s, should: </li></ul><ul><ul><li>Decrease the dose OR </li></ul></ul><ul><ul><li>Increase the dosing interval </li></ul></ul>

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