Iron defeciency anemia in hemodialysis patients


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Iron defeciency anemia in hemodialysis patients

  1. 1. ‫بسم ا الرحمن الرحيم‬ ‫1‬
  2. 2. Iron Deficiency in PatientsUndergoing Hemodialysis 2
  3. 3. Agenda…• Rationale• Diagnosis of iron deficiencyAbsolute iron deficiencyBone marrow biopsyFunctional iron deficiencyUpdates• Target• EBM• Trends 3
  4. 4. Rationale…Hemodialysis patients lose an • A higher tolerance foraverage of 1 to 2 g of iron per physical activityyear • An improvement of cognitive and cardiovascularAnemia is a common functionscomplication in patients • A better quality of lifeaffected by chronic kidney • Reduced hospitalizationdisease, especially patients • lower mortalityundergoing hemodialysis.Correction of the anemia yieldsnumerous benefits: 4
  5. 5. Rationale…• In patients undergoing hemodialysis and treated with ESAs, iron-deficient erythropoiesis frequently develops.• The iron deficiency can be absolute (eg, malnutrition, gastrointestinal bleeding, chronic blood retention in the dialysis circuit, and frequent blood collections) or functional (ie, limitation of bone marrow erythropoietic activity by inability to mobilize sufficient iron from body storage sites); in this situation the bodys total iron stores may be normal. 5
  6. 6. Rationale…• The iron deficit limits the effectiveness of the therapy with ESAs, and, to optimize the treatment, patients must receive an intravenous (IV) iron supplement.• Because parenteral iron administration has potential risks that are immediate (eg, toxic effects and anaphylactic reactions) and long-term (eg, decreased polymorphonuclear leukocyte function, increased risk of infections, organ damage)• It is essential to select patients who need iron supplementation. 6
  7. 7. DIAGNOSIS OF IRON DEFICIENCYAbsolute iron defeciency•The percent transferrin saturation (plasma iron divided by totaliron binding capacity x 100, TSAT) falls below 20 percent•The serum ferritin concentration is less than 100 ng/mL amongpredialysis and peritoneal dialysis patients•Or is less than 200 ng/mL among hemodialysis patients. 7
  8. 8. This difference in the serum ferritin level is based uponaccumulating evidence in hemodialysis patients that themaintenance of ferritin levels above 200 ng/mL isassociated with decreased erythropoietin requirements. Rocha LA et al, 2009 8
  9. 9. 9
  10. 10. DIAGNOSIS OF IRON DEFICIENCYBone marrow biopsy Rare in CKD and ESRD •Risk of bleeding and infection Instead any enhancement of erythropoiesis with: •Iron supplementation ++ hemoglobin -- doses of ESA Stancu S et al, 2010 10
  11. 11. DIAGNOSIS OF IRON DEFICIENCYFunctional iron deficiencyCharacterized by : How to differentiate ?• Adequate iron stores •Response to ESAs and inability to sufficiently intravenous iron (50-125mg for mobilize 8-10 doses)• Transferrin saturation ≤20 percent• Elevated ferritin level (typically >100 to 200 ng/mL) 11
  12. 12. DIAGNOSIS OF IRON DEFICIENCYFunctional iron deficiencyDrive study 2007• Administration of ferric gluconate (125 mg for eight treatments) is superior to no iron therapy in anemic dialysis patients receiving adequate epoetin dosages and have a ferritin 500 to 1200 ng/ml and TSAT<or=25%. Coyne DW et al, 2007 12
  13. 13. DIAGNOSIS OF IRON DEFICIENCYUpdates..• To diagnose iron deficiency in patients undergoing hemodialysis, the percentage of hypochromic RBCs (with cellular hemoglobin concentration <280 g/L [HYPO%]) and mean reticulocyte hemoglobin content (CHret) were proposed as alternatives to biochemical tests. Pajola R et al, 2011• Reticulocyte Transferrin R expression reflected the changes in the Hb level and the iron availability at the cellular level, and therefore it might be useful in the assessment of iron status in patients with CRF Soininen K et al, 2010 13
  14. 14. DIAGNOSIS OF IRON DEFICIENCYUpdates..• A low hepcidin level in hemodialysis patients with high epoetin resistance index could be a useful marker of iron-restricted erythropoiesis, but confirmation by a therapeutical trial is necessary. Brătescu LO et al, 2010• Iron status should be regularly assessed for the optimal management of renal anemia. Guidelines include the hemoglobin content of reticulocytes and the percentage of hypochromic RBC as markers for functional iron deficiency. European guidelines 14
  15. 15. Target… European Best US Kidney Disease Outcome Quality Practice Initiative Guidelines Target hemoglobin (110( 11.0< (120–110( 12.0–11.0(level, g/dL (g/LFerritin, ng/mL (225( 100< (449( 200< ((pmol/L Transferrin 20< 20≤ (%(saturation %HYPO 10> — (CHret (pg 29< 29< 15
  16. 16. Target…  • Approximately 1000 mg is required among hemodialysis patients to raise hemoglobin levels from approximately 8 g/dL to 11 to 12 g/dL with the initiation of ESA therapy.• After target hemoglobin levels are achieved, approximately 500 mg of iron is required every three months to maintain target levels with ESA therapy. K/DOQI Clinical practice guidelines 16
  17. 17. Target…The Japanese Society for Dialysis Therapy Guidelines 2011•propose that a minimal amount of iron should be given tochronic kidney disease patients with anemia and only in cases ofevident iron deficiency.•Japanese clinicians believe that the risk/benefit ratio for ironsupplementation is higher than that accepted in Westerncountries. 17
  18. 18. Target…The Japanese Society for Dialysis Therapy Guidelines 2011•. When erythropoiesis-stimulating agent hyporesponsivenessexists, we should consider conditions other than iron deficiencyand treat these conditions to improve iron utilization. 18
  19. 19.  EBM•Intravenous sodium ferric gluconate complex in sucroseor iron sucrose rather than iron dextran for hemodialysispatients because of their apparently equivalent efficacybut greater relative safety compared to iron dextran (Grade 1A)•Among hemodialysis patients, the use of parenteral ironrather than oral iron therapy is recommended (Grade 1B) 19
  20. 20.  EBM 125 mg of sodium ferric gluconate complex in sucrose can beIf iron indices indicate absolute given at each consecutive(transferrin saturation <20 hemodialysis treatment for a total ofpercent and the serum ferritin is eight doses (1000 mg in total).<200 ng/mL) or functional irondeficiency (transferrin ORsaturation <20 percent and theserum ferritin is between 200 to 100 mg iron sucrose can be given at500 ng/mL in the setting of ESA each consecutive hemodialysistherapy) treatment for a total of 10 doses (1000 mg in total) (Grade 1B) 20
  21. 21. EBMIntravenous iron is not given to patients with ferritin levels above 500 ng/mLand anemia, although each patient should be individually assessed. (Grade 2B)Among such patients, an initial trial of increased erythropoietin dose alone,without intravenous iron, may be considered if the hemoglobin level ispersistently below 11 g/dL with an erythropoietin dose that is not particularlyhigh. (Grade 2B)If this is not successful in raising the hemoglobin level or a further increase isdesired, we suggest judicious supplemental iron with or without a furtherincrease in erythropoietin dose (Grade 2B) 21
  22. 22. TrendsHD patients had impaired endothelial functions.However, in HD patients, high and repeated doses of IViron sucrose do not have deleterious effects onendothelial functions. Ozkurt S et al, 2012 22
  23. 23.  Trends This formulation, uniquely, can be administered in a large dose asa short intravenous injection of 1 min or less, markedly facilitatingcare. Rosner MH et al, 2011 23
  24. 24. TrendsIn view of the ability of iron to exert direct toxic effects and toinduce oxidative stress on the one hand versus its essential role invarious cellular processes on the other hand, the possible role ofiron in the development of vascular calcification should beconsidered. Neven E et al, 2011 24
  25. 25. TrendsIron sucrose appears to offer the most favorable safety profile whencompared to iron dextran and sodium ferric gluconate in treatinghemodialysis patients. Oxidative stress and hypersensitivityreactions are common problems encountered when administeringintravenous iron. 25 Copol E et al, 2011
  26. 26. TrendsIron isomaltoside 1000 was clinically well tolerated, safeand effective. This new intravenous iron may offer afurther valuable choice in treating the anemia of CKD. Bhandari S et al, 2011 26
  27. 27.  Trends Newly available iron preparations appear to be clinically promising, cost effective, and practical alternatives to current standards of iron repletion Bhandari S 2011 27
  28. 28. THANK YOU 28