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Anemia in kidney disease
- 1. Evaluation & diagnostic approach to anemia with kidney disease Dr. B.Dormanesh
- 2. 2 often no symptoms High BP proteinuria anemia early bone dis. fatigue , swelling Nausea , ……. needs renal replacement therapy In patients with CKD but stable kidney function, the appearance or progression of anemia may herald a new problem that is causing blood loss or is interfering with red cell production.
- 3. 3 Anemia is a condition in which the number of RBCs or their oxygen-carrying capacity is insufficient to meet physiologic needs, which vary by age, sex
- 4. 4 How to define anemia in CKD KDIGO 2012 Clinical Practice Guideline for Anemia in Chronic Kidney Disease In adults and children >15 years with CKD (Not Graded) Hb<13.0 g/dl in males Hb<12.0 g/dl in females In children with CKD (Not Graded) Hb<11.0 g/dl in children 0.5–5 years Hb< 11.5 g/dl in children 5–12 years Hb< 12.0 g/dl in children 12–15 years
- 5. Frequency of testing for anemia in CKD 5KDIGO 2012 Clinical Practice Guideline for Anemia in Chronic Kidney Disease CKD adults without anemia measure Hb concentration when clinically indicated (Not Graded) at least annually in patients with CKD 3 at least twice per year in patients with CKD 4–5ND at least every 3 months in patients with CKD 5HD and CKD 5PD
- 6. Frequency of testing for anemia in CKD 6KDIGO 2012 Clinical Practice Guideline for Anemia in Chronic Kidney Disease CKD children with anemia not being treated with an ESA measure Hb concentration when clinically indicated (Not Graded) at least every 3 months in patients with CKD 3–5ND and CKD 5PD at least monthly in patients with CKD 5HD
- 7. 7Hemoglobin decline in children with CKD ,Clin J Am Soc Nephrol 2008; 3: 457–462. GFR ≅43ml/min /1.73m2
- 8. Frequency of testing for anemia in CKD 8 CKD patients being treated with ESA in the initiation phase of ESA therapy, at least monthly. (Not Graded) for CKD ND patients, during the maintenance phase of ESA therapy , at least every 3 months. (Not Graded) for CKD 5D patients, during the maintenance phase of ESA therapy, at least monthly KDIGO 2012 Clinical Practice Guideline for Anemia in Chronic Kidney Disease
- 9. Investigation of anemia in CKD 9 In patients with CKD and anemia (regardless of age and CKD stage), include the following tests in initial evaluation of anemia : CBC (Hb , red cell indices, WBC ( diff) & platelet count) Absolute reticulocyte count Serum ferritin level Serum transferrin saturation (TSAT) Serum vitamin B12 and folate levels KDIGO 2012 Clinical Practice Guideline for Anemia in Chronic Kidney Disease
- 10. CBC 10 Hollowell JG, van Assendelft OW, Gunter EW et al. Hematological & iron-related analytes–reference data for persons aged 1 year and over: US , 1988-94. Vital Health Stat 11, 2005, 1–156. Nathan and Oski’s Hematology of Infancy and Childhood, 6th edn. WB Saunders: Philadelphia, PA, 2003, p 1841.
- 11. 11 Absolute reticulocyte count Effective erythropoietic proliferative activity is most simply assessed by determination of the absolute reticulocyte count . which may be high in patients who have active blood loss or hemolysis low in hypoproliferative erythropoiesis with anemia in CKD
- 12. 12 Iron storage Ferritin is the most commonly used test ( not gold standard ) - acute phase reactant - Ferritin value TSAT is the most commonly used for availability of iron to support erythropoiesis. Other tests of iron status Sensitivity and specificity of TSAT and serum ferritin & their combination & also BM iron to identify correctly a positive erythropoietic response (≥1-g/dl increase in Hb ) to intravenous iron in 100 NHD patients with CKD J Am Soc Nephrol 2010; 5: 409–416
- 13. 13 Vitamin B12 & Folate Uncommon but important causes of easily correctable anemia prevalence 10% in HD patients but unknown prevalence in CKD patients Folate deficiency detection methods
- 14. 14 Additional tests may be appropriate in individual patients and in certain specific clinical settings. CRP may be indicated if occult inflammation is a concern. In certain countries and/or in patients of specific nationalities or ethnicities, testing for hemoglobinopathies, parasites, and ,…..
- 15. Anemia & kidney 15 Infections such as UTI Renal cysts Nephritic syndrome Renal stones & hematuria Reflux-Related Renal Injury ??? Nephrotic syndrome Anemia in nephrotic syndrome: approach to evaluation and treatment. Pediatr Nephrol. 2017 Aug;32(8):1323-1330
- 16. تشکر با باشید موفق و شاد 16
Editor's Notes
- (World Health Organization. Worldwide Prevalence of Anaemia 1993–2005: WHO Global Database on Anaemia. In: de Benoist B, McLean E, Egli I and M Cogswell (eds), 2008.)
- Clinically indicated means also such as after a major surgical procedure, hospitalization, or bleeding episode.
- Clinically indicated means also such as after a major surgical procedure, hospitalization, or bleeding episode.
- Children Prospective Cohort Study (CKiD), which evaluated 340 North American children with CKD using iohexol determined GFR ,in the GFR <43 ml/min per 1.73m2, there was a linear relationship between Hb and GFR, with Hb 0.3 g/dl (3 g/l) lower per 5 ml/min per 1.73m2 lower GFR. Above that threshold, there was a non significant association of 0.1 g/dl (1 g/l) lower Hb for every 5 ml/min per 1.73m2 lower GFR. (Fadrowski JJ, Pierce CB, Cole SR et al. Hemoglobin decline in children with chronic kidney disease: baseline results from the chronic kidney disease in children prospective cohort study. Clin J Am Soc Nephrol 2008; 3: 457–462.) Because serum creatinine-based estimated glomerular filtration rate (eGFR) using the Schwartz formula may overestimate the true GFR in the children providers need to consider the potential for Hb decline and anemia even at early stages of CKD and monitor accordingly.(Schwartz GJ, Munoz A, Schneider MF et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20: 629–637.)
- ESA = Erythropoiesis-stimulating agent
- Severity of anemia is assessed best by measuring Hb concentration rather than hematocrit. Red cell indexes : Hypoproliferative, and in general, normochromic and normocytic anemia Macrocytosis in Folate or vitamin B12 deficiencies Microcytosis in Iron deficiency or inherited disorders of Hb formation (e.g., a- or b-thalassemia . Note : Iron deficiency, especially if longstanding, is associated with hypochromia (low MCH) Note : hematopoiesis caused by toxins (e.g., alcohol), nutritional deficit (vitamin B12 or folate deficiency), or myelodysplasia. WBC & Platelets : Macrocytosis with leukopenia or thrombocytopenia suggests a generalized disorder
- Note : There are two important and distinct aspects of the assessment of iron status testing: the presence or absence of storage iron and the availability of iron to support ongoing erythropoiesis ‘gold standard’ remains examination of a bone marrow aspiration stained for iron. TSAT = serum iron × 100 divided by total iron binding capacity Ferritin is affected by inflammation and is an ‘acute phase reactant’ so , ferritin values have to be interpreted with caution in CKD patients, especially those on dialysis in whom subclinical inflammation may be present and we know iron can deposit in liver in hepatitis C virus infection Ferritin values ≤30 ng/ml (≤30 mg/l) indicate severe iron deficiency and are highly predictive of absent iron stores in bone marrow. Ferritin values >30 ng/ml (>30 mg/l), however, do not necessarily indicate the presence of normal or adequate bone marrow iron stores. Studies assessing ferritin levels above which all or nearly all patients with CKD have normal bone marrow iron stores have produced varied results but most CKD patients, including those who are on HD, will have normal bone marrow iron stores when their serum ferritin level is ≥300 ng/ml (≥300 mg/l). Even at serum ferritin levels of 100 ng/ml (100 mg/l) most CKD patients have stainable bone marrow iron stores. So the serum ferritin and TSAT values are often used together to assess iron status, diagnose iron deficiency, and predict an erythropoietic response to iron supplementation Other tests of iron status, such as percentage of hypochromic red blood cells and reticulocyte Hb content may be used instead of, or in addition to, TSAT and ferritin levels if available. Measurement of hepcidin levels has not been shown to be clinically useful or superior to more standard iron status tests in patients with CKD supplemental iron should be administered to maintain ferritin levels < 200 ng/ml (< 200mg/l) in CKD 5HD patients and< 100 ng/ml (< 100mg/l) in CKD ND and CKD 5PD with TSAT< 20% in all CKD patients. Evaluate iron status (TSAT and ferritin) at leastevery 3 months during ESA therapy, including thedecision to start or continue iron therapy. (NotGraded)
- assessment are generally considered standard components of anemia evaluation, especially in the presence of macrocytosis. Folate deficiency is best detected in most patients with serum folate level testing; RBC folate levels can be measured when serum folate levels are equivocalor when there is concern that recent dietary intake may obscure underlying folate deficiency using serum levels alone
- Guide subsequent iron administration in CKD patients based on Hb responses to recent iron therapy, as well as ongoing blood losses, iron status tests (TSAT and ferritin), Hb concentration, ESA responsiveness and ESA dose in ESA treated patients, trends in each parameter, and the patient’s clinical status. (Not Graded)
- excessive urinary losses of iron, transferrin, erythropoietin, transcobalamin and/or metals. This leads to a deficiency of substrates necessary for effective erythropoiesis, requiring supplementation in order to correct the anemia. Supplementation of iron and erythropoietin alone often does not lead to correction of the anemia, suggesting other possible mechanisms which need further investigation.