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CME

Anemia of Chronic Kidney Disease

General Information

Description

  • hypoproliferative anemia secondary to chronic kidney disease1,3
  • typically normocytic and normochromic unless other conditions present1,3
    • folate or vitamin B12 deficiency may cause macrocytosis
    • iron deficiency or inherited hemoglobin disorders may cause microcytosis
  • associated with high mortality, morbidity, and reduced health-related quality of life (Curr Opin Nephrol Hypertens 2017 May;26(3):214)
  • since the introduction of the first erythropoiesis-stimulating agent epoetin as treatment of anemia, burden of illness has greatly reduced in patients with chronic kidney disease, almost eliminating transfusion-dependent anemia (Kidney Int Suppl (2011) 2017 Dec;7(3):157full-text)

Also Called

  • anemia of renal insufficiency

Definitions

  • World Health Organization (WHO) definition of anemia at sea level
    • hemoglobin < 13 g/dL (130 g/L) in men ≥ 15 years old
    • hemoglobin < 12 g/dL (120 g/L) in nonpregnant women ≥ 15 years old or adolescents aged 12-14 years
    • hemoglobin < 11.5 g/dL (115 g/L) in children aged 5-11 years
    • hemoglobin < 11 g/dL (110 g/L) in pregnant women, or children aged 6-59 months
    • Reference - WHO VMNIS 2011 PDF
  • Kidney Disease Improving Global Outcomes (KDIGO) defines CKD as either of the following for > 3 months
    • glomerular filtration rate (GFR) < 60 mL/minute/1.73 m2
    • kidney damage as evidenced by ≥ 1 of
      • albuminuria
      • urine sediment abnormalities
      • electrolyte or other abnormalities due to tubular disorders
      • abnormal histology
      • abnormal structure detected by imaging
      • history of kidney transplant
      Reference - KDIGO (2011) 2013 CKD evaluation and management Jan PDF
  • CKD staging based on cause, GFR category, and albuminuria category (KDIGO Level 1, Grade B)
    • cause - assignment based on presence or absence of systemic disease and location in the kidney of observed or presumed pathologic-anatomic findings
    • GFR categories
      • G1 - GFR > 90 mL/minute/1.73 m2 (normal or high)
      • G2 - GFR 60-89 mL/minute/1.73 m2 (mildly decreased compared to young adult level)
      • G3a - GFR 45-59 mL/minute/1.73 m2 (mild-to-moderately decreased)
      • G3b - GFR 30-44 mL/minute/1.73 m2 (moderate-to-severely decreased)
      • G4 - GFR 15-29 mL/minute/1.73 m2 (severely decreased)
      • G5 - GFR < 15 mL/minute/1.73 m2 (kidney failure)
    • albuminuria categories
      • A1 - albumin excretion rate (AER) < 30 mg/24 hours, albumin to creatinine ratio (ACR) < 30 mg/g (3 mg/mmol) (normal to mildly increased)
      • A2 - AER 30-300 mg/24 hours, ACR 30-300 mg/g (3-30 mg/mmol) (moderately increased compared to young adult level)
      • A3 - AER > 300 mg/24 hours, ACR > 300 mg/g (30 mg/mmol) (severely increased [including nephrotic syndrome])
    • Reference - KDIGO (2011) 2013 CKD evaluation and management Jan PDF
  • alternative classification system based on combination of estimated GFR and proteinuria
    • risk category 0 - if estimated GFR ≥ 60 mL/minute/1.73 m2 and normal proteinuria
    • risk category 1 - if either
      • estimated GFR 45-59.9 mL/minute/1.73 m2 and normal proteinuria
      • estimated GFR ≥ 60 mL/minute/1.73 m2 and mild proteinuria
    • risk category 2 - if either
      • estimated GFR 45-59.9 mL/minute/1.73 m2 and mild proteinuria present
      • estimated GFR 30-44.9 mL/minute/1.73 m2 and normal proteinuria
    • risk category 3 - if any of the following
      • estimated GFR ≥ 60 mL/minute/1.73 m2 and heavy proteinuria
      • estimated GFR 30-44.9 mL/minute/1.73 m2 and mild proteinuria
      • estimated GFR 15-29.9 mL/minute/1.73 m2 and normal proteinuria
    • risk category 4 - if either
      • estimated GFR 15-29.9 mL/minute/1.73 m2 and mild proteinuria
      • estimated GFR 15-59.9 mL/minute/1.73 m2 and heavy proteinuria
    • alternative staging system would reclassify some patients to lower stage compared to standard staging system using estimated GFR alone
    • Reference - mnh21200034pmdc21200034pAnn Intern Med 2011 Jan 4;154(1):12, editorial can be found in mnh21200043pmdc21200043pAnn Intern Med 2011 Jan 4;154(1):65
  • iron deficiency anemia
    • iron deficiency that has progressed to iron-deficient erythropoiesis and anemia (N Engl J Med 2015 May 7;372(19):1832, commentary can be found in N Engl J Med 2015 Jul 30;373(5):484)
    • can be classified as4
      • absolute - total body iron stores are low or absent
      • functional
        • state of iron-poor erythropoiesis resulting from impaired or insufficient mobilization and delivery of iron to erythroid precursors despite normal or increased total body iron stores (defined by the presence of stainable iron in the bone marrow plus serum ferritin value within normal limit)
        • may occur in patients with chronic kidney disease receiving erythropoiesis-stimulating agents, due to increased demands for iron
      • References - Lancet 2016 Feb 27;387(10021):907

References

General references used

  1. Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline for anemia in chronic kidney disease. KDIGO 2012 Aug PDF
  2. Mikhail A, Brown C, Williams JA, et al. Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease. BMC Nephrol. 2017 Nov 30;18(1):345full-text
  3. Babitt JL, Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol. 2012 Oct;23(10):1631-4full-text
  4. Thomas DW, Hinchliffe RF, Briggs C, et al., British Committee for Standards in Haematology. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013 Jun;161(5):639-48

Recommendation grading systems used

  • British Committee for Standards in Haematology (BCSH) guideline grading system
    • strength of recommendation
      • Grade 1 - strong recommendations made when there is confidence that benefits do or do not outweigh harm and burden, can be applied uniformly to most patients, regard as "recommend"
      • Grade 2 - weak recommendations made where benefits and risks and burdens are closely balanced or magnitude of benefits and risks is less certain, require judicious application to individual patients based on patient values and preferences, regard as "suggest"
    • quality of evidence
      • A - high; further research very unlikely to change confidence in estimate of effect, based on randomized trials without important limitations
      • B - moderate; further research may well have important impact on confidence in estimate of effect and may change estimate, based on randomized trials with important limitations or very strong evidence from observational studies
      • C - low; further research likely to have important impact on confidence in estimate of effect and likely to change estimate, based on observational studies
      • D - very low; any estimate of effect is very uncertain, based on any other evidence
    • References
  • Kidney Disease Improving Global Outcomes (KDIGO) rating guideline recommendations
    • strength of recommendation
      • Level 1 ("we recommend") - most patients should receive recommended course of action
      • Level 2 ("we suggest") - different choices will be appropriate for different patients, based on patient's values and preferences
      • Not Graded - topic does not allow adequate application of evidence, not meant to be interpreted as being stronger recommendations than Level 1 or 2
    • quality of evidence
      • Grade A - high-quality evidence, true effect lies close to that of estimate of effect
      • Grade B - moderate-quality evidence, true effect likely to be close to estimate of effect, but there is a possibility it is substantially different
      • Grade C - low-quality evidence, true effect may be substantially different from estimate of effect
      • Grade D - very low-quality evidence, estimate of effect very uncertain and often far from the truth
    • Reference - KDIGO clinical practice guideline on anemia in chronic kidney disease (KDIGO 2012 Aug PDF)
  • Renal Association (RA) uses the modified GRADE system to indicate strength of recommendation and level of evidence for recommendation
    • recommendation
      • Grade 1 - strong recommendation, desirable effects of the intervention clearly outweigh the undesirable effects
      • Grade 2 - weak recommendation, desirable effects will outweigh the undesirable effects, but no confidence in the trade-offs because key evidence is of low quality or the benefits and downsides are closely balanced
      • Not Graded - topic does not allow adequate application of evidence, not meant to be interpreted as being stronger recommendations than Level 1 or 2
    • level of evidence
      • Grade A - high, further research very unlikely to change confidence in the estimate of effect
      • Grade B - moderate, research likely to have an important impact on confidence in the estimate of effect and may change the estimate
      • Grade C - low, further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate
      • Grade D - very low, any estimate of effect is uncertain
    • PubMed29191165BMC nephrologyBMC Nephrol20171130181345345Reference - RA clinical practice guideline on anemia of chronic kidney disease (BMC Nephrol 2017 Nov 30;18(1):345full-text)

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How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T905401, Anemia of Chronic Kidney Disease; [updated 2018 Dec 04, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T905401. Registration and login required.

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