What are the guideline sources, guidelines and references for Anemia of chronic kidney disease ?
Guideline sources The following summarized guidelines for the evaluation and management of anemia of chronic kidney disease are prepared by our editorial team based on guidelines from the Japanese Society of Nephrology (JSN 2019), the United Kingdom Kidney Association (UKKA 2017), the British Committee for Standards In Haematology (BCSH 2013), and the Kidney Disease: Improving Global Outcomes Foundation (KDIGO 2012). 1 2 3 4 5 6 6 7 Definition Anemia of CKD is usually normocytic, normochromic, and hypoproliferative, which increases as the kidney disease progresses. 5 Epidemiology Anemia of CKD is mostly caused by a relative deficiency in EPO (EPO) production. Other causes include inflammation, iron deficiency, and accumulation of uremic toxins. 6 Disease course Decreased production of EPO due to worsening kidney function results in anemia of CKD, which causes clinical manifestations of decreased quality of life, cognitive impairment, sleep disturbances, CKD progression, and cardiovascular comorbidities. 6 https://web.pathway.md/diseases/recj8yk723oBn05WO 1/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway Prognosis and risk of recurrence Anemia of CKD among diabetics is associated with higher mortality (HR 3.61, 95% CI 2.48-5.26). 7 Guidelines 1. Screening and diagnosis Indications for screening: As per UKKA 2017 guidelines, consider measuring Hgb levels at least at following intervals to screen for anemia in patients with CKD: stage 3: once per year stage 4-5, non-dialysis: twice per year. C As per KDIGO 2012 guidelines, measure Hgb concentration in patients with CKD without anemia when clinically indicated and at least at the following intervals according to the stage of CKD: Situation Guidance Once per year Stage 3 Twice per year Stage 4-5, non-dialysis Every 3 months. Stage 5, on hemodialysis or peritoneal dialysis Diagnostic criteria: As per UKKA 2017 guidelines, suspect CKD as a possible cause of anemia when the GFR is < 60 mL/min/1.73m , especially if < 30 mL/min/1.73m (or < 45 mL/min/1.73m in patients with diabetes) and no other cause such as blood loss, folic acid or vitamin B12 deficiency is identified. B As per KDIGO 2012 guidelines: Diagnose anemia in 15 years old adolescent and adult patients with CKD based on the Hgb concentration < 13.0 g/dL in males and < 12.0 g/dL in females. Diagnose anemia in < 15 years old pediatric patients with CKD based on the age group- specific Hgb concentration: Situation Guidance < 11.0 g/dL 0.5-5 years < 11.5 g/dL 5-12 years https://web.pathway.md/diseases/recj8yk723oBn05WO 2/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway 12-15 years < 12.0 g/dL. 2. Diagnostic investigations Initial evaluation: As per UKKA 2017 guidelines, evaluate all patients with chronic anemia associated with CKD for the cause and possible treatment in case of Hgb levels < 110 g/L (< 105 g/L in patients aged < 2 years) or symptoms attributable to anemia, irrespective of the grade of kidney disease or requirement for RRT. A Show 4 more As per KDIGO 2012 guidelines, obtain the following tests as part of the initial evaluation of anemia in patients with CKD, regardless of age and CKD stage: CBC absolute reticulocyte count serum ferritin level serum transferrin saturation serum vitamin B12 and folate levels. Erythropoietin measurement: avoid obtaining routine measurements of EPO levels for the diagnosis or management of anemia in patients with CKD. D Evaluation for functional iron deficiency: measure mean cell volume and mean cell Hgb values at diagnosis of iron deficiency and for assessing trends over periods of weeks or months, but not for assessing acute changes in iron availability secondary to therapy with ESAs. B Show 9 more 3. Medical management Iron therapy: As per JSN 2019 guidelines, consider administering iron therapy in patients with CKD and iron deficiency anemia. C As per UKKA 2017 guidelines, ensure iron repletion (defined as a percentage of hypochromic RBCs < 6%, reticulocyte Hgb count > 29 pg, ferritin > 100 g/L, and transferrin saturation > 20%) to achieve and maintain target Hgb whether receiving ESAs or not. B Show 6 more As per KDIGO 2012 guidelines, balance the potential benefits of iron therapy (avoiding or minimizing blood transfusions, ESA therapy, and anemia-related symptoms) against potential risks of harm (anaphylactoid reactions, other unknown long-term risks) when prescribing iron therapy. Show 7 more https://web.pathway.md/diseases/recj8yk723oBn05WO 3/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway Erythropoiesis-stimulating agents, initiation: As per UKKA 2017 guidelines, initiate ESAs in patients with anemia of CKD likely to benefit in terms of quality of life and physical function and to avoid blood transfusion, especially in patients deemed suitable for transplantation. B Show 2 more As per KDIGO 2012 guidelines, address all correctable causes of anemia including iron de ciency and in ammatory states before initiating ESAs. Show 6 more Erythropoiesis-stimulating agents, choice of agent: As per UKKA 2017 guidelines, decide on the choice of ESAs based on the local availability of ESAs. B As per KDIGO 2012 guidelines: Decide on the choice of an ESA based on the balance of pharmacodynamics, safety information, clinical outcome data, costs, and availability. B Consider choosing only ESAs approved by an independent regulatory agency. Choose true biosimilar products for 'copy' versions of ESAs. C Erythropoiesis-stimulating agents, route of administration: As per UKKA 2017 guidelines, consider determining the route of ESA administration by the CKD grade, treatment setting, efficacy, safety and class of ESA used. Prefer the SC route in non- dialysis patients and the IV route in hemodialysis patients because of convenience. C As per KDIGO 2012 guidelines: Consider using either IV or SC route of administration of ESAs in patients with CKD stage 5 on hemodialysis and in patients on hemofiltration or hemodia ltration therapy. C Consider using the SC route of administration of ESAs in patients with non-dialysis CKD and in patients with CKD stage 5 on peritoneal dialysis. C Erythropoiesis-stimulating agents, dosing: As per UKKA 2017 guidelines, determine the initial ESA dose based on the patient's Hgb level, target Hgb level, the observed rate of increase in Hgb level, and clinical circumstances. B Show 2 more As per KDIGO 2012 guidelines, determine the initial ESA dose based on the patient's Hgb concentration, body weight, and clinical circumstances. B Show 4 more Erythropoiesis-stimulating agents, maintenance: As per JSN 2019 guidelines, consider reducing or terminating ESAs if the Hgb level is > 12 g/dL in patients with a past history or complication of severe CVD or any other medical indications. C As per UKKA 2017 guidelines, continue ESA therapy during acute illness, surgical procedures, or any other cause of hospitalization in ESA-dependent patients unless there is a clear contraindication, such as accelerated hypertension. B https://web.pathway.md/diseases/recj8yk723oBn05WO 4/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway Landmark trials: CHOIR In patients with anemia of CKD, high-Hgb was inferior to low-Hgb with respect to death, myocardial infarction, hospitalization for congestive HF, or stroke Singh AK et al. N Engl J Med. 2006 Nov 16. As per KDIGO 2012 guidelines, avoid using ESAs to maintain Hgb concentration > 11.5 g/dL in adult patients with CKD. D Show 2 more Treatment targets: As per JSN 2019 guidelines, target Hgb levels of 11 g/dL and < 13 g/dL for ESA use in patients with non-dialysis CKD. B As per UKKA 2017 guidelines: Do not exceed serum ferritin level > 800 g/L in patients treated with iron therapy and review treatment when ferritin level is > 500 g/L. D Consider achieving Hgb targets of 100-120 g/L in adult patients (and pediatric patients aged > 2 years) with CKD on ESA therapy. C Adjuvant therapies: Do not use androgens as an adjuvant to ESAs. D Avoid using vitamin C, vitamin D, vitamin E, folic acid, L-carnitine, and pentoxifylline as adjuvants to ESAs. D 4. Therapeutic procedures Red blood cell transfusion: As per UKKA 2017 guidelines, avoid administering RBC transfusion where possible to minimize the risk of allosensitisation in patients with anemia of CKD, especially if renal transplantation is an option. D Show 2 more As per KDIGO 2012 guidelines, avoid administering red cell transfusions when possible to minimize the general risks related to their use when managing chronic anemia. D Show 4 more 5. Specific circumstances Pediatric patients (iron therapy): Administer oral iron (or IV iron in patients with hemodialysis-dependent CKD) when transferrin saturation is < 20% and ferritin is < 100 ng/mL in pediatric patients with anemia of CKD not on iron or ESA therapy. B https://web.pathway.md/diseases/recj8yk723oBn05WO 5/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway Administer oral iron (or IV iron in patients with hemodialysis-dependent CKD) to maintain transferrin saturation > 20% and ferritin > 100 ng/mL in pediatric patients with CKD on ESA therapy not receiving iron therapy. B Pediatric patients, ESA therapy: As per UKKA 2017 guidelines: Consider adjusting ESA doses when Hgb is < 105 or > 115 g/L in 2 years old pediatric patients to balance the benefit and safety to patients. Do not wait until Hgb levels are outside the aspirational range before adjusting treatment, instead take action when Hgb levels are within 5 g/L of the range's limits to keep the Hgb level within the aspirational range in < 2 years old pediatric patients. As per KDIGO 2012 guidelines, balance potential bene ts (improvement in quality of life, school attendance/performance, and avoidance of transfusion) against potential harms when selecting Hgb concentration for ESA therapy initiating in individual patients with CKD. B Pediatric patients, treatment targets: As per UKKA 2017 guidelines, aim for a target ferritin level > 100 g/L in pediatric patients with dialysis-dependent CKD and in patients with CKD not receiving ESA therapy. As per KDIGO 2012 guidelines, consider targeting Hgb concentration in the range of 11.0-12.0 g/dL in pediatric patients with CKD receiving ESA therapy. C Renal transplant recipients: treat anemia in renal transplant patients similar to patients with non- dialysis CKD. B Patients with ESA-induced PRCA: As per UKKA 2017 guidelines, do not obtain routine screening for anti-EPO antibodies in patients with CKD regularly treated with ESAs. D Show 3 more As per KDIGO 2012 guidelines, evaluate for possible antibody-mediated pure red cell aplasia in patients receiving ESAs for > 8 weeks and developing all of the following: sudden rapid decrease in Hgb concentration (at the rate of 0.5-1.0 g/dL per week, or requirement for transfusions at the rate of approximately 1-2 per week) normal platelet and white cell counts absolute reticulocyte count < 10, 000/mL. Show 2 more 6. Follow-up and surveillance Serial hemoglobin monitoring (patients not on ESA therapy): Measure Hgb concentration in patients with anemia of CKD when clinically indicated and at least at the following intervals according to the stage of CKD: stage 3-5, non-dialysis or peritoneal dialysis: every 3 months stage 5, on hemodialysis: every month. https://web.pathway.md/diseases/recj8yk723oBn05WO 6/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway Serial hemoglobin monitoring, patients on ESA therapy: As per UKKA 2017 guidelines: Consider monitoring Hgb concentration every 2-4 weeks in the correction phase and every 1-3 months in stable patients in the maintenance phase. C Consider obtaining more frequent monitoring depending on clinical circumstances. C As per KDIGO 2012 guidelines, measure Hgb concentration at least monthly during the initiation phase of ESA therapy. Show 2 more Serial iron status monitoring: As per UKKA 2017 guidelines, monitor iron status every 1-3 months in patients receiving IV iron to avoid toxicity. B Consider viewing serum ferritin consistently > 800 g/L with no evidence of inflammation, such as normal CRP, as suggestive of iron overload. B As per KDIGO 2012 guidelines: Obtain serum ferritin and transferrin saturation to assess iron status at least every 3 months during ESA therapy, and initiate or continue iron therapy accordingly. Assess iron status (ferritin and transferrin saturation) more frequently when initiating or increasing ESA dose, when there is blood loss, when monitoring response after a course of IV iron, and in other circumstances where iron stores may become depleted. Serial blood pressure monitoring: monitor BP in all patients receiving ESAs and, treat hypertension, if present, by volume removal and/or antihypertensive drugs. A Management of ESA hyporesponsiveness: As per JSN 2019 guidelines, determine and correct the causes of ESA hyporesponsiveness. Avoid overdosing ESAs. B As per UKKA 2017 guidelines: Define inadequate response ('resistance') to ESA therapy as failure to reach the target Hgb level despite SC epoetin dose > 300 IU/kg/week (450 IU/kg/week IV epoetin) or darbepoetin dose > 1.5 g/kg/week. A Obtain clinical assessment and evaluation for other common causes of anemia in patients with hyporesponsiveness with iron repletion. A As per KDIGO 2012 guidelines, classify patients as having ESA hyporesponsiveness if there is no increase in Hgb concentration from baseline after the first month of ESA treatment at appropriate weight-based dosing. Show 5 more References 1. KDIGO Executive Committee. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. KDIGO. 2012 Aug. Open https://web.pathway.md/diseases/recj8yk723oBn05WO 7/8 6/23/23, 2:35 AM Anemia of chronic kidney disease Pathway 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 1 345. Open 3. Japanese Society of Nephrology. Essential points from Evidence-based Clinical Practice Guidelines for Chronic Kidney Disease 2018. Clin Exp Nephrol. 2019 Jan;23 1 1 15. Open 4. Thomas DW, Hinchliffe RF, Briggs C et al. Guideline for the laboratory diagnosis of functional iron deficiency. Br J Haematol. 2013 Jun;161 5 639 48. Open 5. Jodie L Babitt, Herbert Y Lin. Mechanisms of anemia in CKD. 2012 Oct;23 10 1631 4.2012 Oct;23 10 1631 4. Open 6. Melissa E Stauffer, Tao Fan. Prevalence of anemia in chronic kidney disease in the United States. 2014 Jan 2;9 1):e84943.2014 Jan 2;9 1):e84943. Open 7. C Yang, J W Wang, Y Z Yang et al. Impact of anemia and chronic kidney disease on the risk of cardiovascular disease and all-cause mortality among diabetic patients]. 2018 Jun 18;50 3 495 500.2018 Jun 18;50 3 495 500. 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