ESA dose titration after inadequate initial response

Hemodialysismedium

A 52-year-old woman is evaluated in the dialysis unit to discuss her anemia. Her history includes ESKD secondary to IgA nephropathy, anemia, hyperphosphatemia, well-compensated alcohol-associated liver cirrhosis, and hypertension. She has been receiving in-center HD three times per week for the past 5 months via a brachiocephalic arteriovenous fistula, and she is actively listed for kidney transplantation. A review of systems is only notable for fatigue, and she denies any signs of bleeding. Her medications include carvedilol and sevelamer. Four weeks ago, her hemoglobin was noted to be 6.9 g/dL, and she was prescribed epoetin alfa, 3500 units three times per week. On current examination, BP is 138/72 mm Hg, heart rate is 92/min, and weight is 75 kg. She is somewhat lethargic but able to answer all questions, and the remainder of the examination is unremarkable. Laboratory data (4 weeks ago, current; reference): hemoglobin 6.9, 7.1 g/dL (12–16); transferrin saturation 39%, 35% (20–50); ferritin 920, 725 ng/mL (24–307); serum aspartate aminotransferase 48, 61 U/L (10–40); serum alanine aminotransferase 32, 47 U/L (10–40). Additional laboratory testing, including thyroid function, B₁₂, folate, PTH, and peripheral blood smear are normal. Current single-pool Kt/V is 1.5 (reference range >1.2). Which ONE of the following is the MOST appropriate next step in the management of this patient’s anemia?

  1. A.Change epoetin alfa to daprodustat
  2. B.Transfuse packed red blood cells
  3. C.Prescribe ferric gluconate IV
  4. D.Increase epoetin alfa doseCorrect

Explanation

This patient with ESKD and anemia should be prescribed a higher dose of epoetin alfa. According to KDIGO guidelines, patients with ESKD who have significant anemia and adequate iron stores and no evidence of other reversible causes of anemia should be treated with an erythropoietin-stimulating agent (ESA). This patient was initiated on an appropriate low-dose, weight-based ESA regimen 4 weeks ago but had minimal response. In addition to investigating for causes of initial ESA hyporesponsiveness, the ESA dose can be increased after 4 weeks if the hemoglobin value increases by <1.0 g/dL, as in this case. Daprodustat, a hypoxia-inducible factor inhibitor (HIF inhibitor) is an alternative oral option that may be used in select patients with anemia in ESKD, especially in those with ESA hyporesponsiveness. HIF inhibitors upregulate HIF levels through the inhibition of prolyl hydroxylase activity, which stimulates erythropoietin production and enhances iron metabolism, leading to increased hemoglobin levels. Daprodustat is approved for patients who have been receiving dialysis for at least 4 months. However, the package insert recommends daprodustat not be used in patients with severe hepatic impairment as it has not been studied in that population. Further, the package insert for vadadustat, another HIF inhibtor, states the drug is not recommended in patients with cirrhosis or active, acute liver disease because of signals of hepatotoxicity (<1% of patients). The speculated mechanism is through HIF upregulation hepatic genes that promote steatosis, inflammation, and fibrosis in the liver. Whereas in most patients HIF inhibitors may cause only mild elevation in liver enzymes, caution should be exercised in patients with advanced liver disease in whom the drug effects may be more pronounced. HIF inhibitors should also be avoided in patients with risk of thromboembolic disease, cardiovascular events, pregnancy, malignancy, or prior vascular access thrombosis. IV iron infusion would not be recommended at this time, because this patient’s iron stores are above the recommended ranges for initiating iron IV. KDIGO guidelines recommend that patients with ESKD and anemia should receive iron repletion when transferrin saturation is less than 30% and/or ferritin is less than 500 ng/mL. Blood transfusion should be avoided in advanced CKD and in patients with ESKD and anemia who are awaiting a kidney transplant, to minimize the risk of allosensitization. Although this patient does have significant anemia, no cardiovascular symptoms are present and attempts should first be made to treat the anemia without transfusion.

Why each option

A.
HIF prolyl hydroxylase inhibitors are not recommended in cirrhosis or significant liver disease because of hepatotoxicity signals, and her aminotransferases are rising.
B.
Transfusion risks HLA allosensitization in a transplant-listed patient and should be avoided absent cardiovascular symptoms or active bleeding.
C.
Transferrin saturation 35% and ferritin 725 ng/mL exceed the KDIGO thresholds of 30% and 500 ng/mL for starting intravenous iron.
D.
Correct. A hemoglobin rise under 1.0 g/dL after 4 weeks of ESA with replete iron and no reversible cause warrants increasing the epoetin dose.

Reference: KDIGO 2012 Clinical Practice Guideline for Anemia in CKD; Singh AK, N Engl J Med 2021 (ASCEND-D)

This is one of 1,100 questions in the MedBoardSA nephrology bank, with timed test mode, tutor mode, and progress tracking by topic.

Practise the full bank

More Hemodialysis questions

Browse other topics