Chronic Kidney Disease (CKD) – Management of Anemia (Lecture III)

100 Question-and-Answer flashcards covering etiology, diagnosis, lab interpretation, and pharmacologic management of anemia in chronic kidney disease, aligned with KDIGO guidelines and lecture content.

What are the two primary categories of anemia encountered in CKD patients?

Iron-deficiency anemia and anemia of chronic disease (anemia of CKD).

Name two first-line pharmacologic options for treating absolute iron-deficiency in CKD.

Oral iron supplementation and intravenous (IV) iron therapy.

Which treatment options address anemia of CKD caused by inadequate erythropoietin production?

Erythropoiesis-stimulating agents (ESAs) and, more recently, hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs).

At what hemoglobin (Hgb) level is an RBC transfusion generally reserved in CKD patients?

When Hgb is less than 7 g/dL in acute or severe anemia.

List three common causes of iron deficiency in CKD.

1) Blood loss from laboratory testing or hemodialysis, 2) reduced intestinal iron absorption (elevated hepcidin, PPIs, calcium binders), 3) decreased dietary intake due to poor appetite or malnutrition.

Which hormone’s decreased production is a major contributor to anemia of chronic disease in CKD?

Erythropoietin.

What role does hepcidin play in CKD-related anemia?

Elevated hepcidin reduces iron release from body stores and decreases intestinal iron absorption, limiting iron availability for erythropoiesis.

Normal hemoglobin range for adult males is _ g/dL.

14–17 g/dL.

Normal hemoglobin range for adult females is _ g/dL.

12–15 g/dL.

What hematology parameter provides an indirect estimate of iron availability and is calculated as (Serum Fe / TIBC) × 100 %?

Transferrin saturation (Tsat).

Microcytic anemia is suggested when the mean corpuscular volume (MCV) is .

Below the normal range of 80–90.6 µm³.

In absolute iron-deficiency anemia, ferritin is typically .

Decreased (low).

In anemia of chronic disease, the usual pattern for ferritin is or .

Normal or increased (because ferritin is an acute-phase reactant).

According to KDIGO 2012, iron therapy should be considered when Tsat is ≤ % AND ferritin is ≤ ng/mL.

Tsat ≤ 30 % and ferritin ≤ 500 ng/mL.

Why is IV iron preferred over oral iron in most CKD patients receiving hemodialysis?

Because oral absorption is limited and dialysis provides immediate venous access for IV administration.

For non-dialysis CKD patients, what is the recommended initial route of iron supplementation?

Oral iron, unless goals are unmet after 1–3 months.

List four commonly prescribed oral iron salts and their approximate % elemental iron content.

Ferrous sulfate (20 %), ferrous gluconate (12 %), ferrous fumarate (33 %), iron polysaccharide (≈ 100 %).

What total daily elemental iron target (in mg) is traditionally recommended for oral therapy, divided into 2–3 doses?

150–200 mg elemental iron per day.

Newer evidence suggests that (frequency) oral iron dosing is equally effective and reduces GI adverse effects.

Every-other-day (QOD) dosing.

Name two prescription-only oral iron products.

Ferric maltol (Accrufer) and ferric citrate (Auryxia).

What common GI adverse effects are associated with oral iron therapy?

Nausea, constipation, abdominal pain, and darkened stools.

How does vitamin C affect oral iron absorption?

Vitamin C increases acidic gastric environment, enhancing iron absorption.

Give two examples of medications that impair oral iron absorption by raising gastric pH.

Proton-pump inhibitors (PPIs) and H2-receptor antagonists.

Why should quinolone or tetracycline antibiotics be separated from oral iron by at least 2 hours?

Because iron chelates with these antibiotics, reducing absorption of both agents.

Name four IV iron formulations commonly used in CKD.

Iron sucrose (Venofer), ferric gluconate (Ferrlicit), ferric carboxymaltose (Injectafer), and ferumoxytol (Feraheme).

Which IV iron product can interfere with MRI results for up to three months?

Ferumoxytol (Feraheme).

What serious but rare hypersensitivity reaction is listed for IV iron therapies?

Anaphylaxis.

State the FDA-recommended epoetin alfa starting dose range for dialysis patients.

50–100 units/kg IV or SQ three times weekly.

When treating CKD-ND (non-dialysis) patients, epoetin alfa is often started at units every week or units every other week.

50–100 units/kg weekly OR 10,000–20,000 units every other week.

Which route of ESA administration is preferred for CKD Stage 5 on hemodialysis (CKD-5HD)?

Intravenous (IV).

Which route is usually preferred for CKD patients not on dialysis (CKD-ND) or on peritoneal dialysis (PD)?

Subcutaneous (SQ).

Name two longer-acting ESA formulations that permit dosing every 2–4 weeks.

Darbepoetin alfa (Aranesp) and methoxy-PEG-epoetin beta (Mircera).

How often should ESA dose increases be made, at minimum, according to general guidelines?

No more frequently than once every 4 weeks.

If hemoglobin rises by more than 1 g/dL in two weeks, what general ESA dose adjustment is recommended?

Reduce the ESA dose by approximately 25 % (or hold if needed).

What hemoglobin threshold should prompt holding the ESA entirely?

Hgb > 13 g/dL.

If hemoglobin fails to increase > 1 g/dL after 4 weeks of ESA therapy, what action should be taken?

Increase the ESA dose by roughly 25 %, provided other causes have been ruled out.

List three serious adverse outcomes highlighted in the FDA boxed warning for all ESAs.

Increased risk of death, myocardial infarction (MI), and stroke (also VTE and vascular access thrombosis).

Name two contraindications to ESA therapy.

Uncontrolled hypertension and history of pure red cell aplasia (PRCA).

KDIGO 2012 recommends initiating ESA in CKD-ND when hemoglobin is below g/dL.

10 g/dL.

In CKD Stage 5 on dialysis, ESA is usually initiated when hemoglobin falls to – g/dL.

9–10 g/dL.

What is the typical hemoglobin target range once on ESA therapy, according to KDIGO?

10–11.5 g/dL.

Why should hemoglobin targets above 13 g/dL be avoided in ESA-treated CKD patients?

Because they are associated with higher risks of CV events and mortality.

How frequently should hemoglobin be monitored during ESA initiation?

At least monthly.

After hemoglobin stabilizes, CKD-ND patients may have Hgb monitored every months, whereas CKD-5D patients remain on monitoring.

Every 3 months; monthly monitoring for CKD-5D.

Vadadustat (Vafseo) belongs to which new drug class for anemia of CKD?

Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs).

What year did the FDA approve vadadustat for anemia management in dialysis patients?

2024.

Briefly describe the mechanism of action of HIF-PHIs.

They inhibit prolyl-hydroxylase, stabilizing HIF-α, which leads to increased erythropoiesis and reduced hepcidin.

State the usual vadadustat oral daily dosage range.

150–600 mg once daily, titrated to Hgb response.

Can vadadustat be co-administered with an ESA?

No; HIF-PHIs are alternatives and should NOT be used concurrently with ESAs.

Like ESAs, vadadustat carries a boxed warning for what major risks?

Increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access.

Which common condition excludes patients from starting either an ESA or a HIF-PHI?

Uncontrolled hypertension.

In the inpatient setting, why should changes to iron or ESA therapy in a CKD-5D patient be discussed with nephrology?

Because anemia management protocols and target Hgb values can vary between institutions and dialysis centers.

Case 1: A HD patient with ferritin 9 ng/mL and Tsat 7.7 % has an active intra-abdominal infection. What is the best iron recommendation?

Do NOT administer IV iron at this time (postpone iron therapy until infection resolves).

Case 1 (alternate): Why is IV iron generally avoided during active systemic infection?

Because IV iron may potentiate bacterial growth and worsen infection.

Case 2: A CKD Stage IV patient on epoetin with Hgb ≈ 9 g/dL, ferritin 255 ng/mL, Tsat 15 %. What is the most appropriate intervention?

Start oral ferrous sulfate (iron supplementation).

Case 3: HD patient on darbepoietin has Hgb 10.5 g/dL. What should be done to ESA dosing?

Continue darbepoietin at the same dose (no change).

Case 4: For a 64 kg woman starting epoetin alfa-epbx on HD, calculate a starting dose using 50 units/kg TIW.

Approximately 3,200 units IV three times weekly (often rounded to the nearest vial size, e.g., 3,000 units).

Case 5: Which ESA boxed-warning risks apply to Epogen? (Select all that apply.)

Increased risk of death, increased risk of venous thromboembolism, increased risk of cancer recurrence.

True or False: Anaphylaxis is part of the ESA boxed warning.

False (anaphylaxis is rare with IV iron, not the primary ESA boxed warning).

Name two laboratory parameters that must be assessed before increasing an ESA dose.

Current hemoglobin level and iron indices (Ferritin/Tsat).

Reticulocyte count reflects _ production and helps determine marrow response.

Red blood cell (RBC).

High MCV values (> 90.6 µm³) point toward anemia.

Macrocytic.

Low MCV values (< 80 µm³) suggest anemia.

Microcytic.

What is the normal transferrin saturation (Tsat) range in adults?

30–50 %.

Ferritin acts as both an iron-storage protein and an _ phase reactant.

Acute.

Oral iron absorption is maximized when taken on an _ stomach.

Empty.

Name a phosphate binder that can reduce oral iron absorption if taken simultaneously.

Sevelamer or calcium-containing binders.

What is the major adverse hemodynamic reaction that may occur during IV iron infusion?

Hypotension or syncope (often rate-related).

Which IV iron formulation requires a test dose when administered as iron dextran?

INOFeD (iron dextran) due to historical anaphylaxis risk.

List two reasons iron polysaccharide or carbonyl iron might be chosen instead of ferrous sulfate.

Higher elemental iron per tablet and potentially fewer GI side effects.

What counseling point explains the dark coloration of stool with oral iron therapy?

Unabsorbed iron oxidizes in the GI tract, turning stools dark or black.

True or False: Food increases the absorption of ferrous sulfate.

False – Food decreases iron absorption, although it can lessen GI upset.

How long should bisphosphonates be separated from oral iron to avoid interaction?

At least 2 hours.

Regular monitoring of iron indices in ESA-treated patients is recommended every _ months.

Every 3 months.

What is the role of macrophages in systemic iron homeostasis?

They recycle iron from senescent RBCs back into circulation.

Ferroportin is the sole known _ exporter from cells to plasma.

Iron.

Hepcidin binding to ferroportin causes what effect on iron export?

Internalization and degradation of ferroportin, reducing iron export into plasma.

Which CKD-associated factors increase hepcidin levels?

Decreased renal clearance of hepcidin and chronic inflammation.

Red blood cells obtain most iron (20–30 mg/day) from where?

Macrophage-mediated recycling, not diet.

What daily amount of dietary iron is typically absorbed in healthy adults?

Approximately 1–2 mg/day.

Identify one medication guide requirement shared by ESAs and HIF-PHIs.

Both must be dispensed with a patient medication guide due to boxed warnings.

In patients receiving HIF-PHIs, what lab parameter guides dose titration every ≥ 4 weeks?

Hemoglobin concentration.

Give one rationale for not pursuing normal Hgb levels (13–15 g/dL) in CKD anemia therapy.

Higher targets increase cardiovascular and thrombotic risks without clear outcome benefits.

Why can ferritin be falsely elevated during infection or inflammation?

Because ferritin is an acute-phase reactant independent of iron status.

What ESA dose-rounding practice is common in outpatient dialysis centers?

Rounding doses to available vial sizes (e.g., 3,000 or 4,000 units).

What effect does chronic inflammation have on erythropoietin responsiveness?

It decreases responsiveness, often necessitating higher ESA doses.

Describe a circumstance in which RBC transfusion may be preferred over ESA therapy in CKD.

Acute, life-threatening anemia with Hgb < 7 g/dL requiring rapid correction.

True or False: ESA therapy should be initiated before ruling out iron deficiency.

False – Correct iron deficiency first to ensure ESA effectiveness.

How is elemental iron content derived from ferrous fumarate 325 mg?

≈ 33 % elemental iron ⇒ ~107 mg elemental iron.

What is one advantage of ferric citrate in CKD patients beyond iron supplementation?

It also functions as a phosphate binder when taken with meals.

For an ESA-treated patient, a rapid Hgb rise (> 2 g/dL in one month) necessitates what action?

Reduce the ESA dose (often by ~25 %) to mitigate thrombotic risk.

What hematology parameter measures the percentage of total blood volume occupied by RBCs?

Hematocrit (Hct).

Name two non-pharmacologic contributors to blood loss in dialysis patients.

Frequent laboratory phlebotomy and losses within the dialysis circuit.

What is the normal range for total iron-binding capacity (TIBC)?

220–420 µg/dL.

An elevated TIBC typically indicates iron stores.

Reduced (as in absolute iron deficiency).

When ferritin is < 100 ng/mL and Tsat < 20 %, what anemia type is almost certain?

Absolute iron-deficiency anemia.

Why might oral iron be ineffective in late-stage CKD despite adherence?

High hepcidin levels inhibit intestinal iron absorption.

What is the recommended minimum interval between IV iron doses to reassess effect on labs?

Typically at least 1–2 weeks after completing a course.

True or False: Darbepoetin alfa can be administered every 4 weeks in some CKD patients.

True – its longer half-life permits dosing every 2–4 weeks.

Give one practical reason to favor SQ over IV ESA administration in CKD-ND.

SQ route prolongs ESA absorption and avoids repeated venous access.