L22 - CKD Complications (2B)

What type of anemia is classically associated with CKD?

Normocytic, normochromic anemia.

Why does CKD cause anemia?

The kidneys produce about 90% of endogenous erythropoietin (EPO). Declining kidney function → ↓ EPO → ↓ RBC production and anemia.

What additional factors contribute to anemia in CKD?

↓ RBC lifespan, iron/nutritional deficiencies, and blood loss from laboratory testing or hemodialysis.

At what stage of CKD does the incidence of anemia begin to increase?

Stage 3 CKD.

What are common symptoms of anemia of CKD?

Shortness of breath, fatigue, and weakness.

What Hb level defines anemia in women and men?

Women: Hb <12 g/dL; Men: Hb <13 g/dL.

What is included in the initial evaluation of anemia in CKD?

CBC + red cell indices (MCV, MCHC), reticulocyte count, ferritin, and transferrin saturation (TSAT).

What additional tests should be considered if the cause of anemia remains unclear?

Vitamin B12, folate, peripheral smear, CRP, TSH, hemolysis studies, liver tests, and fecal occult blood testing as clinically indicated.

What are the main treatment approaches for anemia of CKD?

Supportive: adequate dietary iron and RBC transfusion when clinically indicated. Pharmacologic: iron therapy when criteria are met, ESA after correcting reversible causes, and HIF-PHI as an alternative in selected patients.

When should iron therapy be initiated in CKD G5 patients receiving hemodialysis (G5HD)?

Ferritin ≤500 ng/mL AND TSAT ≤30%.

When should iron therapy be initiated in CKD patients NOT receiving hemodialysis?

Ferritin <100 ng/mL AND TSAT <40%, OR ferritin 100–300 ng/mL AND TSAT <25%.

When should routine iron therapy be withheld in CKD?

Ferritin >700 ng/mL OR TSAT ≥40%, OR active infection.

What oral iron preparation is specifically emphasized for testing?

Ferrous sulfate.

How much elemental iron is in standard ferrous sulfate 325 mg?

20% elemental iron = 65 mg elemental iron per 325 mg tablet; given PO daily to TID.

What is the mechanism of action of iron therapy?

Provides elemental iron for hemoglobin synthesis and RBC production.

Which route of iron is preferred in CKD G5 patients receiving hemodialysis?

IV iron is preferred.

What route of iron can be used in non-hemodialysis CKD?

Oral or IV iron based on severity, response, tolerability, access, cost, and patient preference.

When can a patient be switched from oral to IV iron?

If oral iron is ineffective after 1–3 months or is poorly tolerated.

What decreases oral iron absorption?

Food and achlorhydria.

What are the common adverse effects of oral iron?

Constipation, nausea, and abdominal cramping.

What are important adverse effects of IV iron?

Allergic reactions, hypotension, dizziness, dyspnea, lower back pain, arthralgia, syncope, and arthritis.

What drugs can interact with oral iron and decrease its absorption?

Calcium preparations, antacids, H2 antagonists, and proton pump inhibitors (PPIs).

What is the general cumulative dose used for most IV iron replacement regimens?

Approximately 1,000 mg.

Which IV iron requires a test dose and has a boxed warning for anaphylactic-type reactions?

Iron dextran: 25 mg test dose required; 100 mg IV × 10 doses.

Which IV iron has a boxed warning for severe, prolonged hypophosphatemia?

Ferric carboxymaltose (Injectafer).

What are the major erythropoiesis-stimulating agents (ESAs)?

Epoetin alfa and darbepoetin alfa.

What is the mechanism of action of ESAs?

Stimulate erythropoiesis → ↑ reticulocytes and RBC production.

What are the major adverse effects of ESAs?

Hypertension, stroke/thromboembolic events, seizures, and pure red cell aplasia (PRCA).

What is an important contraindication to ESA therapy?

Uncontrolled blood pressure.

What routes can be used for ESAs in maintenance hemodialysis?

IV or subcutaneous.

What ESA route is preferred in other CKD patients?

Subcutaneous.

What must be done BEFORE starting an ESA?

Assess and correct reversible causes of anemia, especially iron deficiency and vitamin B12/folate deficiency.

Why should reversible causes of anemia be corrected before starting an ESA?

Correcting them may eliminate or reduce the need for ESA therapy.

What iron parameters require withholding iron even during ESA therapy?

Ferritin >700 ng/mL OR TSAT ≥40%.

When is it reasonable to initiate an ESA in CKD patients on maintenance dialysis?

Hb ≤9–10 g/dL.

When should ESA initiation be considered in most adults with CKD NOT receiving dialysis?

Hb 8.5–10 g/dL; individualize based on symptoms, comorbidities, transfusion avoidance, and ESA risks.

What is the target hemoglobin during ESA therapy?

Hb ≤11.5 g/dL; typically maintain 10–11.5 g/dL.

Why should Hb NOT be targeted above 11.5 g/dL with ESA therapy?

Higher Hb targets increase the risk of death, hypertension, vascular/cardiovascular events, and stroke (BOXED WARNING).

What general dosing principle should be followed with ESA therapy?

Use the lowest ESA dose needed to achieve treatment goals.

What should be done if Hb exceeds 11.5 g/dL during ESA therapy?

Dose reduction is generally preferred over temporarily discontinuing the ESA.

How should Hb be monitored after initiating ESA therapy?

Check Hb weekly until stable, then once monthly.

What should be done if Hb increases >1 g/dL in 2 weeks during ESA therapy?

Decrease the ESA dose.

What should be done if Hb increases <1 g/dL in 4 weeks during ESA therapy?

Increase the ESA dose.

What drug class is HIF-PHI?

Hypoxia-inducible factor-prolyl hydroxylase inhibitor; know the CLASS rather than the individual drug name.

What is the mechanism of HIF-PHIs?

Oral agents that stabilize HIF transcription factors → stimulate endogenous erythropoietin production.

Which is preferred after reversible causes are corrected: ESA or HIF-PHI?

ESA therapy is preferred over HIF-PHI therapy.

When may a HIF-PHI be considered?

When an ESA is not tolerated, response to ESA is inadequate, or parenteral ESA administration is not possible.

Can an ESA and HIF-PHI be used together?

NO. Do NOT combine an ESA and HIF-PHI.

In what CKD population are HIF-PHIs approved according to the lecture?

Dialysis patients only.

What major boxed warning is associated with HIF-PHIs?

Risk of vascular events and major adverse cardiovascular events (MACE).

A male CKD patient has Hb 10 g/dL. Does he meet the definition of anemia?

Yes. Anemia in men is Hb <13 g/dL.

A CKD patient has anemia but iron, B12, and folate status have not been evaluated. Should an ESA be started immediately?

No. First evaluate and correct reversible causes such as iron, vitamin B12, and folate deficiencies.

A G5HD patient has ferritin 400 ng/mL and TSAT 25%. Should iron be initiated?

Yes. G5HD criteria: ferritin ≤500 AND TSAT ≤30%.

A G5HD patient has ferritin 600 ng/mL and TSAT 20%. Do they meet the initiation criteria for iron?

No. G5HD requires BOTH ferritin ≤500 AND TSAT ≤30%.

A non-HD CKD patient has ferritin 80 ng/mL and TSAT 35%. Should iron be initiated?

Yes. Ferritin <100 AND TSAT <40%.

A non-HD CKD patient has ferritin 200 ng/mL and TSAT 20%. Should iron be initiated?

Yes. Ferritin 100–300 AND TSAT <25%.

A CKD patient has ferritin 750 ng/mL and TSAT 20%. Should routine iron be given?

No. Withhold routine iron when ferritin >700 ng/mL.

A CKD patient has ferritin 200 ng/mL and TSAT 42%. Should routine iron be given?

No. Withhold routine iron when TSAT ≥40%.

A CKD patient has an active infection but otherwise meets iron initiation criteria. Should routine iron be given?

No. Withhold routine iron during active infection.

A dialysis patient has Hb 9 g/dL after reversible causes of anemia have been corrected. What therapy can be considered?

ESA therapy; initiation is reasonable at Hb ≤9–10 g/dL in maintenance dialysis.

A non-dialysis CKD patient has Hb 9 g/dL after reversible causes have been corrected. What therapy can be considered?

ESA therapy may be considered because the usual initiation range is Hb 8.5–10 g/dL; individualize the decision.

A patient on ESA therapy reaches Hb 12 g/dL. What should be done?

Reduce the ESA dose because the target Hb should be ≤11.5 g/dL.