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ESA Hyporesponsiveness GI Investigation Priority — ESENeph MCQ

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ModerateChronic Kidney DiseaseESA Hyporesponsiveness GI Investigation PriorityESENeph

A 55-year-old woman with CKD G3b (eGFR 32 mL/min/1.73m2) presents with symptomatic anaemia (Hb 85 g/L). She has had an inadequate response to darbepoetin alfa despite dose escalation over 3 months (current dose 150 mcg fortnightly). Iron studies are replete (ferritin 450 ug/L, TSAT 28%). CRP is 45 mg/L. What is the MOST important next investigation?

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Correct answer: E — Investigation for occult blood loss (upper and lower GI endoscopy)

ESA hyporesponsiveness (inadequate Hb rise despite adequate ESA dosing with replete iron) has a broad differential. The most common cause is occult blood loss (GI malignancy, angiodysplasia, peptic ulceration) — CKD patients on haemodialysis lose an estimated 1-2 g iron per year through dialysis circuits, blood sampling, and GI losses. With iron replete and elevated CRP, the differential also includes chronic infection, inflammation, malignancy, and secondary hyperparathyroidism. However, GI investigation should be the priority as it identifies the most common treatable and potentially life-threatening cause. PRCA (anti-EPO antibodies) is very rare and presents with sudden complete loss of erythropoiesis.

Reference: KDIGO 2025 – Anaemia in CKD; UKKA 2025 – Anaemia Guideline; Kilpatrick et al 2008 – ESA Hyporesponsiveness