What are the differential diagnoses for a 64-year-old male with a history of Chronic Kidney Disease (CKD) stage V, Hypertension, and Diabetes Mellitus, presenting with weakness, dizziness, and anemia?

Differential Diagnoses for Weakness and Anemia in CKD Stage V

The primary differential diagnosis in this 64-year-old male with CKD stage V, diabetes, hypertension, and recurrent anemia with weakness is anemia of chronic kidney disease due to erythropoietin deficiency, complicated by iron deficiency (likely from chronic gastrointestinal blood loss given his medication profile). 1

Primary Diagnosis

Anemia of Chronic Kidney Disease (CKD-Related Anemia)

• Most likely diagnosis given CKD stage V with insufficient endogenous erythropoietin production 1
• Typically presents as normocytic, normochromic anemia 1
• Expected in patients with eGFR <30 mL/min/1.73 m² 1
• Associated with weakness, dizziness, and pale appearance as described 1
• Prevalence increases dramatically as kidney function declines, affecting majority of stage 5 CKD patients 1, 2

Contributing/Complicating Factors

Iron Deficiency Anemia

• Critical to evaluate given multiple risk factors in this patient 1
• Patient on aspirin (61% of CKD patients with anemia), NSAIDs (73%), and potentially antiplatelet agents - all increase GI bleeding risk 2
• Absolute iron deficiency: depleted iron stores (ferritin <100 μg/mL) 1
• Functional iron deficiency: adequate stores but insufficient availability for erythropoiesis (TSAT <20%) 1
• 80.5% of CKD patients with normocytic anemia and Hb ≤11 g/dL have low ferritin 2
• 20-25% of severe anemia cases in CKD are microcytic, suggesting iron deficiency 2

Diabetic Kidney Disease-Specific Anemia

• Develops earlier and more severely than non-diabetic CKD 3, 4
• Mechanisms include: autonomic neuropathy affecting oxygen sensing, urinary EPO loss, inflammatory cytokines, and poor EPO response 3
• Diabetes patients have higher prevalence of anemia at all CKD stages compared to non-diabetics 1, 3

Gastrointestinal Blood Loss

• High suspicion given medication profile: aspirin, likely NSAIDs for any pain, possible anticoagulation for ASCVD/CAD 2
• 53.1% of CKD patients with anemia are on both aspirin and NSAIDs 2
• Uremic platelet dysfunction in stage 5 CKD increases bleeding tendency 3
• Should prompt evaluation for occult GI bleeding 1

Secondary Differential Diagnoses

Folate or Vitamin B12 Deficiency

• Consider if macrocytic indices present (MCV >100 fL) 1
• Less common but should be evaluated in initial workup 1
• Can coexist with CKD-related anemia 1

Inflammation/Chronic Disease

• Inflammatory cytokines inhibit erythropoiesis and increase hepcidin 5
• Common in CKD patients with cardiovascular comorbidities 1, 5
• Contributes to functional iron deficiency 5

Malnutrition

• Suggested by eating "only four spoonfuls of food" 1
• Protein-energy wasting common in advanced CKD 1
• Can worsen anemia through multiple mechanisms 1

Hyperparathyroidism (Secondary)

• Severe hyperparathyroidism can contribute to anemia in CKD 1
• Bone marrow fibrosis from prolonged hyperparathyroidism 1
• Expected in stage 5 CKD 1

Uremic Toxins

• Shortened red blood cell survival in uremia 1
• Direct bone marrow suppression 1
• Significant in stage 5 CKD 1

Less Likely but Important to Exclude

Hypothyroidism

• Can contribute to anemia 1
• Common comorbidity in CKD patients 1

Hemoglobinopathies

• Less likely given age of presentation 1
• Would have manifested earlier in life 1

Aluminum Toxicity

• Rare in modern dialysis practice 1
• Historical concern in CKD patients 1

Hematologic Malignancy

• Consider if pancytopenia or abnormal white cell/platelet counts 1
• Requires complete blood count evaluation 1

Critical Diagnostic Workup Required

Initial Laboratory Evaluation 1

• Complete blood count with red cell indices, white blood cell differential, platelet count
• Absolute reticulocyte count
• Serum ferritin level
• Transferrin saturation (TSAT)
• Serum vitamin B12 and folate levels
• Comprehensive metabolic panel including creatinine for eGFR calculation

Additional Testing Based on Findings 1

• Stool guaiac or fecal immunochemical test for occult blood
• Thyroid function tests
• Parathyroid hormone level
• Peripheral blood smear if abnormal indices

Clinical Pitfalls to Avoid

• Do not assume all anemia in CKD is solely EPO deficiency - iron deficiency is present in >60% of normocytic anemia cases 2
• Medication review is mandatory before considering erythropoietin therapy - 53% are on aspirin plus NSAIDs 2
• Oral iron often fails in CKD patients - 56.3% prescribed oral iron remain anemic 2
• Pruritus mentioned in history may indicate uremia, suggesting need for dialysis consideration 1
• Cardiovascular disease is more common than kidney failure as cause of death in CKD patients with anemia 1