In an adult with stage 3 chronic kidney disease (eGFR ≈ 45 mL/min/1.73 m²), type 2 diabetes mellitus (fasting glucose ≈ 170 mg/dL), mild hyponatremia (Na ≈ 135 mmol/L), hypocalcemia (serum calcium ≈ 7.8 mg/dL), iron‑deficiency anemia (Hb ≈ 9.2 g/dL, MCV ≈ 78 fL, serum iron ≈ 14 µg/dL, transferrin ≈ 182 mg/dL, % saturation ≈ 6 %), and leukopenia with left shift (WBC ≈ 3.7 ×10⁹/L, absolute lymphocytes ≈ 0.11 ×10⁹/L, metamyelocytes present), what diagnostic work‑up and management steps should be undertaken?

Diagnostic Work-Up and Management for Stage 3 CKD with Multiple Complications

Immediate Priority: Address Iron-Deficiency Anemia

This patient has absolute iron deficiency anemia (TSAT 6%, ferritin 14 µg/dL, transferrin 182 mg/dL) superimposed on CKD-related anemia, and iron repletion must be initiated immediately before considering erythropoietin therapy. 1, 2

Iron Deficiency Diagnosis Confirmed

• Absolute iron deficiency is definitively present: TSAT ≤20% (patient has 6%) AND ferritin ≤100 ng/mL (patient has 14 µg/dL) in non-dialysis CKD patients 1, 2, 3
• The microcytic anemia (MCV 77.9 fL), hypochromasia, and severely depressed iron parameters confirm this is predominantly iron-deficiency anemia rather than pure anemia of CKD 3, 4
• Iron supplementation should be initiated before considering erythropoietin-stimulating agents (ESAs) because adequate iron stores are required to support accelerated erythropoiesis stimulated by ESAs 1, 5

Iron Repletion Strategy

• For CKD stage 3 (non-dialysis), either intravenous or oral iron is acceptable 3, 4
• A 1-3 month trial of oral iron therapy is reasonable as first-line for non-dialysis CKD patients 6, 1
• If oral iron fails after 1-3 months or rapid correction is needed, switch to intravenous iron 6, 1
• Target TSAT >30% and ferritin >100 ng/mL before considering ESA therapy 6, 5

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Critical Diagnostic Work-Up Required

1. Investigate the Leukopenia with Left Shift

The presence of metamyelocytes (left shift) with leukopenia (WBC 3.7) and severe lymphopenia (0.11) is highly abnormal and demands immediate investigation for bone marrow pathology, infection, or malignancy. 7

• Obtain peripheral blood smear review by hematology to evaluate the left shift with metamyelocytes in the setting of leukopenia 7
• Hematology consultation is mandatory given the complex picture: microcytic anemia, leukopenia with left shift, and abnormal RBC morphology 1, 7
• Rule out myelodysplastic syndrome, bone marrow infiltration, or severe infection 7
• Check vitamin B12 and folate levels (not yet done) as deficiencies can cause cytopenias 6, 7

2. Evaluate Hypocalcemia

• Serum calcium 7.8 mg/dL requires immediate assessment of ionized calcium to determine if this is true hypocalcemia or artifact from hypoalbuminemia 6
• Check intact parathyroid hormone (PTH), 25-hydroxyvitamin D, phosphorus, and albumin levels 6
• CKD stage 3 commonly develops secondary hyperparathyroidism with mineral bone disease 6

3. Assess Albuminuria and CKD Etiology

• Obtain urine albumin-to-creatinine ratio (UACR) immediately as this is essential for CKD staging and management decisions 6
• Two of three specimens collected within 3-6 months should be abnormal to confirm persistent albuminuria 6
• Check for diabetic retinopathy as its absence in type 1 diabetes or presence in type 2 diabetes helps confirm diabetic kidney disease versus alternative etiologies 6

4. Rule Out Alternative Causes of Kidney Disease

The rapidly progressive nature suggested by multiple abnormalities warrants nephrology evaluation for possible non-diabetic kidney disease. 6

• Active urinary sediment (check urinalysis for RBCs, WBCs, casts) 6
• Rapidly decreasing eGFR or rapidly increasing albuminuria suggests alternative causes 6
• Immediate nephrology referral is indicated for diagnostic uncertainty and complex management issues 6

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Diabetes Management

Glycemic Control

• Fasting glucose 170 mg/dL indicates suboptimal diabetes control requiring medication adjustment 6
• Review current diabetes medications and adjust to achieve better glycemic targets 6

Cardio-Renal Protective Therapy

• Initiate SGLT2 inhibitor immediately (if eGFR ≥20 mL/min/1.73 m²) to reduce CKD progression and cardiovascular events 6
• Consider GLP-1 receptor agonist with demonstrated benefit in diabetic kidney disease for cardiovascular risk reduction 6
• These agents provide benefit independent of glycemic control and should be prioritized 6

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Nephrology Referral Criteria Met

This patient meets multiple criteria for immediate nephrology referral: 6

1. Diagnostic uncertainty: Leukopenia with left shift, severe iron deficiency, and multiple cytopenias suggest non-diabetic causes 6
2. Difficult management issues: Multiple competing priorities requiring subspecialty coordination 6
3. Stage 3b CKD (eGFR 45.86): Approaching the threshold for mandatory referral at eGFR <30 mL/min/1.73 m² 6

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Monitoring Plan

Short-Term (7-14 Days)

• Recheck serum creatinine and potassium after any medication changes, particularly if ACE inhibitors, ARBs, or diuretics are initiated or adjusted 6
• Repeat ionized calcium if initial value confirms true hypocalcemia 6

Medium-Term (1-3 Months)

• Reassess iron parameters (TSAT, ferritin) and hemoglobin after iron supplementation trial 6, 1
• Acceptable response is hemoglobin increase ≥2 g/dL within 4 weeks of iron therapy 1
• If iron repletion alone is insufficient after 1-3 months, ESA therapy may be indicated 1, 5

Ongoing

• Monitor UACR and eGFR at least twice yearly for stage 3 CKD 6
• Aim to reduce urinary albumin by ≥30% if albuminuria ≥300 mg/g to slow CKD progression 6

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Common Pitfalls to Avoid

• Do not start ESA therapy before correcting iron deficiency as this leads to poor response and increased ESA requirements 1, 5
• Do not dismiss the leukopenia with left shift as this may represent serious underlying pathology requiring urgent evaluation 7
• Do not rely on serum creatinine alone to assess kidney function; always use eGFR and UACR 6
• Do not delay nephrology referral in the presence of diagnostic uncertainty or complex management issues 6