When should Myeloma kidney be suspected?

When to Suspect Myeloma Kidney

Myeloma kidney (light chain cast nephropathy) should be suspected in any patient with acute kidney injury who has elevated serum creatinine (≥2 mg/dL) or reduced eGFR (<40 mL/min/1.73 m²), especially when accompanied by proteinuria that consists mainly of light chains rather than albumin. 1

Clinical Scenarios That Should Trigger Suspicion

Laboratory Findings

• Serum creatinine ≥2 mg/dL or eGFR <40 mL/min/1.73 m² 1
• Proteinuria with predominance of light chains rather than albumin 1
• Elevated serum free light chain (FLC) levels, particularly when >50-80 mg/dL 1
• Abnormal serum free light chain ratio (kappa/lambda) 1
• Presence of monoclonal protein on serum protein electrophoresis 1

Associated Clinical Features

• Presence of other CRAB features of multiple myeloma:
  • Calcium elevation (≥11.5 mg/dL) 1
  • Renal failure (as described above)
  • Anemia (hemoglobin <10 g/dL or >2 g/dL below lower limit of normal) 1
  • Bone lesions (lytic lesions, severe osteopenia, or pathologic fractures) 1

High-Risk Scenarios

• Rapid worsening of kidney function without other obvious causes 1
• Unexplained acute kidney injury in patients >40 years of age 1
• Concurrent dehydration, hypercalcemia, or use of nephrotoxic medications in a patient with monoclonal gammopathy 1

Diagnostic Approach

Initial Workup

1. Serum creatinine and eGFR calculation (using MDRD or CKD-EPI formula) 1
2. Complete blood count to assess for anemia 1
3. Serum calcium level 1
4. Serum protein electrophoresis and immunofixation 1
5. Serum free light chain assay 1
6. 24-hour urine collection for:
   • Total protein quantification
   • Urine protein electrophoresis
   • Urine immunofixation 1

When to Perform Renal Biopsy

• If proteinuria consists mainly of light chains with high serum levels of free light chains, a renal biopsy may not be necessary 1
• Consider biopsy when:
  • Other conditions (diabetes, chronic hypertension) are present that could explain renal dysfunction 1
  • The cause of renal insufficiency is not clearly attributable to myeloma 1
  • Suspicion of other pathologies like amyloidosis or monoclonal immunoglobulin deposition disease 1

Pathophysiological Mechanism

Light chain cast nephropathy occurs when:

1. Excessive monoclonal free light chains are produced by myeloma cells
2. These light chains interact with Tamm-Horsfall protein in the loop of Henle
3. This interaction forms casts that obstruct the tubules 1
4. Tubular obstruction leads to rupture and immune response
5. Additional injury occurs through:
   • Hydrogen peroxide production by the free light chains
   • Activation of inflammatory pathways (NF-κB, ASK1, JAK-STAT) 1

Clinical Significance

Early recognition of myeloma kidney is critical because:

• Renal impairment in multiple myeloma has the greatest negative impact on overall survival among all CRAB features 1
• Recovery of kidney function can reverse this negative impact on survival 1
• Early and significant reduction of serum free light chains is essential for renal recovery 1
• Patients with myeloma kidney should be considered a medical emergency 1

Common Pitfalls to Avoid

1. Failing to consider multiple myeloma in older patients with unexplained acute kidney injury
2. Attributing proteinuria to other causes without checking for light chains
3. Relying only on serum creatinine rather than also measuring free light chains
4. Delaying appropriate anti-myeloma therapy, which should be initiated promptly
5. Missing other potential causes of renal dysfunction in myeloma patients (hypercalcemia, dehydration, nephrotoxic medications) 1

Remember that myeloma kidney is present in 20-50% of patients with multiple myeloma and represents approximately 80-90% of severe acute kidney injury cases in these patients 2. Early recognition and intervention are crucial for improving outcomes.