What abnormality is seen in Urine Protein Electrophoresis (UPEP) to diagnose multiple myeloma?

Monoclonal Protein Abnormalities in Urine Protein Electrophoresis (UPEP) for Multiple Myeloma Diagnosis

The key abnormality seen in Urine Protein Electrophoresis (UPEP) to diagnose multiple myeloma is the presence of monoclonal protein (M-protein), specifically Bence Jones proteins which are free light chains excreted in the urine.

Urine Protein Analysis in Multiple Myeloma Diagnosis

Primary Abnormalities Detected in UPEP

• UPEP detects the presence of monoclonal proteins (M-proteins) in the urine, which are a hallmark of multiple myeloma 1
• The monoclonal proteins appear as a sharp, discrete band or spike on the electrophoresis pattern, representing the abnormal immunoglobulin light chains 1
• These urinary light chains are known as Bence Jones proteins, which are either kappa or lambda free light chains that have passed through the glomerular filtration barrier 1

Quantification and Characterization

• 24-hour urine collection is recommended for total protein quantification and UPEP analysis 1
• Urine immunofixation electrophoresis (UIFE) is typically performed alongside UPEP to specifically identify the type of monoclonal protein present 1
• The kappa/lambda ratio in urine is significantly abnormal in multiple myeloma (>5 or <0.75), which helps in diagnosis 2, 3

Clinical Significance of Urinary M-Proteins

Prevalence and Diagnostic Value

• Approximately 20% of newly diagnosed multiple myeloma patients have secretory urinary proteins detectable by UPEP 1
• The presence of urinary M-protein >200 mg/24h is considered clinically significant and can be one of the multiple myeloma defining events 2, 4
• Some patients may have light chain multiple myeloma, where the abnormal plasma cells produce only light chains rather than complete immunoglobulins 5, 2

Monitoring Disease

• UPEP is essential for monitoring disease progression and response to treatment in patients with measurable urinary M-proteins 1
• The serum free light chain (FLC) assay cannot completely replace 24-hour UPEP for monitoring patients with measurable urinary M-proteins 1, 2
• For accurate monitoring, it's crucial to use the same test for serial measurements to ensure accurate relative quantification 1

Response Assessment Using UPEP

Response Criteria

• Complete Response (CR): Negative immunofixation on both serum and urine 5, 2
• Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis, or ≥90% reduction in serum M-protein plus urine M-protein <100 mg/24h 5, 2
• Partial Response (PR): Reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24h 5, 2

Important Considerations and Pitfalls

Limitations and Caveats

• Some patients (approximately 3%) may have nonsecretory myeloma with neither serum nor urine detectable proteins 1
• Renal function can affect the excretion of light chains, potentially leading to false interpretations 2, 1
• For light chain multiple myeloma, both serum FLC assay and UPEP should be used for comprehensive assessment 5, 2
• The involved light chain in urine is significantly elevated in light chain multiple myeloma, while serum light chains may be within normal range 3, 2

Practical Implementation

• After quantifying the M-protein, it's essential to use the same test for serial studies to ensure accurate relative quantification 1
• Response assessments should be confirmed with a second measurement for accuracy 5, 2