What is the difference between Urine Protein Electrophoresis (UPEP) and Serum Protein Electrophoresis (SPEP)?

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Last updated: August 26, 2025View editorial policy

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Difference Between UPEP and SPEP

Serum Protein Electrophoresis (SPEP) analyzes proteins in blood serum, while Urine Protein Electrophoresis (UPEP) examines proteins in urine, with both tests being complementary rather than interchangeable in the evaluation of plasma cell disorders. 1

Key Differences

Sample Source

  • SPEP: Uses blood serum collected in a serum-separator tube or red-top tube
  • UPEP: Uses a 24-hour urine collection sample

Proteins Detected

  • SPEP: Detects serum proteins including albumin, alpha-1, alpha-2, beta, and gamma globulins
  • UPEP: Specifically identifies proteins excreted in urine, including Bence-Jones proteins (free light chains)

Clinical Utility

  • SPEP:

    • Primary screening test for monoclonal gammopathies
    • Sensitivity of approximately 71% for detecting plasma cell disorders 2
    • Can detect serum M-proteins but may miss light chain disease
    • Provides information about overall protein distribution patterns
  • UPEP:

    • Essential for detecting Bence-Jones proteinuria
    • Critical for monitoring patients with light chain disease
    • Provides distinctive patterns that can indicate the source of proteinuria 3
    • Cannot be replaced by serum free light chain assay for monitoring patients with measurable urinary M-proteins 1

Clinical Applications

Multiple Myeloma Diagnosis

  • According to NCCN guidelines, both tests are recommended as part of the initial diagnostic workup for suspected plasma cell disorders 1
  • In a Mayo Clinic review of 1,027 newly diagnosed multiple myeloma patients:
    • 20% had secretory urinary proteins (detectable by UPEP)
    • 3% had neither serum nor urine proteins (nonsecretory myeloma) 1

Complementary Nature

  • UPEP and SPEP supplement each other in characterizing proteinuria 3
  • UPEP can provide distinctive patterns indicating the source of proteinuria in renal diseases independent of gammopathies
  • Combined use of UPEP and SPEP with their respective immunofixation tests (UIFE and SIFE) provides the most comprehensive evaluation

Testing Protocol

  • For complete evaluation of plasma cell disorders, the following tests should be ordered together:
    • SPEP with serum immunofixation electrophoresis (SIFE)
    • UPEP with urine immunofixation electrophoresis (UIFE)
    • Serum free light chain (FLC) assay 4

Important Considerations

Monitoring Disease

  • Once an M-protein is quantified, the same test must be used for serial studies to ensure accurate relative quantification 1
  • UPEP remains essential for monitoring patients with measurable urinary M-proteins, as the serum FLC assay cannot replace it 1

Common Pitfalls

  • Failing to perform urine studies can lead to missed diagnoses
  • Relying solely on SPEP without UPEP may miss light chain disease
  • Not using consistent testing methods for serial monitoring can lead to inaccurate assessment of disease progression or response to treatment

By understanding the differences and complementary nature of SPEP and UPEP, clinicians can appropriately utilize these tests to diagnose and monitor plasma cell disorders effectively.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Serum Protein Electrophoresis (SPEP) Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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