Immunofixation Electrophoresis, Not Fluoroscopy, Supplements SPEP
Immunofixation electrophoresis (IFE) of serum and urine—not fluoroscopy—is the essential supplementary test to serum protein electrophoresis (SPEP) when evaluating suspected multiple myeloma with acute kidney injury. 1, 2
The Correct Diagnostic Approach
Primary Laboratory Testing Sequence
SPEP serves as the initial quantitative screening test that is inexpensive and easy to perform, but has limited sensitivity (71%) for detecting plasma cell neoplasms 1, 3
Serum immunofixation electrophoresis (SIFE) must follow SPEP because it is significantly more sensitive than SPEP alone for identifying and typing monoclonal immunoglobulins 1, 2
24-hour urine collection with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) is mandatory, as 80% of myeloma patients with AKI have Bence Jones proteinuria that may not be detected by serum testing alone 1, 2, 4
Serum free light chain assay (SFLCA) is critical for measuring κ and λ free light chains independently and determining the κ:λ ratio, with abnormal ratios indicating clonality (normal ratio 0.26-1.65, or 0.34-3.10 in severe renal impairment) 1, 2
Why Fluoroscopy Is Not Relevant
Fluoroscopy is a continuous X-ray imaging technique used for real-time visualization of anatomical structures and has no role in detecting or quantifying monoclonal proteins 1
The ACR Appropriateness Criteria for renal failure do not recommend fluoroscopy for evaluating AKI, instead focusing on ultrasound, CT, and MRI for structural kidney assessment 1
Skeletal survey using plain radiographs—not fluoroscopy—is appropriate for detecting lytic bone lesions in multiple myeloma, but this evaluates bone involvement rather than supplementing SPEP 3
Complete Diagnostic Algorithm for Myeloma with AKI
Initial Laboratory Panel
- Serum creatinine, electrolytes, and eGFR calculation using MDRD equation 1, 5
- SPEP as the initial screening test 1, 2
- SIFE for definitive identification and typing of monoclonal protein 1, 2
- 24-hour urine collection with UPEP and UIFE 1, 2
- Serum free light chain assay with κ:λ ratio 1, 2
- Quantitative immunoglobulins 2
When to Proceed to Kidney Biopsy
Biopsy is advised when: AKI stage 3, eGFR <60 ml/min/1.73m² with >2 ml/min/1.73m² per year decline, proteinuria with hematuria, albumin:creatinine ratio >30 mg/mmol, or Fanconi syndrome 1
Biopsy distinguishes light chain cast nephropathy (most common) from light chain deposition disease and AL amyloidosis, which require different management approaches 1, 6
Critical Interpretation Points
SPEP has high negative predictive value (94%) but poor positive predictive value (47%), meaning a negative SPEP does not rule out myeloma, especially in patients with light chain-only disease 3
Free light chain levels >150 mg/dL with urine M-spike >200 mg/day and albuminuria <10% strongly suggest light chain cast nephropathy even before biopsy confirmation 2
Serum FLC concentrations >50 mg/dL significantly increase AKI risk, with dramatic increases when exceeding 80-200 mg/dL 5, 7
Common Pitfalls to Avoid
Never rely on SPEP alone—approximately 29% of myeloma cases with AKI will be missed without immunofixation and free light chain assays 3
Do not delay treatment waiting for complete diagnostic workup if light chain cast nephropathy is strongly suspected based on clinical presentation and initial labs 1, 2
Remember that renal impairment alters free light chain clearance, requiring adjusted interpretation of κ:λ ratios in patients with eGFR <60 ml/min/1.73m² 1, 2
Avoid nephrotoxic medications (NSAIDs, IV contrast) during evaluation, as these precipitate AKI in 15-31% of cases 1, 4