What is the role of immunoassay in diagnosing multiple myeloma in an older patient with suspected multiple myeloma, acute kidney injury (Impaired renal function), and symptoms suggestive of multiple myeloma?

Role of Immunoassay in Diagnosing Multiple Myeloma with Acute Kidney Injury

Serum protein electrophoresis (SPEP) and serum immunofixation electrophoresis (SIFE) are essential components of the diagnostic workup and must be performed in all patients with suspected multiple myeloma presenting with acute kidney injury, as these immunoassays detect the M-protein in approximately 80% of cases and establish critical baseline measurements for monitoring treatment response. 1, 2

Why Immunoassays Are Mandatory in This Clinical Context

Diagnostic Necessity

• SPEP is recommended by the International Myeloma Working Group as a fundamental component of the minimal diagnostic workup for all suspected plasma cell disorders. 2 This is non-negotiable in your patient with suspected myeloma and AKI.

• SIFE must follow SPEP to confirm the presence and type of heavy and light chain, providing definitive characterization of the monoclonal protein. 1

• The combination detects M-protein in 96-100% of myeloma cases, with immunofixation electrophoresis superior to SPEP alone (100% vs 96.19% detection rate). 3

Critical for AKI-Specific Diagnosis

• Light chain cast nephropathy is a myeloma-defining event and the most common cause of AKI in myeloma patients. 2 Accurate diagnosis requires complete protein evaluation including SPEP to distinguish this from other causes of kidney injury.

• Only light chain cast nephropathy qualifies as a myeloma-defining event among renal complications, making the distinction between this and other AKI causes treatment-critical. 2

The Complete Immunoassay Panel Required

Serum Testing (All Three Required)

• Serum protein electrophoresis (SPEP) - quantifies the M-protein spike 1

• Serum immunofixation electrophoresis (SIFE) - confirms the type of monoclonal immunoglobulin 1

• Serum free light chain (FLC) assay - provides the highest sensitivity when combined with SPEP 1, 2

Why All Three Are Necessary

• The National Comprehensive Cancer Network explicitly states that SPEP must be performed alongside serum FLC assays because these tests provide complementary, not redundant information. 2

• 20% of myeloma patients have secretory urinary proteins only, which would be missed without the complete panel. 1, 2

• Serum FLC assays alone cannot replace SPEP because SPEP provides the M-protein quantification needed for International Myeloma Working Group response criteria. 2

Specific Advantages in Renal Impairment

Superior Sensitivity with Kidney Dysfunction

• Serum FLC immunoassays are significantly more sensitive than urine testing in patients with renal dysfunction - detecting abnormal FLC in 54% of serum samples compared to only 25% by urine tests. 4

• In severe renal failure requiring dialysis, serum FLC measurement with an abnormal kappa/lambda ratio identified 100% of myeloma patients with 99% specificity when using the modified renal reference range (0.37-3.1 instead of 0.26-1.65). 5

• Renal excretion of monoclonal FLC significantly decreases at high serum concentrations combined with renal dysfunction, making urine testing unreliable in AKI. 4

Rapid Diagnostic Capability

• A rapid serum FLC test (Seralite®) can accurately diagnose all myeloma patients with AKI stage 3, returning 100% sensitivity and specificity using a κ:λ ratio range of 0.14-2.02. 6

• The serum FLC difference (dFLC) with an optimal cut-off of 399-400 mg/L distinguished between myeloma and non-myeloma AKI with 91% sensitivity and 100% specificity. 6

Prognostic and Treatment Monitoring Value

Predicting AKI Development and Recovery

• Serum FLC concentrations predict both the development of AKI and its recovery potential - AKI is rare when FLC is <50 mg/dL but increases significantly above 80-200 mg/dL. 2

• Recovery of renal function requires rapid and significant reduction of the involved serum FLC, making baseline measurements essential for monitoring treatment efficacy. 2

Baseline Establishment

• The same test method must be used for all serial studies to ensure accurate relative quantification - skipping the initial SPEP eliminates a critical monitoring parameter. 1, 2

• Once the M-protein is quantified, the identical test must be used for follow-up to track treatment response accurately. 1

Additional Urine Testing Still Required

24-Hour Urine Collection

• Despite superior serum testing, 24-hour urine collection for total protein, urine protein electrophoresis (UPEP), and urine immunofixation electrophoresis (UIFE) remains mandatory in the initial diagnostic workup. 1

• The serum FLC assay cannot replace 24-hour urine protein electrophoresis for monitoring patients with measurable urinary M-proteins. 1

• Random urine samples with analytes corrected relative to creatinine concentration cannot be recommended at this point and cannot replace 24-hour collection. 1

Important Caveat

• Urine-free light chain assay should not be performed - only serum FLC assays are validated. 1

Common Pitfalls to Avoid

• Never assume serum FLC alone is sufficient - SPEP provides essential M-protein quantification and immunofixation confirms the heavy and light chain type. 2

• Do not skip SIFE even if SPEP shows no measurable protein - immunofixation should be performed regardless of SPEP results as it detects monoclonal proteins missed by electrophoresis alone. 1

• Do not use the standard FLC ratio reference range (0.26-1.65) in patients with severe renal failure - use the modified renal reference range (0.37-3.1) to avoid false positives and maintain 99% specificity. 5

• Do not rely on urine testing alone in AKI patients - renal dysfunction significantly impairs FLC excretion, making urine tests unreliable. 4