What is meant by secretory urinary protein only in an older patient with suspected multiple myeloma and impaired renal function?

Secretory Urinary Protein Only in Multiple Myeloma

"Secretory urinary protein only" refers to a subset of multiple myeloma patients (approximately 3% of cases) who produce monoclonal free light chains (Bence Jones proteins) that are detectable exclusively in the urine, with no measurable monoclonal protein (M-protein) spike visible on serum protein electrophoresis. 1

Clinical Definition and Characteristics

• This pattern represents light chain-only multiple myeloma where malignant plasma cells secrete monoclonal immunoglobulin light chains (κ or λ) without producing intact immunoglobulin heavy chains 1

• These patients excrete Bence Jones proteins in urine that can be quantified through 24-hour urine collection with urine protein electrophoresis (UPEP) and urine immunofixation electrophoresis (UIFE) 1

• The median excretion of Bence Jones protein in these patients ranges from 0.06 to 2.45 g/24h, though this varies considerably 2

Critical Diagnostic Implications for Older Patients with Renal Impairment

• In patients with impaired renal function, the absence of serum M-protein does NOT rule out multiple myeloma, as light chains may be rapidly filtered and excreted by the kidneys or catabolized, making them undetectable in serum by standard electrophoresis 1

• Renal insufficiency (creatinine ≥2 mg/dL) is one of the defining CRAB criteria for symptomatic multiple myeloma and is frequently caused by light chain cast nephropathy from Bence Jones proteins 1

• The serum free light chain (FLC) assay demonstrates 100% sensitivity for detecting these cases and should always be performed, as it can identify monoclonal light chains even when serum protein electrophoresis is negative 1, 2

Essential Diagnostic Workup

When "secretory urinary protein only" is suspected, the following tests are mandatory:

• 24-hour urine collection for total protein, UPEP, and UIFE—this cannot be replaced by random urine samples 1

• Serum free light chain assay with κ/λ ratio—this achieves maximum sensitivity and will be abnormal in 100% of light chain myeloma cases 1, 3, 2

• Serum protein electrophoresis (SPEP) and serum immunofixation (SIFE)—these may be negative or show only faint bands in light chain-only disease 1

• Bone marrow biopsy—required to document ≥10% clonal plasma cells for diagnosis of symptomatic myeloma 1

Important Clinical Pitfalls

• Do not rely solely on serum protein electrophoresis in older patients with renal dysfunction, as 15-20% of myeloma cases produce only light chains that may not create a visible M-spike on standard SPEP 1, 3

• In Bence Jones myeloma, 86% of cases show detectable paraproteinemia in serum by immunofixation, with λ-type having higher detection rates (95.7%) compared to κ-type (77.8%) 2

• Patients with light chain-only disease demonstrate biochemical signs of secondary immunodeficiency with suppressed uninvolved immunoglobulins (IgG, IgA, IgM) and elevated β2-microglobulin 2

Prognostic Considerations

• Light chain smoldering multiple myeloma (defined as ≥0.5 g/24h urinary light chain excretion or ≥10% bone marrow plasma cells without end-organ damage) carries a 27.8% risk of progression to active myeloma at 5 years and 56.5% at 15 years 4

• Risk factors for progression include: amount of urinary M-protein excretion, bone marrow plasma cell percentage, markedly abnormal FLC ratio (<0.01 or >100), and reduction of all three uninvolved immunoglobulins 4