In multiple myeloma (MM), a plasma cell malignancy, there is often a discrepancy between the amount of protein detected in urine by standard methods (e.g., urinary dipstick) and the actual protein levels present, particularly due to the production of monoclonal light chains (Bence Jones proteins). Below, I’ll explain the discrepancy, how it relates to MM, and how to interpret urinary dipstick results, including calculations for estimating proteinuria.

1. Urinary Protein Discrepancy in Multiple Myeloma
   What is the discrepancy?
   Urinary dipstick primarily detects albumin: The dipstick test is designed to detect albumin, the most common protein in urine in conditions like nephrotic syndrome or glomerular disease. It is less sensitive to other proteins, such as light chains (Bence Jones proteins) produced in MM.

Bence Jones proteins in MM: In MM, malignant plasma cells produce excessive monoclonal immunoglobulin light chains (kappa or lambda), which are filtered by the glomeruli and excreted in urine. These proteins are not effectively detected by dipstick, leading to an underestimation of total proteinuria.

Clinical implication: A patient with MM may have significant proteinuria (due to light chains) but a negative or weakly positive dipstick result. This discrepancy suggests the need for more specific tests to detect Bence Jones proteins.

Why does this happen?
Dipstick tests use a colorimetric reaction (e.g., tetrabromophenol blue) that is highly specific for albumin’s negative charge. Light chains have different physicochemical properties and do not trigger the same reaction.

Total urinary protein, including light chains, is better quantified by methods like 24-hour urine collection or urine protein electrophoresis (UPEP).

2. Multiple Myeloma and Proteinuria
   Role of proteinuria in MM:
   Bence Jones proteinuria: Light chains are nephrotoxic and can cause renal damage, including light chain cast nephropathy (myeloma kidney), proximal tubular dysfunction, or amyloidosis.

Diagnostic importance: Detection of Bence Jones proteins in urine is a hallmark of MM and is part of the diagnostic workup, alongside serum protein electrophoresis (SPEP), serum free light chain assays, and bone marrow biopsy.

Quantification: UPEP and immunofixation electrophoresis are used to confirm and quantify light chains, as dipsticks are unreliable.

When to suspect MM:
Persistent proteinuria with a negative or weakly positive dipstick.

Systemic symptoms like bone pain, fatigue, anemia, hypercalcemia, or renal impairment (CRAB criteria: Calcium elevation, Renal failure, Anemia, Bone lesions).

Unexplained renal dysfunction, especially with low albuminuria but high total protein.

3. Urinary Dipstick: How to Calculate and Interpret
   How the dipstick works:
   The dipstick’s protein pad changes color based on the concentration of albumin in urine. Results are reported semi-quantitatively (e.g., negative, trace, 1+, 2+, 3+, 4+).

Approximate correlations:
Negative: <15 mg/dL

Trace: 15–30 mg/dL

1+: 30–100 mg/dL

2+: 100–300 mg/dL

3+: 300–1000 mg/dL

4+: >1000 mg/dL

These values reflect albumin concentration, not total protein or light chains.

Limitations in MM:
A negative or trace dipstick result does not rule out significant proteinuria in MM, as Bence Jones proteins are missed.

False positives can occur with highly concentrated urine, hematuria, or urinary tract infections.

Calculating proteinuria:
To estimate total proteinuria accurately, dipstick results are insufficient. Instead, use:
Spot urine protein-to-creatinine ratio (UPCR):
Collect a random urine sample.

Measure urine protein (mg/dL) and creatinine (mg/dL).

Calculate UPCR = Urine protein (mg/dL) ÷ Urine creatinine (mg/dL).

Interpretation (approximate):
Normal: <0.2 mg/mg

Nephrotic range: >3.5 mg/mg

In MM, UPCR may be elevated due to light chains, but dipstick may underestimate.

24-hour urine collection:
Gold standard for quantifying total proteinuria.

Normal: <150 mg/24 hours.

In MM, proteinuria >500 mg/24 hours (often >1 g/24 hours) is common, primarily due to light chains.

Requires UPEP to confirm Bence Jones proteins.

Steps to interpret dipstick in suspected MM:
Perform dipstick test:
If negative/trace but clinical suspicion for MM is high (e.g., renal failure, bone pain), proceed to advanced testing.

If positive (e.g., 1+ or higher), consider other causes of albuminuria (e.g., diabetes, glomerulonephritis) but still evaluate for MM if indicated.

Order confirmatory tests:
UPEP and immunofixation: Detects and characterizes Bence Jones proteins.

Serum free light chain assay: Measures kappa/lambda ratio (abnormal if <0.26 or >1.65).

24-hour urine protein: Quantifies total proteinuria.

Correlate with clinical findings:
Renal impairment without significant albuminuria suggests light chain nephropathy.

Systemic MM features (CRAB criteria) warrant hematology referral.

4. Practical Approach to Suspected MM with Dipstick Discrepancy
   Initial evaluation:
   If dipstick is negative/trace but proteinuria is suspected, do not rely on dipstick alone.

Order UPCR or 24-hour urine collection to quantify total protein.

Confirm Bence Jones proteins:
UPEP and immunofixation are essential to detect light chains.

Further workup:
SPEP and serum free light chain assay to evaluate for monoclonal gammopathy.

Imaging (e.g., skeletal survey) for lytic lesions.

Bone marrow biopsy if MM is strongly suspected.

Management:
Treat underlying MM (e.g., chemotherapy, autologous stem cell transplant).

Manage renal complications (e.g., hydration, avoid nephrotoxic drugs).

Monitor proteinuria and renal function regularly.

5. Key Takeaways
   Dipstick is unreliable in MM: It underestimates proteinuria due to poor sensitivity for Bence Jones proteins.

Discrepancy is a clue: Low dipstick protein with high total proteinuria (via UPCR or 24-hour collection) suggests light chain proteinuria.

Use specific tests: UPEP, immunofixation, and serum free light chain assays are critical for diagnosis.

Quantify proteinuria accurately: 24-hour urine or UPCR provides a better estimate than dipstick.

Suspect MM in context: Unexplained renal failure, bone pain, or CRAB criteria should prompt further evaluation.