Bence Jones proteinuria
Summary
Bence Jones proteins are free monoclonal immunoglobulin light chains (kappa or lambda) found in the urine, classically associated with multiple myeloma and other plasma cell dyscrasias. They are not detected by standard urine dipstick (which detects albumin) and require urine protein electrophoresis (UPEP) or immunofixation for detection.
Detail
Bence Jones proteinuria occurs when malignant plasma cells overproduce monoclonal light chains that are small enough to be filtered by the glomerulus and excreted in urine. This is most classically seen in multiple myeloma, but also occurs in Waldenström macroglobulinemia, AL (primary) amyloidosis, and monoclonal gammopathy of undetermined significance (MGUS).
Pathophysiology: Light chains are freely filtered due to their small size (~22-24 kDa) and can overwhelm the proximal tubule's reabsorptive capacity. Excess light chains precipitate with Tamm-Horsfall protein in the distal tubule, forming casts that cause 'myeloma cast nephropathy' (light chain cast nephropathy), a major cause of renal failure in multiple myeloma. Light chains are also directly nephrotoxic to proximal tubular cells, contributing to Fanconi syndrome (type 2 RTA) in some cases.
Clinical significance: Bence Jones proteins are NOT detected by urine dipstick, which uses a colorimetric reaction specific for albumin. This creates a classic USMLE teaching point: a patient with significant proteinuria on 24-hour urine collection but a negative or trace urine dipstick should raise suspicion for light chain proteinuria. Diagnosis requires urine protein electrophoresis (UPEP) with immunofixation, which will show a monoclonal spike, or serum free light chain assay (now often preferred due to higher sensitivity).
Associated findings in multiple myeloma include: CRAB criteria (hyperCalcemia, Renal insufficiency, Anemia, Bone lesions/lytic lesions on imaging), serum protein electrophoresis showing M-spike, rouleaux formation on peripheral smear, and increased susceptibility to infections due to functional hypogammaglobulinemia.
Histologically, light chain cast nephropathy shows fractured, glassy-appearing casts in the distal tubules with a multinucleated giant cell reaction. AL amyloidosis results from light chain deposition that forms beta-pleated sheets, staining Congo red positive with apple-green birefringence under polarized light.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- UpToDate: Multiple Myeloma
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