Renal Dysfunction in Multiple Myeloma: Light Chain Cast Nephropathy
The most likely cause of this patient's deteriorating kidney function is C: Accumulation of monoclonal light chains (light chain cast nephropathy). This patient presents with the classic triad of multiple myeloma: persistent back pain (suggesting lytic bone lesions), elevated creatinine, and 20% plasma cells on bone marrow biopsy, making light chain cast nephropathy the primary mechanism of renal injury 1.
Diagnostic Reasoning
Why Light Chain Cast Nephropathy is Most Likely
Bone marrow findings confirm plasma cell dyscrasia: The presence of 20% plasma cells definitively establishes a clonal plasma cell disorder, which produces nephrotoxic monoclonal immunoglobulin or light chains 1.
Renal insufficiency in myeloma is predominantly due to light chain cast nephropathy: In patients with myeloma, elevated serum creatinine with eGFR <60 mL/min/1.73 m² is usually caused by light chain cast nephropathy, where free light chains are filtered by glomeruli and precipitate in distal tubules, causing tubular obstruction and interstitial inflammation 1.
Clinical presentation matches myeloma kidney: The combination of back pain (bone involvement), elevated creatinine, and confirmed plasma cell proliferation creates the pathophysiologic environment for light chain-mediated kidney injury 1.
Why Other Options Are Less Likely
A. Acute Tubular Necrosis (ATN):
- While NSAIDs can cause ATN through hemodynamic effects and vasoconstriction, this typically occurs in volume-depleted states or patients with pre-existing risk factors 2, 3.
- ATN from NSAIDs would not explain the bone marrow findings of 20% plasma cells 2.
- The clinical scenario points to a chronic process (3 months of symptoms) rather than acute tubular injury 1.
B. Kidney Stones:
- Hypercalcemia in myeloma can theoretically cause nephrolithiasis, but stones would not be the primary mechanism of renal dysfunction in this context 1.
- The bone marrow findings and clinical presentation are inconsistent with simple obstructive uropathy 1.
D. Waldenström Macroglobulinemia:
- This condition involves lymphoplasmacytic lymphoma producing IgM monoclonal protein, not the plasma cell proliferation seen here 1, 4.
- Waldenström's typically presents with hyperviscosity symptoms rather than lytic bone lesions and back pain 1.
- The bone marrow in Waldenström's shows lymphoplasmacytic infiltration, not the 20% plasma cells described 4.
Pathophysiology of Light Chain Cast Nephropathy
Mechanism of injury: Monoclonal free light chains (kappa or lambda) are filtered through glomeruli and overwhelm tubular reabsorption capacity, precipitating in distal tubules with Tamm-Horsfall protein to form obstructing casts 1.
Contributing factors beyond light chains: Hypercalcemia, volume depletion, and hyperuricemia frequently coexist and exacerbate renal injury, but the fundamental problem is light chain production 1.
Distinction from other myeloma-related kidney diseases: When proteinuria consists predominantly of light chains with high serum free light chain levels, cast nephropathy is the likely diagnosis; however, concomitant amyloidosis or monoclonal immunoglobulin deposition disease should be suspected when albuminuria is present without proportionally high light chain levels 1.
Diagnostic Workup Required
Confirm light chain production: Serum protein electrophoresis, serum immunofixation, 24-hour urine protein electrophoresis, and serum free light chain assay are essential to quantify and characterize the monoclonal protein 1.
When renal biopsy is indicated: If proteinuria is not predominantly light chains, or if there is no clear explanation for renal insufficiency, kidney biopsy should be performed to assess for alternative pathophysiology such as monoclonal immunoglobulin deposition disease or membranoproliferative glomerulonephritis 1.
When biopsy may be unnecessary: If proteinuria consists predominantly of light chains with high serum free light chain levels and the clinical picture clearly points to myeloma, biopsy may not be necessary 1.
Critical Management Principles
Immediate myeloma therapy is essential: Bortezomib-containing regimens should be initiated as soon as possible to decrease production of nephrotoxic clonal immunoglobulin 1.
Bortezomib is preferred for renal impairment: Bortezomib/dexamethasone regimens can be administered to patients with severe renal impairment and those on dialysis without requiring renal dose adjustment 1.
Third-agent options: Cyclophosphamide, thalidomide, anthracycline, or daratumumab can be added to bortezomib/dexamethasone without dose adjustment for renal function 1.
Common Pitfalls to Avoid
Do not attribute renal dysfunction solely to NSAIDs when plasma cell dyscrasia is present—the primary mechanism is light chain nephrotoxicity, though NSAIDs may contribute 1, 2.
Do not delay myeloma therapy while pursuing extensive diagnostic workup if the clinical picture is clear—rapid initiation of treatment is critical to prevent irreversible kidney damage 1.
Do not overlook alternative causes: Hypercalcemia, volume depletion, hyperuricemia, nephrotoxic medications, and intravenous contrast must all be considered and addressed as contributing factors 1.