What is the most likely cause of impaired renal function in a 60-year-old male with persistent back pain unresponsive to Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), normal electrolyte levels, elevated creatinine levels, and 20% plasma cells in the bone marrow biopsy?

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, specifically light chain cast nephropathy (myeloma kidney). This patient presents with the classic triad of multiple myeloma: persistent back pain (suggesting bone involvement), elevated creatinine (renal impairment), and 20% plasma cells on bone marrow biopsy, which meets diagnostic criteria for symptomatic multiple myeloma 1.

Clinical Reasoning

Why Light Chain Cast Nephropathy is Most Likely

The combination of 20% plasma cells in bone marrow with acute kidney injury strongly indicates monoclonal light chain-mediated renal damage. 2 The pathophysiology involves:

• Plasma cell clones produce excessive monoclonal light chains (either kappa or lambda) that are freely filtered by the glomerulus due to their small molecular weight 2, 3
• These light chains precipitate in the distal tubules, forming obstructive casts with Tamm-Horsfall protein, causing tubular obstruction and acute tubular injury 2, 4
• High urinary free light chain excretion (>200 mg/day) with serum free light chain levels >150 mg/dL strongly suggests light chain cast nephropathy, even when serum levels may appear deceptively normal early in disease 2, 4

Why Other Options Are Less Likely

A. Acute Tubular Necrosis (ATN): While NSAIDs can cause ATN, this would be a secondary consideration. 5, 6 NSAIDs pose little threat in healthy individuals but can cause reversible decrements in renal function in volume-contracted states. 5, 7 However, the presence of 20% plasma cells makes light chain-mediated injury the primary mechanism, with NSAID use potentially contributing as a secondary insult. 4

B. Kidney Stones: This does not explain the bone marrow findings or the constellation of symptoms. Hypercalcemia from myeloma could theoretically cause stones, but this is not the primary mechanism of renal failure in this context. 1

D. Waldenström Macroglobulinemia: This is characterized by lymphoplasmacytic lymphoma producing IgM monoclonal protein, typically with ≥10% bone marrow involvement by lymphoplasmacytic cells (not plasma cells), and presents with hyperviscosity, lymphadenopathy, and neuropathy rather than lytic bone lesions and cast nephropathy. 1

Diagnostic Workup Required

Immediate laboratory evaluation should include: 2, 3

• Serum free light chain assay with κ:λ ratio determination - the single most important test to detect clonality and quantify light chain burden 2, 3
• 24-hour urine collection with protein electrophoresis and immunofixation to quantify Bence Jones proteinuria (may show kappa or lambda light chains at high levels) 2
• Serum protein electrophoresis (SPEP) and immunofixation to identify monoclonal protein 1, 2
• Renal biopsy should be strongly considered to definitively distinguish light chain cast nephropathy from other MGRS entities (light chain deposition disease, AL amyloidosis) 2, 3

Critical Management Priorities

Initiate bortezomib-containing regimens immediately to decrease production of nephrotoxic clonal immunoglobulin. 2, 4 The treatment goals are:

• Achieve at least 50-60% reduction in serum free light chains by day 12 of treatment - this is the most critical factor for renal recovery 2, 4
• Bortezomib/dexamethasone can be administered without dose adjustment in severe renal impairment and even in dialysis-dependent patients 2, 4
• Consider adding a third agent that doesn't require dose adjustment (cyclophosphamide, thalidomide, or daratumumab) 2

Essential Supportive Measures

• Immediately discontinue NSAIDs - continued use causes additional tubular injury and prevents renal recovery 4, 5
• Provide adequate hydration and consider urine alkalinization to reduce light chain precipitation 2
• Treat hypercalcemia if present 2

Common Pitfalls to Avoid

Every day of delay in starting effective antimyeloma therapy allows continued light chain production and progressive tubular damage that may become irreversible. 4 Key mistakes include:

• Attributing renal failure solely to NSAID toxicity and missing the underlying myeloma diagnosis 4
• Waiting for complete diagnostic workup before initiating treatment - start bortezomib-based therapy immediately if light chain cast nephropathy is strongly suspected 2, 4
• Using lenalidomide-based regimens without appropriate dose reduction in severe renal impairment causes treatment failure and toxicity 4
• Failing to measure serum free light chains serially to confirm adequate reduction allows continued renal injury 4