What is the most likely cause of deterioration in kidney function in a patient with elevated creatinine, normal electrolytes, and 20% plasma cells on bone marrow biopsy?

Multiple Myeloma with Light Chain Cast Nephropathy

The most likely cause of this patient's kidney dysfunction is C: Accumulation of monoclonal light chains causing cast nephropathy. This patient presents with the classic triad of multiple myeloma (persistent bone pain, elevated creatinine, and 20% plasma cells on bone marrow biopsy), and renal insufficiency in this context is predominantly caused by light chain precipitation in the distal tubules 1, 2.

Pathophysiology of Myeloma Kidney

Light chain cast nephropathy is the primary mechanism of renal failure in multiple myeloma, occurring when monoclonal free light chains co-precipitate with Tamm-Horsfall protein in the distal nephron, causing tubular obstruction and subsequent kidney injury 2, 3. This process is distinct from other causes:

• The monoclonal light chains produced by malignant plasma cells are directly nephrotoxic to proximal tubules and form obstructive casts in distal tubules 2, 4
• Renal insufficiency is diagnosed at presentation in 20% of multiple myeloma patients, increasing to 40% in advanced disease 5, 1
• The NCCN guidelines specifically identify light chain cast nephropathy as the usual cause of renal insufficiency when creatinine is >2 mg/dL or eGFR <60 mL/min/1.73 m² 1

Why Other Options Are Less Likely

Acute tubular necrosis (Option A) would typically present with muddy brown casts on urinalysis and a history of hypotension, sepsis, or nephrotoxic drug exposure—none of which are mentioned in this case 1. While ATN can occur in myeloma patients, it is not the primary mechanism of renal failure in the setting of 20% plasma cells on bone marrow biopsy 2.

Kidney stones (Option B) are an extremely rare complication of multiple myeloma. While immunoglobulin free light chain kidney stones have been reported, they represent an unusual phenomenon requiring specific genetic predisposition for light chain crystallization 6. The clinical presentation of persistent back pain over 3 months is inconsistent with acute renal colic 6.

Waldenström macroglobulinemia (Option D) is a distinct lymphoplasmacytic lymphoma characterized by IgM monoclonal protein production, not the plasma cell proliferation seen in this patient's bone marrow biopsy 1. This diagnosis is incompatible with 20% plasma cells on bone marrow examination.

Diagnostic Confirmation

The NCCN guidelines recommend specific testing to confirm light chain cast nephropathy 1:

• Serum free light chain assay is essential for detecting and quantifying monoclonal light chains 1
• 24-hour urine collection for protein electrophoresis and immunofixation to detect Bence Jones protein (urinary light chains) 1, 7
• Renal biopsy may not be necessary if proteinuria predominantly consists of light chains with high serum free light chain levels and clear attribution to myeloma 1
• However, biopsy should be performed if there is no clear explanation for renal insufficiency to assess for alternative pathology such as monoclonal immunoglobulin deposition disease 1

Clinical Implications and Prognosis

Severe renal impairment and large amounts of proteinuria are associated with lower probability of renal recovery 2. However, with timely intervention:

• Renal function recovery occurs in more than two-thirds of patients with prompt institution of rapidly acting chemotherapy 4
• Cast nephropathy can resolve within weeks when serum free light chain concentrations fall rapidly 3
• Recovery of renal function improves overall survival and quality of life 4

Immediate Management Priorities

Bortezomib-containing regimens should be initiated as soon as possible to decrease production of nephrotoxic light chains 1. The NCCN guidelines specifically recommend:

• Bortezomib/dexamethasone regimens can be administered without renal dose adjustment, even in patients on dialysis 1
• If using two-drug bortezomib/dexamethasone, a third agent that doesn't require dose adjustment can be added (cyclophosphamide, thalidomide, anthracycline, or daratumumab) 1
• Bortezomib-based regimens may result in rapid reversal of renal failure in up to 50% of patients 2

Supportive care measures are critical 1, 2:

• Maintain high urine output (>3 L/day) to prevent further light chain precipitation 1
• Correct hypercalcemia and dehydration promptly 1, 2
• Avoid nephrotoxic medications including NSAIDs and intravenous contrast 1
• Address hyperuricemia if present 1

Common Pitfalls to Avoid

Do not delay chemotherapy while awaiting renal biopsy if the clinical picture clearly indicates myeloma cast nephropathy—early sustained reduction of circulating free light chains is the most important determinant of renal recovery 4. The evidence shows that rapid reduction of light chains to less than 5% of starting levels can lead to resolution of cast nephropathy within 6 weeks 3.

Do not assume plasmapheresis is beneficial—randomized studies have not confirmed benefit of plasma exchange for patients with severe kidney damage from myeloma 1. High cut-off hemodialysis dialyzers may potentially add clinical benefits, but outcomes of controlled trials are still awaited 4.