A 60-year-old man with a history of plasma cell dyscrasia was seen in a major hospital for progressive fatigue and a new diagnosis of acute kidney injury.
He had a serum creatinine level of 2.7 mg/dL, up from a previous serum creatinine measurement of 1.2 mg/dL. He denied any dysuria, hematuria, or foamy urine. He had no complaints of fevers, chills, SOB, chest pain, abdominal pain, or nausea, or vomiting. He had mild new leg edema for two weeks. He had no history of kidney stones and no recent use of nonsteroidal anti-inflammatory drugs. His blood pressure was 152/82. Auscultation revealed clear lungs. Legs show 1+ edema to shins bilaterally.
Labs include a hemoglobin of 9.9 g/dL, platelets of 207,000, albumin of 2.2 g/dL, a corrected calcium of 10.5 mg/dL. Urinalysis shows 30 protein, and no WBC or RBC. Urine protein to creatinine ratio equals 0.5.
A recent bone marrow biopsy demonstrated 20% lamda restricted plasma cells in the marrow. Serum protein electrophoresis and immunofixation showed a IgG lamda monoclonal protein band. Serum free light chain assay one month previously measured lambda light chain level of 1980 mg/dL. Since then the patient received bortezomib with steroids and new serum free light chain assay shows lambda level of 1380.
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The clinical history is consistent with a diagnosis of multiple myeloma, and the protein electropheresis and bone marrow biopsy demonstrate lambda light chain proliferation.
The kidney biopsy shows cast nephropathy. Many of the tubules show cast material of variable density by H&E, that is mostly negative by PAS (not shown). These casts also have an angulated, cracked morphology. Immunofluorescence studies (not shown) demonstrated positive lamda and negative kappa staining of the cast material. Congo red staining was negative.
Treatment of multiple myeloma includes steroids given with chemotherapeutic agents such as thalidomide, melphalan, cyclophosphamide, or bortezomib. Multiple myeloma patients can develop kidney failure. Types of kidney injury in myeloma include cast nephropathy, light chain deposition disease, amyloidosis, hypercalcemia-induced kidney injury, proximal tubular dysfunction, acute tubular necrosis, and other entities. Myeloma cast nephropathy is one of the more common causes of kidney injury in multiple myeloma.
Plasmapheresis has been used to treat myeloma cast nephropathy for some time, though this has not been without controversy. Results of studies assessing added benefit of plasmapheresis have been mixed, and chemotherapeutic options continue to advance. At least a few recent retrospective studies have demonstrated that plasmapheresis combined with steroids and bortezomib may accomplish over 50% reduction in serum free light chains with recovery of renal injury, with greater success and faster than medical treatment without plasmapheresis.
Answer: Bortezomib and dexamethasone and plasmapheresis
This case was prepared by Kevin T. Harley, MD, Assistant Clinical Professor of Medicine and Philip Carpenter, MD, Professor of Clinical Pathology at the University of California in Irvine.
- Burnette BL, Leung N, Rajkumar SV. Renal improvement in myeloma with bortezomib plus plasma exchange. N Engl J Med 2011;364:2365-2366.
- Leung N, Gertz MA, Zeldenrust SR, et al. Improvement of cast nephropathy with plasma exchange depends on the diagnosis and on reduction of serum free light chains. Kidney Int 2008;73:1282-1288.