From the Guidelines
Multiple myeloma commonly causes proteinuria due to the overproduction of monoclonal immunoglobulins by malignant plasma cells, and management focuses on treating the underlying multiple myeloma with appropriate chemotherapy regimens, maintaining hydration, avoiding nephrotoxic medications, and monitoring renal function, as recommended by the NCCN guidelines 1.
Key Points
- Proteinuria in multiple myeloma typically consists of light chains (Bence Jones protein) that can be detected in urine protein electrophoresis.
- The excess light chains overwhelm the kidney's reabsorption capacity, leading to their appearance in urine.
- In multiple myeloma, proteinuria can manifest as part of myeloma kidney disease, which includes cast nephropathy, light chain deposition disease, or amyloidosis.
- Patients should undergo 24-hour urine protein collection, serum free light chain assay, and serum and urine protein electrophoresis with immunofixation to characterize the proteinuria.
- Early intervention is crucial as renal impairment is a significant cause of morbidity and mortality in multiple myeloma patients, and proteinuria typically improves with successful treatment of the underlying myeloma, as supported by studies such as 1 and 1.
Diagnosis and Workup
- The initial diagnostic workup in all patients should include a history and physical examination, as well as baseline laboratory studies such as CBC, blood urea nitrogen, serum creatinine, and liver function tests, as outlined in the NCCN guidelines 1.
- Magnetic resonance imaging (MRI) can be useful in detecting occult lesions and predicting rapid progression to symptomatic myeloma in patients with smoldering (asymptomatic) myeloma, as recommended by the International Myeloma Workshop Consensus Panel 3 1.
Treatment and Follow-up
- Treatment of multiple myeloma typically involves chemotherapy regimens such as bortezomib, lenalidomide, and dexamethasone combinations.
- Patients with measurable monoclonal protein in serum should have electrophoretic studies and quantitative immunoglobulins to assess response, and those with light chain myeloma should have 24-hour urine collection with total protein and urine electrophoresis to quantify Bence Jones proteinuria, as recommended by the International Myeloma Workshop Consensus Panel 3 1.
- Bone marrow aspiration and/or biopsy are indicated to establish complete response, which has prognostic implications for longer duration of response and survival, as supported by studies such as 1 and 1.
From the Research
Multiple Myeloma and Proteinuria
- Multiple myeloma is a hematologic malignancy that can cause kidney injury, leading to proteinuria 2.
- Proteinuria is a common complication in multiple myeloma patients, with approximately 19% of patients having acute kidney injury at the time of presentation 2.
- The International Myeloma Working Group recommends measuring serum creatinine, estimated glomerular filtration rate, and free light chains, as well as 24-hour urine total protein, electrophoresis, and immunofixation to evaluate renal function in multiple myeloma patients 3.
- Renal biopsy may be necessary if non-selective proteinuria or involved serum free light chains are detected 3.
- Bortezomib-based regimens are a cornerstone of management for patients with multiple myeloma and renal impairment at diagnosis 3.
- New quadruplet and triplet combinations, including proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies, can improve renal and survival outcomes in both newly diagnosed patients and those with relapsed or refractory disease 3.
- Urinary proteins, such as IgG, alpha(1)-microglobulin, and albumin, can be reliable and sensitive markers for detecting renal damage in multiple myeloma patients 4.
- These proteins can correlate with clinical parameters, such as bone marrow plasmacytosis and beta(2)-microglobulin, and can be used to monitor renal function in multiple myeloma patients 4.
Diagnosis and Management
- Evaluation of patients with possible multiple myeloma includes measurement of hemoglobin, serum creatinine, serum calcium, and serum free light chain levels, as well as serum protein electrophoresis with immunofixation and 24-hour urine protein electrophoresis 2.
- The Revised International Staging System combines data from serum biomarkers to assess estimated progression-free survival and overall survival 2.
- Standard first-line therapy for multiple myeloma consists of a combination of an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone, which can be associated with median progression-free survival of 41 months 2.
- Induction therapy with an injectable proteasome inhibitor, an oral immunomodulatory agent, and dexamethasone, followed by treatment with autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide, is considered standard care for eligible patients 2, 5.