A 64-year-old man is evaluated for a 1-month history of worsening fatigue and low back pain exacerbated by movement. He has no prior medical history and takes no medications. Vital signs are normal. Physical examination shows mucosal pallor and bony tenderness. Radiographs reveal lytic bone lesions. Laboratory studies show that hemoglobin is 8.8 g/dL, serum creatinine is 3.0 g/dL, and serum calcium is 10.8 g/dL. Urine dipstick is negative for protein, but quantitative measurement reveals elevated 24-hour urinary protein excretion. Urine electrophoresis is most likely to detect which of the following?
Multiple myeloma (MM) is a lymphoproliferative malignancy characterized by monoclonal plasma cell proliferation and production of monoclonal paraproteins (eg, immunoglobulins, chain fragments). MM should be suspected in elderly patients who have any combination of osteolytic lesions, hypercalcemia, anemia, or acute kidney injury (such as this patient). Other common symptoms include weight loss, constipation (due to hypercalcemia), fatigue, and recurrent infection.
Kidney disease in MM is largely due to light chain cast nephropathy (myeloma kidney). Intact immunoglobulins (eg, IgA, IgG, IgM) are too large to pass through the glomerulus, but a small amount of free light chains (eg, kappa, lambda) are freely filtered and resorbed in the proximal tubules. However in MM, the excessive quantities of free light chains exceed the resorptive capacity of the kidney. The filtered light chains then combine with Tamm-Horsfall proteins to form obstructive casts that cause tubular rupture and kidney injury.
Monoclonal paraproteins are not detected by urine dipstick (which detects only albumin), but quantitative protein concentrations (spot or 24-hour turbidimetric assay) will be elevated. Urine protein electrophoresis, immunofixation, or free light chain immunoassays can be used for diagnosis.
(Choices A, B, C, and D) MM can occasionally cause monoclonal immunoglobulin deposition disease, in which intact immunoglobulins or heavy and/or light chains deposit on the kidney basement membranes, resulting in glomerular disease and nephrotic syndrome. In this case, large intact immunoglobulins (and heavy chains) can enter the urine; however, albumin (which also passes through the injured glomerulus) would be detected on urine dipstick.
Educational objective:
Multiple myeloma should be suspected in elderly patients who have any combination of osteolytic lesions, hypercalcemia, anemia, or acute kidney injury. Renal disease is most commonly caused by light chain cast nephropathy, in which free light chains form obstructive casts in the renal tubules. Monoclonal paraproteins are not detected by urine dipstick (which detects only albumin), but both spot and 24-hour protein concentrations will be elevated.