Managing Myeloma Kidney

It is estimated that, in 2005, multiple myeloma will be diagnosed in 15 980 persons and 11 300 persons will die of it, constituting 2% of all deaths from cancer (1). Although myeloma bone disease and anemia are the primary manifestations of the disorder, only 52% of patients have normal renal function at diagnosis. At presentation, the serum creatinine level is between 114 µmol/L (1.3 mg/dL) and 175 µmol/L (2.0 mg/dL) in 29% of patients and 176 µmol/L or more (≥2.0 mg/dL) in 19% of patients. Therefore, nearly 8000 patients per year will present their physicians with the challenging problem of managing the renal impairment associated with myeloma (2). In many instances, the renal insufficiency associated with multiple myeloma is related to several reversible problems due to volume depletion; hypercalcemia; and exposure to contrast material, nonsteroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors (3, 4). However, the most common finding is cast nephropathy (5, 6).

In cast nephropathy, filtered immunoglobulin light chains bind to a common site on Tamm–Horsfall protein. Tamm–Horsfall glycoprotein is secreted by the thick ascending limb of Henle loop and may function as a unique renal mechanism to regulate several potent cytokines, including interleukin-1 and tumor necrosis factor. Aggregation of these protein–protein complexes produces casts that physically obstruct tubule fluid flow, resulting in renal failure (7). Patients with a higher excretion of monoclonal immunoglobulin light chains in the urine have renal failure considerably more often than patients with lower excretion levels (8). Patients with myeloma that produces only intact immunoglobulins rarely develop cast nephropathy because the entire immunoglobulin molecule is too large to pass through the glomerular filter. Shortening the time in which the patients' kidneys are exposed to toxic light chains lowers the risk for permanent renal insufficiency. Therefore, reducing urinary light chain …