Multiple myeloma (MM) is a cancer originating in the plasma cells, a type of white blood cell located in the bone marrow. These abnormal cells multiply uncontrollably and produce excessive amounts of a single type of antibody protein. Kidney involvement is a frequent and serious complication, affecting 20% to 50% of patients at diagnosis or during the disease course. The onset of kidney dysfunction significantly affects the overall outlook, making the preservation of renal function a priority in treatment. This deterioration results from a combination of direct protein toxicity and systemic metabolic imbalances caused by the cancer.
The Primary Mechanism: Light Chain Damage
The most common cause of kidney injury in multiple myeloma is Myeloma Cast Nephropathy (MCN), often referred to as “myeloma kidney.” This damage is directly caused by the overproduction of monoclonal immunoglobulin free light chains (FLCs), which are shed by the cancerous plasma cells. These small protein fragments are filtered out of the blood by the kidney’s filtering units, the glomeruli.
Normally, the kidney’s proximal tubules reabsorb and break down the small amount of FLCs naturally present. In MM, the sheer volume of FLCs overwhelms this reabsorptive capacity, causing the proteins to pass into the distal parts of the kidney tubule. Here, the FLCs interact with an acidic protein called Tamm-Horsfall glycoprotein (THP), which is secreted by the tubular cells.
This interaction causes the FLCs and THP to aggregate and solidify, forming large, obstructive plugs known as casts. These casts physically clog the kidney tubules, which process filtered fluid into urine. The resulting obstruction stops the flow of fluid, leading to a rapid decline in the kidney’s ability to filter waste, manifesting as acute kidney injury (AKI). Furthermore, the trapped casts and excess FLCs are directly toxic to the surrounding tubular cells, triggering local inflammation and long-term scarring. The severity of kidney damage often correlates directly with the amount of FLCs circulating in the blood.
Systemic Effects That Harm Kidneys
Damage from the free light chains is often compounded by systemic effects that further impair kidney function. The most significant of these is hypercalcemia, an abnormally high level of calcium in the blood. This occurs because the myeloma cells secrete substances that accelerate the breakdown of bone tissue, releasing calcium into the bloodstream.
High calcium levels harm the kidneys by causing the constriction of blood vessels within the kidney tissue. This vasoconstriction reduces blood flow to the kidneys, which lowers the filtration rate and starves the renal cells of oxygen. Hypercalcemia also directly damages the renal tubules, impairing their ability to concentrate urine and reabsorb water, often leading to dehydration.
Another contributing factor is hyperuricemia, or elevated levels of uric acid, which can arise from the rapid turnover of cancer cells. Although less common than MCN, high uric acid levels can precipitate in the renal tubules, forming crystals that cause an obstructive and inflammatory process. Dehydration plays a major role in worsening all these mechanisms because it concentrates the FLCs, calcium, and uric acid in the kidney tubules, making cast and crystal formation much more likely.
Identifying Kidney Impairment
Early detection of kidney impairment is important because prompt treatment can often reverse the damage. Patients may first notice generalized symptoms such as persistent fatigue, leg swelling (edema), or a decrease in urine produced. Shortness of breath can also occur due to fluid retention caused by the failing kidneys.
Diagnosis relies on specific blood tests that measure the kidney’s performance, such as serum creatinine and the estimated glomerular filtration rate (eGFR). Creatinine is a waste product that builds up in the blood when the kidneys are not filtering efficiently. The eGFR provides an estimate of the kidney’s actual filtration capacity.
A specific diagnosis of MM-related kidney disease requires specialized tests that measure the proteins produced by the myeloma cells. These include a serum free light chain (FLC) assay, which quantifies the toxic FLCs in the blood, and urine protein electrophoresis (UPEP), which identifies the presence of these proteins in the urine. The rapid and significant elevation of FLCs is a strong indicator that MCN is the cause of the acute kidney injury.
Therapeutic Approaches for Kidney Complications
The most effective strategy for managing kidney complications is to eliminate the root cause: the overproduction of toxic free light chains. This is achieved by aggressively treating the underlying multiple myeloma with anti-cancer therapy. Chemotherapy regimens that include a proteasome inhibitor, such as bortezomib, are frequently used because they can rapidly reduce the FLC levels.
Supportive care involves ensuring the patient is aggressively hydrated, often with intravenous fluids, to help flush the tubules and prevent the formation of new protein casts. Management of hypercalcemia is also necessary, typically requiring medications like bisphosphonates or denosumab to reduce bone breakdown and lower blood calcium levels.
In cases of severe acute kidney injury, specialized procedures may be employed to physically remove the FLCs from the bloodstream.
Specialized Procedures
High-cutoff hemodialysis (HCO-HD) uses a specialized filter to directly remove the small FLC proteins. Plasmapheresis (plasma exchange) involves removing the patient’s plasma and replacing it with donor plasma or a substitute. If the damage is severe and rapid, temporary dialysis may be necessary. The goal is achieving “dialysis independence” once the myeloma treatment has successfully lowered the light chain burden.