Multiple myeloma (MM) is a cancer originating in the plasma cells, a type of white blood cell in the bone marrow. These malignant plasma cells proliferate uncontrollably and produce excessive amounts of a single type of antibody component. Kidney involvement is a serious and frequent complication, often being the first sign of the underlying condition. Up to 50% of patients experience kidney dysfunction, which is a major factor affecting long-term outcomes and survival. The rapid onset of kidney issues often requires urgent medical intervention.
Mechanisms of Kidney Damage in Multiple Myeloma
Kidney damage primarily stems from the overproduction of monoclonal immunoglobulin free light chains (Bence Jones proteins). These small protein fragments are filtered by the kidney’s glomeruli in excess, overwhelming the reabsorptive capacity of the renal tubules. The severity of the kidney injury is directly related to the concentration and specific chemical properties of these circulating light chains.
The most common form of injury is Myeloma Kidney, also known as cast nephropathy, which accounts for the majority of acute kidney failure cases in MM patients. This occurs when the excessive light chains combine with Tamm-Horsfall protein, naturally secreted by the kidney tubules, to form large, obstructive casts. These obstructive plugs block the distal kidney tubules, leading to acute kidney injury and inflammation. The light chains are also directly toxic to the proximal renal tubules.
Another mechanism involves the misfolding and deposition of these light chains as insoluble fibers in a condition known as AL Amyloidosis. The light chains aggregate and deposit as amyloid fibrils in the glomeruli (the kidney’s main filtration units) and blood vessel walls. This deposition physically disrupts the normal architecture of the glomerulus, leading to significant protein loss in the urine and progressive loss of kidney function.
Elevated calcium levels (hypercalcemia) are also a contributing factor to kidney damage. MM often causes bone destruction, releasing calcium into the bloodstream. High calcium levels impair the kidney’s ability to concentrate urine, leading to dehydration, and also cause blood vessel constriction within the kidney, reducing blood flow. This combination of factors can directly damage the kidney tissue and worsen existing problems.
Recognizing Symptoms of Renal Impairment
The signs of renal impairment can be subtle and often overlap with general symptoms of the cancer itself. Fatigue is common as kidney function declines and waste products accumulate. Patients may also notice changes in urination habits, including producing foamy urine due to high protein content or experiencing a reduced output.
Swelling (edema) frequently develops as the kidneys lose the ability to excrete excess fluid and salt, often visible in the legs, ankles, and sometimes around the eyes. As kidney failure progresses, patients may experience nausea, loss of appetite, and a metallic taste. In severe uremia, the buildup of toxins can affect the central nervous system, leading to confusion or difficulty concentrating.
Diagnostic Tools for Assessing Kidney Function
Laboratory tests measure the extent of kidney damage and identify the specific cause. The primary measure of filtration capacity is the serum creatinine test, which measures a waste product in the blood normally cleared by the kidneys. This value is used to calculate the estimated Glomerular Filtration Rate (eGFR), which provides a clearer picture of how effectively the kidneys are filtering the blood.
Specific tests for abnormal proteins pinpoint the source of damage. Urine Protein Electrophoresis (UPEP) and immunofixation are performed on a 24-hour urine collection to identify and quantify the monoclonal light chains (Bence Jones proteins) being excreted. Measuring serum free light chains (FLCs) is also important, as high levels suggest cast nephropathy. A rapid reduction in FLC levels is directly associated with kidney recovery.
If the diagnosis remains unclear or light chain levels are not excessively high, a kidney biopsy may be necessary. This procedure involves taking a small tissue sample to examine under a microscope, differentiating cast nephropathy from AL amyloidosis or other light chain-related kidney diseases. The biopsy helps guide the most appropriate treatment strategy by confirming the exact pathological process.
Targeted Treatment Strategies for Renal Complications
The primary intervention for reversing kidney damage is the rapid reduction of monoclonal free light chains. This is achieved using effective anti-myeloma chemotherapy, such as regimens containing proteasome inhibitors like bortezomib, which rapidly shut down protein production. The speed of the anti-myeloma response is directly linked to the likelihood of kidney function recovery, especially in cast nephropathy.
Supportive care measures are implemented alongside anti-myeloma therapy to protect the kidneys. Aggressive hydration is employed to maintain a high urine flow, helping to flush the toxic light chain casts out of the kidney tubules and prevent new casts from forming. Hypercalcemia must be promptly managed with intravenous fluids and calcium-lowering medications like bisphosphonates to mitigate damage.
For acute kidney injury with very high light chain levels, some centers employ plasmapheresis (plasma exchange). This mechanical process filters the patient’s blood to remove circulating light chains, aiming for rapid clearance. However, its benefit remains a subject of debate, and it is typically used in conjunction with immediate, high-dose chemotherapy.
If kidney failure is severe and unresponsive, dialysis (renal replacement therapy) is initiated to sustain life by filtering the blood. Even when a patient requires dialysis, the focus remains on treating the underlying multiple myeloma with the goal of light chain reduction. If the myeloma is successfully controlled, there is a possibility of kidney function recovery, allowing the patient to eventually stop dialysis.