Understanding the Causes of Edema in Multiple Myeloma Patients

Edema, or abnormal fluid retention in the body's tissues, is a common yet complex symptom experienced by many individuals diagnosed with multiple myeloma. While swelling may appear to be a simple side effect, it often stems from several interrelated physiological disruptions caused directly or indirectly by the disease and its treatments. Below, we explore the primary underlying causes of edema in multiple myeloma patients, offering insight into how cancer-related processes impact overall fluid balance.

1. Hypoalbuminemia and Decreased Plasma Oncotic Pressure

Low levels of albumin (hypoalbuminemia) are one of the leading contributors to edema in multiple myeloma. In this condition, malignant plasma cells overproduce abnormal monoclonal proteins (M-proteins), particularly immunoglobulin fragments, which suppress the bone marrow's ability to generate normal proteins, including albumin. Albumin plays a critical role in maintaining oncotic pressure—the force that keeps fluid within blood vessels. When albumin levels drop, this pressure decreases, allowing fluid to leak into surrounding tissues, especially in the lower extremities and abdomen, resulting in visible swelling.

2. Kidney Dysfunction and Fluid Retention

Renal impairment is prevalent among multiple myeloma patients, affecting up to 40–50% at diagnosis. The kidneys can become overwhelmed by filtering excessive amounts of light chain proteins (Bence Jones proteins) produced by malignant plasma cells. This leads to tubular damage, reduced glomerular filtration rate, and impaired urine output. As the kidneys lose their ability to excrete sodium and water efficiently, fluid accumulates in the bloodstream and eventually leaks into interstitial spaces, contributing significantly to generalized edema. Early detection and management of kidney involvement are crucial for improving both comfort and long-term outcomes.

Monitoring Kidney Health in Myeloma Care

Regular assessment of serum creatinine, estimated glomerular filtration rate (eGFR), and urine protein levels allows healthcare providers to identify renal complications early. Hydration strategies, avoidance of nephrotoxic agents, and targeted therapies such as proteasome inhibitors can help preserve kidney function and reduce fluid buildup.

3. Cardiac Amyloidosis and Heart-Related Swelling

Another serious but underrecognized cause of edema is amyloid deposition in the heart tissue, known as cardiac amyloidosis. In some multiple myeloma cases, misfolded proteins accumulate in organs, especially the heart, disrupting its structure and function. This infiltration stiffens the heart muscle, impairing its ability to fill and pump effectively—a condition referred to as restrictive cardiomyopathy. As a result, blood backs up in the systemic circulation, increasing venous pressure and promoting fluid leakage into the legs, ankles, and lungs. Symptoms often include shortness of breath, fatigue, and pronounced peripheral edema.

4. Corticosteroid Therapy and Sodium Retention

Corticosteroids like dexamethasone are a cornerstone of multiple myeloma treatment regimens, frequently used in combination with other anti-cancer drugs. However, high-dose or prolonged steroid use comes with notable side effects, including sodium and water retention. These hormones influence the kidneys' handling of electrolytes by enhancing reabsorption of sodium through the distal tubules, which in turn pulls more water into the bloodstream. The increased intravascular volume raises hydrostatic pressure, encouraging fluid extravasation into tissues and manifesting as facial puffiness, leg swelling, or weight gain.

Managing Steroid-Induced Edema

Patients on corticosteroids should monitor their salt intake, elevate swollen limbs when possible, and stay physically active to promote circulation. Physicians may adjust dosing schedules or incorporate diuretics when clinically appropriate to alleviate symptoms without compromising cancer control.

5. Anemia and Its Role in Peripheral Edema

Chronic anemia is nearly universal in advanced multiple myeloma due to bone marrow infiltration by malignant cells and suppressed erythropoiesis. Severe anemia forces the cardiovascular system to compensate by increasing cardiac output. Over time, this strain can lead to high-output heart failure, particularly in older adults or those with pre-existing heart conditions. In such cases, the heart struggles to meet the body's oxygen demands, resulting in poor circulation and secondary fluid accumulation—often seen as bilateral leg swelling. Treating the underlying anemia with erythropoiesis-stimulating agents or transfusions may help reduce edema in select patients.

In summary, edema in multiple myeloma is rarely due to a single factor. It typically arises from a combination of hypoalbuminemia, renal dysfunction, cardiac amyloidosis, medication side effects, and anemia-related hemodynamic changes. A comprehensive, multidisciplinary approach involving oncologists, nephrologists, and cardiologists is essential for accurate diagnosis and effective symptom management. Recognizing the root cause of swelling enables personalized interventions that improve quality of life and support ongoing cancer therapy.