OVERVIEW

What is Myeloma-Associated Nephropathy?

Myeloma-associated nephropathy refers to kidney damage caused by multiple myeloma, also known as renal impairment in multiple myeloma. Multiple myeloma is a malignant tumor among hematologic diseases.

The hallmark of this disease is the infiltration of the bone marrow by malignant plasma cells, leading to their excessive proliferation and the production of large amounts of abnormal immunoglobulins. These factors contribute to damage in multiple organs or tissues, with kidney damage—myeloma-associated nephropathy—being a common complication of multiple myeloma.

The causes are multifaceted, and it is often one of the primary fatal complications in myeloma patients. Timely diagnosis and appropriate treatment can improve the overall prognosis of patients with myeloma-associated nephropathy.

Is Myeloma-Associated Nephropathy Common?

In the United States, 4–5 people per 100,000 are diagnosed with multiple myeloma annually, accounting for about 1% of all cancers and 10% of hematologic malignancies. Its incidence has surpassed that of acute leukemia.

Myeloma-associated nephropathy is relatively common in multiple myeloma patients, occurring in over 50% of cases. Relevant data in China is currently lacking.

What Are the Types of Myeloma-Associated Nephropathy?

Based on the type of kidney damage, myeloma-associated nephropathy is classified into four types: myeloma cast nephropathy (or myeloma kidney), primary amyloidosis, light chain deposition disease, and renal tubular dysfunction.

The differences in kidney damage types primarily stem from the varying abnormal immunoglobulins secreted by malignant plasma cells.

• Myeloma Cast Nephropathy: This type accounts for 65% of cases. It occurs when abnormal immunoglobulins secreted by malignant plasma cells bind with proteins in the renal tubules, forming casts that obstruct and damage the tubules. It often presents as acute kidney failure without significant proteinuria.

• Primary Amyloidosis: This type accounts for 7% of cases. The abnormal immunoglobulins involved here are primarily λ light chains. After being engulfed by macrophages, these proteins undergo changes and deposit in tissues, forming fibrils that can be stained with Congo red dye. It typically manifests as nephrotic syndrome, with significant proteinuria.

• Light Chain Deposition Disease: This type accounts for 5% of cases. Similar to primary amyloidosis, but the abnormal immunoglobulins are κ light chains. These proteins deposit in tissues as granular deposits rather than fibrils and cannot be stained with Congo red. It also presents as nephrotic syndrome, with marked proteinuria.

• Renal Tubular Dysfunction: This occurs when abnormal immunoglobulins selectively damage the renal tubules without affecting the glomeruli. It manifests as Fanconi syndrome, characterized by renal glycosuria, renal tubular acidosis, hypophosphatemia, and hypouricemia.

SYMPTOMS

What are the common manifestations of myeloma-associated nephropathy?

• Manifestations of nephropathy:

  • Main manifestations include proteinuria;

  • Chronic tubular dysfunction, such as Fanconi syndrome (renal glycosuria, renal tubular acidosis, hypophosphatemia, hypouricemia), hypokalemia, polyuria, etc.;

  • Chronic renal failure, with anemia appearing earlier;

  • Acute renal failure, presenting as oliguria or anuria, often triggered by dehydration, contrast agents, infections, or medications, with a high mortality rate;

  • Urinary tract infections, with about one-third of patients experiencing recurrent cystitis or pyelonephritis, manifesting as fever, frequent urination, urgency, and dysuria;

  • Metabolic disorders, such as hypercalcemia and hyperuricemia, presenting as anorexia, nausea, polyuria, polydipsia, irritability, arrhythmia, or even coma.

• Extrarenal manifestations:

  • Mainly bone destruction, presenting as pain and susceptibility to fractures;

  • Anemia, manifesting as fatigue, palpitations, and pallor;

  • Infections, such as pneumonia, urinary tract infections, and sepsis, presenting as fever, etc.;

  • Bleeding tendencies, such as ecchymosis and epistaxis;

  • Hyperviscosity syndrome, presenting as dizziness, vertigo, tinnitus, blurred vision, numbness in extremities, and in severe cases, sudden confusion, heart failure, or dyspnea;

  • Polyneuropathy, manifesting as muscle weakness, numbness, and hypoesthesia;

  • Organ infiltration, such as hepatomegaly or soft tissue masses.

CAUSES

What Causes Myeloma-Associated Nephropathy?

The exact cause of multiple myeloma remains unclear.

• Myeloma-associated nephropathy results from kidney damage caused by abnormal globulins secreted by malignant plasma cells.

• Hypercalcemia, hyperuricemia, and hyperviscosity syndrome induced by multiple myeloma.

• The use of nephrotoxic drugs can also contribute to myeloma-associated nephropathy.

Who Is Prone to Myeloma-Associated Nephropathy?

This disease is associated with multiple myeloma, which predominantly affects middle-aged and elderly individuals. Therefore, myeloma-associated nephropathy is also commonly seen in this age group.

Is Myeloma-Associated Nephropathy Contagious?

This disease is not contagious.

Is Myeloma-Associated Nephropathy Hereditary?

There is currently no evidence to suggest that this disease is hereditary.

DIAGNOSIS

How to diagnose myeloma-associated kidney disease?

When diagnosing myeloma-associated kidney disease, doctors first confirm the diagnosis of multiple myeloma, followed by determining the presence of kidney damage.

What tests are needed for myeloma-associated kidney disease?

Generally, the following tests are required: complete blood count, peripheral blood smear, erythrocyte sedimentation rate (ESR), bone marrow aspiration, serum protein electrophoresis, serum immunoprotein testing, blood biochemistry, imaging (X-ray, CT, or MRI), urine protein testing, and urine protein electrophoresis.

• Complete blood count: Aids in diagnosis. All patients exhibit varying degrees of anemia, with decreased white blood cells and platelets in later stages.

• Peripheral blood smear: Aids in diagnosis. Rouleaux formation of red blood cells may be observed.

• Erythrocyte sedimentation rate (ESR): Aids in diagnosis. ESR is significantly elevated.

• Bone marrow aspiration: Confirms diagnosis. Myeloma cells or malignant plasma cells typically account for more than 10% of the sample.

• Serum protein electrophoresis and serum immunoprotein testing: Aids in diagnosis. Abnormal immunoglobulins produced by plasma cells can be detected.

• Blood biochemistry: Assesses kidney function and electrolytes (e.g., calcium, uric acid). Impaired kidney function may show elevated creatinine levels.

• Imaging (X-ray, CT, or MRI): Detects bone destruction, such as osteoporosis or fractures.

• Urine protein testing and urine protein electrophoresis: Aids in diagnosis.

Bone marrow aspiration is painful—is this test really necessary?

Bone marrow aspiration can indeed be uncomfortable, but it is essential for a definitive diagnosis.

The procedure is very safe. While there may be pain or soreness at the puncture site during and after the test, the discomfort typically subsides within a few days without lasting effects.

TREATMENT

Can Myeloma-Related Kidney Disease Heal on Its Own?

Multiple myeloma is a malignant tumor and will not improve without treatment, so myeloma-related kidney disease will not heal on its own either.

How Is Myeloma-Related Kidney Disease Treated?

The treatment of myeloma-related kidney disease primarily involves two aspects: treating the myeloma itself and managing kidney dysfunction.

• Treatment of Myeloma: Includes chemotherapy, radiation therapy, and hematopoietic stem cell transplantation.

• Treatment of Kidney Dysfunction includes:

• Symptomatic and Supportive Therapy:

  • Reducing blood calcium levels through hydration and bisphosphonates to correct hypercalcemia;
  • Using allopurinol to lower uric acid levels in the blood;
  • Maintaining blood volume to ensure kidney perfusion and prevent reduced urine output;
  • Administering alkali therapy in cases of acidosis;
  • Avoiding iodinated contrast agents whenever possible. With appropriate treatment, 26%–58% of patients with myeloma-related kidney disease may experience early recovery of kidney function.

• Renal Replacement Therapy: Such as plasmapheresis and dialysis.

• Anti-Myeloma Therapy: New chemotherapy regimens, including bortezomib, carfilzomib, thalidomide, lenalidomide, and other novel combination therapies, currently achieve satisfactory remission rates.

Does Myeloma-Related Kidney Disease Require Hospitalization?

Hospitalization is necessary during active treatment, but patients may not need to stay hospitalized during stable intervals.

Can Myeloma-Related Kidney Disease Be Cured?

This depends on whether the multiple myeloma itself can be cured.

DIET & LIFESTYLE

What should patients with myeloma-associated kidney disease pay attention to in daily life?

• Take precautions to prevent falls to avoid fractures;

• Practice daily protection and avoid crowded public places to prevent infections.

PREVENTION

How to Prevent Complications in Patients with Myeloma-Associated Kidney Disease?

For individuals over 40 years old with unexplained renal insufficiency, especially male patients; those presenting with multiple bone pain, hypercalcemia, fractures; or positive urine protein, the possibility of multiple myeloma should be considered. Early treatment is crucial, as 26%–58% of patients with myeloma-associated kidney disease may achieve early renal function recovery, thereby improving survival time.