Kidney Failure

Many multiple myeloma patients may develop renal (kidney) insufficiency and/or renal impairment.

What Is Renal Impairment?

According to an article in the October 2017 issue of the Clinical Journal of Oncology Nursing Multiple Myeloma,  "Renal, GI, and Peripheral Nerves: Evidence-Based Recommendations for the Management of Symptoms and Care for Patients With Multiple Myeloma," "the kidneys are vital organs that filter the blood to remove waste materials, balance fluids and electrolytes, release hormones, and eliminate harmful chemicals from the body, including chemotherapeutic drugs. The terms renal impairment and renal insufficiency are often interchangeable and refer to the kidneys' inability to function at the full capacity." Many multiple myeloma patients may develop this complication during the course of their disease. For this reason, clinicians should routinely assess the renal function of myeloma patients.

Causes of Renal Impairment in Multiple Myeloma Patients

Renal impairment in patients with myeloma is caused mainly by the toxic effects of monoclonal light chains (a type of antibody) on glomeruli and renal tubules. Glomeruli are a cluster of capillaries (tiny blood vessels) around the end of the kidney tubule. The end of the kidney tubule is where waste products are filtered from the blood.

Cast Nephropathy

The most common form of injury to the kidneys in multiple myeloma is cast nephropathy. This complication occurs when an abundance of free light chains plug up the renal tubules. These excess free light chains form aggregates or casts. The casts lead to tubular obstruction and inflammation.  Approximately 85% of renal impairment in myeloma patients is related to monoclonal light chains

Comorbidities as Causes of Renal Impairment 

More than 15% of renal impairment in myeloma patients is the result of other causes. These causes include

• diabetes
• disease of the arteries
• complications of infection
• smoking

Other Myeloma-Related Factors That Impair Kidney Function

• hypercalcemia (high blood levels of calcium caused by myeloma-related bone breakdown)
• dehydration
• drugs that are toxic to the kidneys. These drugs include certain antibiotics, non-steroidal anti-inflammatory agents, and myeloma therapies that are excreted by the kidneys.
• contrast agents used in imaging studies (such as gadolinium).

Risk Factors for Renal Impairment

• advancing age
• development or worsening of other medical problems
• high multiple myeloma disease burden
• cumulative toxicity from treatment

Tests of Renal Function

All patients should have the following tests of renal function at diagnosis and at times of disease assessment:

• serum creatinine
• electrolytes
• urine protein electrophoresis (UPEP) of a sample from a 24-hour urine collection
• serum free light chain assay (Freelite test)

Treatment

Treating the myeloma should reverse kidney impairment, sometimes even in a patient whose kidneys fail or a patient who requires dialysis. However, longer-term kidney failure is usually not reversible. For dialysis patients, the use of anti-myeloma therapy along with high-cutoff hemodialysis membranes can potentially reverse renal impairment. High-cut hemodialysis membranes allow the removal of free light chains through their large pores. If high-cutoff hemodialysis is not available, plasma exchange may be beneficial.

The standard of care for patients with myeloma and renal impairment are Velcade-based regimens. Velcade can be safely combined with:

•  cyclophosphamide and dexamethasone
•  doxorubicin and dexamethasone
•  thalidomide and dexamethasone 

Patients with renal impairment may also take Kyprolis or Ninlaro, the other proteasome inhibitors.

Revlimid is excreted via the kidneys, so the dose of Revlimid must be adjusted according to the degree of renal impairment.

Supportive Care

Patients with suspected renal impairment must receive supportive care. This care includes hydration with intravenous (into the vein) fluids and rapid treatment for hypercalcemia. Clinical trials have shown the bone-modifying agent Xgeva (denosumab) is safer than the bisphosphonate Zometa for the treatment of myeloma-related hypercalcemia from bone disease in patients with severe renal impairment. Severe renal impaired is defined as creatinine clearance < 30 mL per minute.