Many multiple myeloma patients may present with renal insufficiency and/or renal impairment.
What Is Renal Impairment?
According to an article titled "Renal, GI, and Peripheral Nerves: Evidence-Based Recommendations for the Management of Symptoms and Care for Patients With Multiple Myeloma" in the October 2017 issue of the Clinical Journal of Oncology Nursing 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 present this complication during the course of their disease. For this reason, myeloma patients' renal function should be routinely assessed by their clinicians.
Causes of Renal Impairment in Multiple Myeloma Patients
Renal (kidney) impairment in patients with myeloma is caused mainly by the toxic effects of the monoclonal light chains on glomeruli (a cluster of capillaries around the end of the kidney tubule, where waste products are filtered from the blood) and renal tubules. The most common form of injury to the kidneys in multiple myeloma is cast nephropathy, the plugging up of renal tubules by overwhelming free light chain production. Excess free light chains form aggregates or casts, leading to tubular obstruction and inflammation.
Although approximately 85% of renal impairment in myeloma patients is related to monoclonal light chains, more than 15% of renal impairment in myeloma patients is the result other causes, such as diabetes, artery disease, complications of infection, or even smoking.
Other myeloma-related factors that impair kidney function are hypercalcemia (high blood levels of calcium caused by myeloma-related bone breakdown), dehydration, drugs that are toxic to the kidneys (such as certain antibiotics, non-steroidal anti-inflammatory agents, and myeloma therapies that are excreted via the kidneys), and 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
- Urine protein electrophoresis (UPEP) of a sample from a 24-hour urine collection
- Serum free light chain assay (Freelite test)
Treating the myeloma will reverse kidney impairment, sometimes even in a patient who has been in kidney failure and on dialysis (although longer-term kidney failure is usually not reversible). For dialysis patients, the combined use of antimyeloma therapy along with high-cutoff hemodialysis membranes, which allow the removal of free light chains through their large pores, has produced encouraging results in the reversal of renal impairment. If high-cutoff hemodialysis is not available, plasma exchange may be of benefit.
Velcade-based regimens have been considered the standard of care for patients with myeloma and renal impairment. Velcade can be safely combined with cyclophosphamide and dexamethasone, doxorubicin and dexamethasone, or thalidomide and dexamethasone. The other proteasome inhibitors, Kyprolis and Ninlaro, can also be administered to patients with renal impairment.
The dosing of Revlimid, which is excreted by the kidneys, must be adjusted according to the degree of renal impairment.
Supportive care is mandatory for all patients in whom renal impairment is suspected. This includes hydration with intravenous fluids and rapid treatment of hypercalcemia. Clinical trial data from a study comparing the bone-modifying agent denosumab (Xgeva) to the bisphosphonate Zometa in multiple myeloma patients demonstrated that Xgeva is safer for treatment of myeloma-related hypercalcemia from bone disease in patients with severe renal impairment (defined as creatinine clearance < 30 mL per minute) than is Zometa.