An Elderly Woman With IgA Lambda Multiple Myeloma and Kidney Disease

A 92-year-old woman presented with a 6-month history of progressively worsening fatigue, weight loss, generalized bone pain, and dyspnea on exertion. The patient also noted increasing lower extremity edema. She had been using a wheelchair for the past 4 months as a result of severe low back and pelvic pain. The patient’s activities of daily living were homebound, with assistance from visiting nurses. Her history included osteoporosis; current medications were calcium with vitamin D and ibandronate.
 
The patient had no fever and was normotensive (102/64 mm Hg). Her pulse rate was regular (80 beats/min). She had significant temporal wasting, kyphosis of the spine, and 2+ peripheral edema. There was no lymphadenopathy. Her urine output was only 50 mL in first 24 hours of admission.
 
Laboratory studies found normocytic anemia (hemoglobin 5.6 g/dL and hematocrit 17.3%); hypoalbuminemia (albumin 1.9 g/dL); elevated total protein, 9.8 g/dL (normal range, 6.3 to 8.2 g/dL); and serum creatinine, 15.5 mg/dL. Corrected serum calcium was 10.1 mg/dL (normal range, 8.4 to 10.2 mg/dL). A skeletal survey found lytic lesions in the pelvis, sacrum, and calvarium (Figure). Serum protein electrophoresis (SPEP) showed abnormal bands in the gamma region (4.8 g/dL). Serum free light chain revealed an abnormal kappa/lambda ratio (0.7:16.2). Serum immunofixation demonstrated IgA/lambda monoclonal protein, and a diagnosis of IgA/lambda multiple myeloma (MM) was made.
 
After discussions with an oncologist and a nephrologist, the patient was willing to receive treatment. She underwent hemodialysis, palliative radiation for bone pain, and pulse dexamethasone. The patient was discharged, and plans were made for follow-up chemotherapy with melphalan.

Discussion
MM is a plasma cell dyscrasia that accounts for approximately 10% of hematologic malignancies in the United States. Annual incidence of the disease is approximately 4 to 5 per 100,000.¹ MM is a disease of the elderly: the incidence is 49 per 100,000 for people aged 80 years and older.

Most patients present with bone pain and fatigue/generalized weakness secondary to anemia as well as renal failure and recurrent infection. Less frequent symptoms include hyperviscosity syndrome, hypercalcemia, lymphadenopathy, fever, and spinal cord compression. In some patients, the disease may be asymptomatic and is diagnosed incidentally.

The hallmark of MM is the presence of a monoclonal (M) protein in the serum or urine. Serum and urine immunofixation, in conjunction with SPEP and urine protein electrophoresis (UPEP), help increase the sensitivity of M-protein detection. The most common type of M-protein is IgG (52%), followed by IgA (21%), light chain only (16%), IgD (2%), biclonal (2%), and IgM (<1%).² Serum free light chain assay, the newer generation of immunoassay that can detect low concentrations of monoclonal free light chains (kappa and lambda) in serum, has greater sensitivity than UPEP/urine immunofixation and can be used as an alternative method.³ In non-secretory myeloma (found in approximately 1% to 3% of patients), hypogammaglobulinemia may be the only finding. Our patient was found to have IgA lambda type MM.
 
Peripheral blood smear usually shows normocytic normochromic anemia with Rouleaux formation, caused by elevated serum protein levels. Bone marrow biopsy typically reveals 10% or more clonal plasma cells.

The characteristic findings on bone survey are multiple ‘‘punched-out’’ lytic lesions within the axial bone, such as skull, vertebral bodies, pelvis, or upper part of the extremities as seen in our case.⁴ Renal involvement is usually divided into 3 categories:

• Myeloma cast nephropathy: This is the most severe form caused by intratubular obstruction. Patients usually have overt renal insufficiency. Excessive amount of free light chain filtration from glomeruli has direct toxic effect on renal tubular cells and can cause intratubular cast formatin with Tamm-Horsfall protein leading to the obstruction.⁵
• Light chain deposition disease (previously known as primary amyloidosis): This milder form of myeloma-associated renal disease is characterized by heavy proteinuria (usually nephrotic range) as a result of free light chain deposition in the glomeruli.
• Tubular dysfunction: In some patients, the toxic effect of filtered light chains on renal tubules is limited to tubular dysfunction, resulting in signs of Fanconi syndrome such as proximal renal tubular acidosis, phosphate wasting, glycosuria, and aminoaciduria without a decline in glomerular infiltration rate.

Treatment for MM is individualized on the basis of a risk-benefit assessment and patient preference. The decision to undergo chemotherapy and the length of treatment are based primarily on risk stratification (determined by mutation analysis) and the patient’s eligibility for stem cell transplant; a less toxic drug regimen will preserve stem cells for transplant on completion of chemotherapy.⁶ Dialysis should not be initiated for the removal of free light chains but should be ordered for the usual indications (eg, fluid overload, hyperkalemia, and uremia). The evidence for the effectiveness of plasmapheresis in patients with myeloma-related acute kidney injury is controversial.^7,8 The experience with kidney transplant in MM is still limited to case series.⁹

References
1. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10-30.
2. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21-33.
3. Pratt G. The evolving use of serum free light chain assays in haematology. Br J Haematol. 2008;141:413-422.
4. D'Sa S, Abildgaard N, Tighe J, et al. Guidelines for the use of imaging in the management of myeloma. Br J Haematol. 2007;137:49-63.
5. Sanders PW. Pathogenesis and treatment of myeloma kidney. J Lab Clin Med. 1994;124:484-488.
6. Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk-stratification, and management. AmJ of Hematol. 2011;86:57-65.
7. Cohen DJ, Sherman WH, Osserman EF, Appel GB. Acute renal failure in patients with multiple myeloma. Am J Med. 1984;76:247-256.
8. Cserti C, Haspel R, Stowell C, Dzik W. Light-chain removal by plasmapheresis in myeloma-associated renal failure. Transfusion. 2007;47:511-514.
9. Heher EC, Spitzer TR, Goes NB. Light chains: heavy burden in kidney transplantation. Transplantation. 2009;87:947-952.