What does it mean to have high free kappa (kappa light chains) and high free lambda (lambda light chains)?

From the Guidelines

High levels of both free kappa and free lambda light chains in the blood typically indicate increased production of immunoglobulins, which are antibody proteins made by plasma cells, and require further investigation to determine the underlying cause, which could be a benign condition or a serious blood disorder such as multiple myeloma or amyloidosis. This finding can occur in several conditions, most notably multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), amyloidosis, chronic lymphocytic leukemia, or certain autoimmune disorders 1. While both light chain types are elevated, what's particularly important is the kappa/lambda ratio, which should normally be between 0.26-1.65. If this ratio remains normal despite high absolute values, it suggests a polyclonal increase (meaning many different plasma cell populations are active) as seen in inflammatory conditions, infections, or kidney disease. However, if the ratio is abnormal, it may indicate a monoclonal process where a single abnormal plasma cell population is producing excess light chains of one type.

Some key points to consider in the evaluation of elevated free light chains include:

• The need for serum protein electrophoresis, immunofixation, and bone marrow biopsy to further investigate the cause of elevated free light chains 1
• The importance of monitoring the kappa/lambda ratio to determine if the increase is polyclonal or monoclonal 1
• The potential for elevated free light chains to be a marker of underlying conditions such as multiple myeloma or amyloidosis, which require prompt treatment 1
• The role of imaging studies and other diagnostic tests to evaluate the extent of disease and guide treatment decisions 1

Patients with elevated free light chains should be evaluated by a hematologist, as these findings could represent either benign conditions or serious blood disorders requiring treatment. The most recent and highest quality study on this topic is from 2021, which provides a comprehensive review of the management of patients with AL amyloidosis, including goals of therapy, current treatment guidelines, and treatment response monitoring recommendations 1.

From the Research

High Free Kappa and Lambda Light Chains

Having high free kappa (kappa light chains) and high free lambda (lambda light chains) can be an indicator of certain health conditions.

• The presence of high levels of both kappa and lambda light chains in the serum can be associated with multiple myeloma, a type of blood cancer characterized by the proliferation of malignant plasma cells in the bone marrow 2.
• In a study published in the journal Clinical Chemistry, the reference intervals for serum free kappa and free lambda immunoglobulin light chains were established, and it was found that the detection and quantification of monoclonal free light chains by nephelometry were more sensitive than immunofixation electrophoresis (IFE) in serum samples from patients with primary systemic amyloidosis and light-chain-deposition disease 3.
• Another study published in the journal Laboratory Medicine found that urine immunofixation electrophoresis and serum free light chain analyses can benefit the diagnosis of multiple myeloma in orthopedic patients with normal serum total proteins, creatinine, calcium, and hemoglobin 4.
• The role of serum protein electrophoresis in the detection of multiple myeloma was also studied, and it was found that this test can be used for the detection and quantification of monoclonal gammopathy and should be recommended as a preliminary test for suspected cases of multiple myeloma 5.

Diagnostic Implications

The diagnostic implications of having high free kappa and lambda light chains include:

• The need for further testing, such as bone marrow biopsy, to confirm the diagnosis of multiple myeloma 2.
• The use of serum free light chain measurements and serum and urine electrophoresis to monitor the response to therapy in patients with multiple myeloma 6.
• The importance of differentiating between multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS), as the management and prognosis of these two conditions are different 5.

Monitoring and Management

The monitoring and management of patients with high free kappa and lambda light chains include:

• Regular measurement of serum free light chain levels to monitor the response to therapy 6.
• The use of urine immunofixation electrophoresis and serum free light chain analyses to diagnose multiple myeloma in orthopedic patients with normal serum total proteins, creatinine, calcium, and hemoglobin 4.
• The consideration of autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide as part of the treatment plan for eligible patients with multiple myeloma 2.