concentrations of free light chains in the blood. At the same time, the amount of free light chains entering the urine will be decreased and will be zero if the patient stops producing urine (anuria). Conversely, urine concentrations of free light chains could increase if renal function improved in a multiple myeloma patient receiving treatment. This could account for the poor correlation frequently seen when urine and serum free light-chain concentrations are compared. The 500 mg of FLCs produced per day by the normal lymphoid system, however, flows through the glomeruli and is completely processed by the proximal tubules. If the proximal tubules of the nephrons are damaged or stressed (such as in hard exercise), filtered FLCs may not be completely metabolised and small amounts may then appear in the urine. Clinical use Serum free light-chain assays have been used in a number of published studies which have indicated superiority over the urine tests, particularly for patients producing low levels of monoclonal free light chains, as seen in nonsecretory multiple myeloma and AL amyloidosis. This is primarily because of the re-absorption of free light chains in the kidneys, creating a threshold of light chain production which must be exceeded before measurable quantities overflow into the urine. While there are a number of publications indicating that serum free light chain analysis is preferable to urine analysis at diagnosis, there is currently no consensus on whether urine tests for monitoring should be replaced. A series of studies, principally from the Mayo Clinic, have indicated that patients with an abnormal free kappa to free lambda ratio have an increased risk of progression to active myeloma from precursor conditions including monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma and solitary plasmacytoma of the bone. Abnormal free light chain production has also been reported to be prognostic of a worse outcome in multiple myeloma and chronic lymphocytic leukaemia. An abnormal light-chain ratio has been defined as a kappa to lambda chain ratio of less than 0.26 or more than 1.65. Guidelines In 2009, the International Myeloma Working Group published guidelines making recommendations of when serum free light-chain analysis should be used in the management of multiple myeloma. Diagnosis The serum free light-chain assay in combination with serum protein electrophoresis and serum immunofixation electrophoresis is sufficient to screen for pathological monoclonal plasmaproliferative disorders other than AL amyloidosis which requires all the serum tests as well as