In normal individuals,<unk><unk><unk> s are rapidly cleared from the blood and catabolised by the kidneys. Monomeric<unk><unk><unk> s are cleared in 2–4 hours, and dimeric<unk><unk> s in 3–6 hours. Removal may be prolonged to 2–3 days in people with complete renal failure. Human kidneys are composed of approximately half a million nephrons. Each nephron contains a glomerulus with basement membrane pores that allow filtration of immunoglobulin<unk><unk> s and other small molecules from the blood into the proximal tubule of the nephron. Filtered molecules are either excreted in the urine or may be specifically re-absorbed. Protein molecules that pass through the glomerular pores are either absorbed unchanged (such as albumin), degraded in the proximal tubular cells and absorbed (such as<unk><unk><unk> s), or excreted as fragments. This re-absorption is mediated by a receptor complex (megalin/cubulin) and prevents the loss of large amounts of protein into the urine. It is very efficient and can process10–30g of low-molecular-weight proteins per day, so under normal conditions no<unk><unk> s pass beyond the proximal tubules. If immunoglobulin<unk><unk> s are produced in sufficient amounts to overwhelm the proximal tubules' absorption mechanisms (usually due to the presence of a plasma cell tumour) the<unk><unk> s enter the distal tubules and can appear in the urine (Bence Jones protein). The passage of large amounts of immunoglobulin<unk><unk> s through the kidneys may cause inflammation or blockage of the kidney tubules. The distal tubules of the kidneys secrete large amounts of uromucoid (Tamm–Horsfall protein). This is the dominant protein in normal urine and is thought to be important in preventing ascending urinary infections. It is a relatively small glycoprotein (80kDa) that aggregates into polymers of 20–30 molecules. It contains a short amino-acid sequence that can specifically bind to some<unk><unk><unk> s. Together they can form an insoluble precipitate which blocks the distal part of the nephrons. This is termed "cast nephropathy" or "myeloma kidney" and is typically found in patients with multiple myeloma. This can block the flow of urine causing the death of the respective nephrons. Rising concentrations of<unk><unk> s are filtered by the remaining nephrons leading to a cycle of accelerating renal damage with rising concentrations of<unk><unk><unk> s in the blood. At the same time, the amount of<unk><unk><unk> s entering the urine will be decreased and will be zero if the patient stops producing urine (anuria). Conversely, urine concentrations of<unk><unk><unk> s 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<unk> <unk><unk><unk>  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.
Serum free light-chain measurement
Bone biopsy
Serum protein electrophoresis
Renal biopsy
Skin biopsy
Scanning laser ophthalmoscopy
Retinoscopy
Urine protein/creatinine ratio