free-light chains are normally monomeric, while lambda free-light chains tend to be dimeric, joined by disulphide bonds. Polymeric forms of both types of free light chain can also occur. Metabolism In normal individuals, free light chains are rapidly cleared from the blood and catabolised by the kidneys. Monomeric free light chains are cleared in 2–4 hours, and dimeric light chains 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 light chains 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 free light chains), 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 process 10–30 g of low-molecular-weight proteins per day, so under normal conditions no light chains pass beyond the proximal tubules. If immunoglobulin light chains are produced in sufficient amounts to overwhelm the proximal tubules' absorption mechanisms (usually due to the presence of a plasma cell tumour) the light chains enter the distal tubules and can appear in the urine (Bence Jones protein). The passage of large amounts of immunoglobulin light chains 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 (80 kDa) that aggregates into polymers of 20–30 molecules. It contains a short amino-acid sequence that can specifically bind to some free light chains. 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 light chains are filtered by the remaining nephrons leading to a cycle of accelerating renal damage with rising