Tubular toxicity of filtered proteins

The mechanisms by which low-molecular-weight proteins filtered at the glomerulus might damage the kidney are reviewed. Despite a strong association between Bence-Jones proteinuria and impairment of renal function, many patients excrete light chains in large amounts and for long periods without evidence of renal abnormality. This critical paradox has still not been resolved despite suggestions, and investigations to explore them, that physicochemical properties of individual proteins might determine toxicity. The data suggest contributions, not mutually exclusive, from toxicity to proximal tubular cells via lysosomal uptake and from tubular obstruction by casts containing light chain and Tamm-Horsfall protein. The mechanisms, if any, of nephrotoxicity of haem proteins are equally uncertain.