Tamm-Horsfall uromucoprotein and the pathogenesis of casts, reflux nephropathy, and nephritides

This chapter is an attempt to organize and summarize a diverse literature concerning Tamm-Horsfall uromucoprotein. Importance of examination of urine sediment for casts and diagnostic classification of casts have been discussed. Despite a lack of understanding of its biologic function, clinicopathologic study of T-HM has implicated it as a component of a variety of disease states. It binds a number of proteins, including those on surfaces of bacteria and viruses. It inactivates enzymes of those organisms, possibly by reacting with ionic cofactors, such as divalent metals. Ionic binding of monovalent cations (e.g., Na+) and repulsion of anions, such as Cl-, suggest a role for T-HM in renal salt and water balance. The combination of T-HM with ions, including H+, and other materials that enhance gel formation may indicate an ion-exchange function. Gel (cast) formation in the lower nephron, however, may produce obstruction, which, following calcification, infection, or inflammation, could go on to produce stones, increase scarring, and augment reflux nephropathy. Pathogenetic roles in autoimmunity and disorders of mucus metabolism have also been speculated on.