Tamm-Horsfall Proteinuria

Abstract

A prolonged tubular nephrogram lasting hours to days has been seen in performing excretory urography in a group of infants and children. The patients shared in common some degree of oliguria but all were normotensive throughout the period of study and had calyces of normal caliber, indicating a precalyceal accumulation of contrast material. Large amounts of Tamm-Horsfall (T.H.) urinary mucoprotein (16) were subsequently found in several of the patients once diuresis occurred (Table I). This mucoprotein is of importance since it has been shown to form a viscid gel with resultant tubular blockage in conditions of oliguria or dehydration. It has been found not only in casts of patients with varying types of renal disease, but it even forms the main part of casts in multiple myeloma patients dying in renal failure (5–8). The clinical features and radiographs of the pediatric patients are reviewed in the light of known knowledge of T.H. protein (4–8, 13). Preliminary in vitro testing of this protein with currently used contrast media shows them capable of inducing T.H. precipitation, and this is presented in terms of its relationship to renal failure after excretory urography in adults with multiple myeloma (2, 3, 5, 9, 11, 15). Tamm-Horsfall Urinary Mucoprotein—Role in Renal Tubular Blockage by Casts While seeking viral inhibitory agents, Tamm and Horsfall (16) discovered in 1950 a urinary mucoprotein that was readily precipitated by relatively low sodium concentration. T.H. protein, subsequently found in every mammalian species, is a polymeric structure, rod-like in shape, with a molecular weight estimated at 7 × 106 (7). It is thought to be manufactured in the proximal nephron, probably in the proximal convoluted tubule or ascending limb of Henle (4), and is normally found in amounts up to 50 mg/liter of urine. It is excreted in increased amounts during exercise and in certain renal diseases that share in common relatively low urine flow, proteinuria, and cast formation (5, 7). The effect of dehydration or of hypertonic infusions is to concentrate the T.H. protein in the collecting tubules where it may go on to form aggregates that coalesce into viscid casts. McQueen et al. (4–8) showed T.H. protein rather than serum proteins to be the main constituent of casts that are the cause of renal tubular blockage in acute renal failure. These investigators in a series of reports suggested that renal tubular “necrosis” was less important than tubular blockage by casts in such patients with acute renal failure. They realized the application of these findings to renal failure in multiple myeloma and showed that Bence Jones protein readily causes T.H. protein to sludge in vitro and produces tubular obstruction. They identified T.H. protein in the casts found in multiple myeloma.