Pathophysiology of Tamm-Horsfall protein

Tamm-Horsfall protein (TH protein), a renal epithelial glycoprotein, was isolated originally from human urine [1, 2]. This membrane glycoprotein has several unusual physicochemical characteristics that may determine its role in normal tubular function in its distal nephron site of synthesis and in pathologic conditions. Variations of the ionic environment in the physiologic ranges observed in urine or within the kidney cause remarkable changes in the physical properties of TH protein. These reversible changes are the basis for the standard method of TH protein isolation and purification by repeated precipitations in 0.58M sodium chloride solution and dialysis against distilled water, originally described by Tamm and Horsfall [1, 2]. Increasing concentrations of TH protein, electrolytes, or hydrogen ions within physiologic limits causes aggregation of TH protein molecules, leading to increased viscosity and gel formation [3, 4]. When these conditions are met within the nephron, hyaline casts are formed. TH protein is the primary constituent of hyaline casts, according to immunochemical [5, 6] and biochemical composition [6] and immunofluorescent microscopy [7, 8]. McQueen first established that the matrix of casts was predominantly TH protein by showing that hyaline casts from a nephrotic patient contained 50 times more TH protein than they did albumin [5]. More than two decades before the classical isolation by Tamm and Horsfall [1], a remarkable description of the solubility characteristics of TH protein was provided by Thomas Addis [9]