Abstract
One of the defenses against nephrolithiasis is provided by macromolecules that modulate the nucleation, growth, aggregation and retention of crystals in the kidneys. The aim of the present study was to determine the behavior of two of these proteins, Tamm-Horsfall and uromodulin, in calcium oxalate crystallization in vitro. We studied a group of 10 male stone formers who had formed at least one kidney stone composed of calcium oxalate. They were classified as having idiopathic nephrolithiasis and had no well-known metabolic risk factors involved in kidney stone pathogenesis. Ten normal men were used as controls, as was a group consisting of five normal women and another consisting of five pregnant women. Crystallization was induced by a fixed supersaturation of calcium oxalate and measured with a Coulter Counter. All findings were confirmed by light and scanning electron microscopy. The number of particulate material deposited from patients with Tamm-Horsfall protein was higher than that of the controls (P<0.001). However, Tamm-Horsfall protein decreased the particle diameter of the stone formers when analyzed by the mode of the volume distribution curve (P<0.002) (5.64 +/- 0.55 microm compared to 11.41 +/- 0.48 microm of uromodulin; 15.94 +/- 3.93 microm and 12.45 +/- 0.97 microm of normal men Tamm-Horsfall protein and uromodulin, respectively; 8.17 +/- 1.57 microm and 9.82 +/- 0.95 microm of normal women Tamm-Horsfall protein and uromodulin, respectively; 12.17 +/- 1.41 m and 12.99 +/- 0.51 microm of pregnant Tamm-Horsfall protein and uromodulin, respectively). Uromodulin produced fewer particles than Tamm-Horsfall protein in all groups. Nonetheless, the total volume of the crystals produced by uromodulin was higher than that produced by Tamm-Horsfall protein. Our results indicate a different effect of Tamm-Horsfall protein and uromodulin. This dual behavior suggests different functions. Tamm-Horsfall protein may act on nucleation and inhibit crystal aggregation, while uromodulin may promote aggregation of calcium oxalate crystals.
Highlights
Human urine is almost always supersaturated with a mixture of various ions and salts, including calcium oxalate (CaOx), which is the most common component of kidney stones [1]
We studied a group of 10 male stone formers who had formed at least one kidney stone composed of calcium oxalate
Tamm-Horsfall protein decreased the particle diameter of the stone formers when analyzed by the mode of the volume distribution curve (P
Summary
Human urine is almost always supersaturated with a mixture of various ions and salts, including calcium oxalate (CaOx), which is the most common component of kidney stones [1]. Tamm-Horsfall protein (THP) is one of the main components of urinary proteins. It is a glycoprotein produced and secreted by the thick ascendant limb of the loop of Henle, being the most abundant protein in normal human urine, excreted in quantities of 20 to 200 mg/24 h [7,8]. THP of normal subjects inhibits the aggregation but has little effect on nucleation and growth of CaOx crystals [9]. THP isolated from the urine of recurrent stone formers sometimes becomes a promoter of CaOx aggregation due to a tendency to self-aggregation, which removes it from effective interaction with CaOx monohydrate crystals [11]
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