Citrate and calcium effects on Tamm-Horsfall glycoprotein as a modifier of calcium oxalate crystal aggregation

Abstract

We measured the effects of Tamm-Horsfall glycoprotein (THP) on calcium oxalate monohydrate (COM) crystal aggregation (Ac) in vitro as well as intrinsic viscosities (Vi) of THP at pH 5.7 and 200 mM NaCl and studied the effects of calcium and citrate on these parameters. THP were isolated from 24-h urines of seven male recurrent calcium stone formers (RCSF) and eight age-matched male healthy volunteers (N, normal). At basal conditions, RCSF-THP inhibited Ac by 28 +/- 10% and normal THP by 60 +/- 6% (P = 0.028). In the presence of calcium, increasing THP concentrations from 16 to 28 and 40 mg/l progressively lowered inhibition by RCSF-THP, but not by N-THP. At 40 mg/l, inhibition by N-THP was 27 +/- 9% vs. -43 +/- 8% by RCSF-THP (P = 0.001), i.e., all stone former THP promoted Ac. With an additional 3.5 mM of citrate, inhibition of Ac was 56 +/- 5% by normal and 34 +/- 6% by stone former THP (P = 0.021), and all seven stone former THP again inhibited Ac. Vi of RCSF-THP was higher than that of N at basal conditions (162 +/- 21 vs. 93 +/- 15 ml/g, P = 0.021) and in the presence of 5 mM calcium (352 +/- 54 vs. 118 +/- 17 ml/g, P = 0.001), i.e., RCSF-THP were more self-aggregated, but not when citrate was added (185 +/- 29 vs. 123 +/- 19 ml/g). (ABSTRACT TRUNCATED AT 250 WORDS)

Changes in urinary nanocrystallites in calcium oxalate stone formers before and after potassium citrate intake

“…TH protein promotes crystallite aggregation at lower pH but inhibits aggregation at higher pH. 19 Accordingly, in this study, the aggregation of urinary crystallites decreased after K 3 cit intake. Therefore, the increase in urinary pH was conducive to the prevention of CaOx stone formation.…”

“…After K 3 cit intake, the excretion and activity of TammHorsfall protein (TH protein) increased. 19 TH protein is also an anionic protein that enables the ζ of CaOx crystals to turn negative. 3.…”

SLC26A6 and NaDC-1 Transporters Interact to Regulate Oxalate and Citrate Homeostasis

“…In addition, once crystals are formed, citrate adsorbs to the crystal surfaces and suppresses their growth and attachment to epithelia. 13 By attaching to crystal surfaces, citrate also amplifies the protective effect of other stone inhibitors, such as the Tamm-Horsfall protein 14 and osteopontin. 15 At a pH of 7.4, citrate is mostly in the form of a tricarboxylic acid, but it can be reabsorbed only by the proximal tubule epithelium in its divalent form.…”

Adenosine triphosphate citrate lyase mediates hypocitraturia in rats.

“…Urinary citrate plays an important role in preventing formation of calcium-containing kidney stones by chelating calcium, directly inhibiting the crystallization and precipitation of calcium, and interacting with Tamm-Horsfal proteins to inhibit Ca-oxalate crystallization (1,2). Low urinary citrate occurs in approximately half of patients with renal stone disease (3).…”