尿酸對草酸鈣結晶形成的影響

林俊廷^1,3、盧艷金^1,3、曾一修^1,2

亞東紀念醫院 外科部 ¹創傷科，²泌尿科; ³醫學研究部

The effect of uric acid on the calcium oxalate crystallization

Jun-Ting Lin^1,3, Yen-Chin Lu^1,3, Yi-Shiou Tseng^1,2

Divisions of Traumatology¹ and Urology², Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Department of Medical Research³, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Purpose:

Nearly one-third of patients with calcium stones have hyperuricosuria. But the association between hyperuricosuria and calcium stone formation is still debated. Previous studies showed that hyperuricosuria significantly enhanced kidney inflammation. TNF-α receptor (TNFR) plays an important role on the inflammation and regulates crystal adhesion proteins expression in the kidney. The aim of our study was to investigate that if uric acid increased calcium oxalate crystal aggregation and adhesion proteins via TNF signaling pathway in vitro.

Materials and Methods:

In the in vitro aggregation assay, uric acid (0.06mg/ml) was added to a buffer solution (NaCl 200mM+Sodium acetate 10mM, pH5.7) containing calcium oxalate (0.7mg/ml) at room temperature for 30 minutes. The amount of calcium oxalate aggregation were calculated under   microscopy and spectrometry. In addition, we applied calcium oxalate (100μg/ml) and uric acid (25mg/dL) on human kidney epithelial cells (HK-2) cells for 6 hours, and then Western blot was used to observe the expression of TNFR1/2 and adhesion proteins including Annexin II, OPN and CD44.

Results:

Our studies revealed that uric acid directly increased calcium oxalate crystal aggregation in vitro. In the HK-2 cell experiment, it was also found that uric acid could regulated the expression of TNFR1/2, and then increased the expression of crystal adhesion proteins such as Annexin II, OPN, and CD44.

Conclusions:

The experimental results showed that uric acid increased the ability of calcium oxalate crystal aggregation and promoted the formation of stones. Otherwise uric acid increase crystal adhesion proteins by regulating the expression of TNFR1/2, as a result of increasing the risk of kidney stone formation.