Influence of Urinary Sialic Acid on Calcium Oxalate Crystal Formation

Abstract

Using seed crystal method, whole-urine method, and scanning electron microscopy, the inhibitory effects of sialic acid and osteopontin (OPN) on aggregation/growth of CaOx crystals were investigated. Using the seed crystal method, sialic acid showed an inhibitory effect on CaOx crystal aggregation/growth in a concentration-dependent manner, but almost no effect was observed using the whole-urine method. OPN showed an inhibitory effect on aggregation/growth in both experimental systems. The inhibitory effect of asialo-OPN on aggregation/growth was approximately 20% lower than that of OPN in the experiment using the seed crystal method and approximately 15% lower in the experiment using the whole-urine method. Scanning electron microscopy showed that OPN and sialic acid inhibit the aggregation of CaOx crystals. The above findings show that sialic acid accounts for about 15–20% of the involvement of OPN in CaOx crystallization.

Mechanisms of Stone Formation

“…[60;61] Desialylated THP has been isolated from stone matrix as well as the urine of stone formers. [62] A recent study of chemically desialylated THP isolated from a normal individual has demonstrated calcium oxalate crystal aggregation promotion compared with the unmodified molecule.…”

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

“…Desialylated proteins have been reported to reduce inhibitory activity of putative COM stone inhibitors, including prothrombin fragment-1 and osteopontin [28, 62]. Some investigators have reported reduced sialic acid contents in THP isolated from stone matrix [17, 30, 33, 52], while THP isolated from stone former urine has less sialic acid content than THP from healthy adults [26, 40].…”

“…Carboxylate groups of sialic acid contribute to the net anionic charge of THP, which influences intermolecular THP–THP interactions as well as protein adsorption on COM crystal surfaces [28, 29, 33, 61]. The role of native THP (n-THP) and desialylated THP (ds-THP) in the promotion and/or inhibition of both THP and COM aggregation has generated a degree of controversy.…”

Clinical informativity of postgenomic modification of uromodulin

“…Роль уромодулина в развитии уролитиаза широко обсуждается [1,2]. Ранее нами было показано, что уромодулин в различных условиях может существовать в двух основных олигомерных формах T&HE(7) с ММ 7 MD и T&HE(28) с ММ 28 MD [3] в зависимости от pH и концентрации одновалентных катионов в моче, а наличие в структуре уромодулина гликанов, содержащих сиаловые кислоты, обусловливает отрицательный заряд молекул уромодулина, который и приводит к их взаимному отталкиванию [3][4][5].…”