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EAU 2018: Osteopontin Antibody in the Suppression of Kidney Crystal Formation in a Mice Model of Metabolic Syndrome

Copenhagen, Denmark (UroToday.com) Dr. Sugino, clinical urologist from the Nagoya City University in Nagoya, Japan, introduced his study regarding the relevance of Osteopontin (OPN) in the formation of kidney stones. In previous research conducted at the center, it was reported that metabolic syndrome (MetS) promotes kidney stone formation through paracrine signaling pathways between adipocytes and various adipocytokines. OPN has been shown to be expressed in the early stages of kidney stone formation, which the presenter believes may lead to potential drug therapies to prevent stone formations. In previous experimentation, OPN knockout mice (OPN-/-) who were treated with glyoxylic acid (GOX), a chemical known to promote stone formation, showed little nephrolithiasis formation. The antibody for OPN was even shown to inhibit crystallization of stones in wildtype mice. Using this previous information, Dr. Sugino and his team attempted to evaluate whether kidney stone formation is suppressed by OPN antibody in mice with MetS.

In this particular study, 8-week-old male MetS mice were given daily injections of GOX (50 mg/kg) to attempt to induce renal crystallization for 6 days. The antibody used to attempt to knockout OPN function was antimurine monoclonal antibody clone 35B6. This was injected intraperitoneally on days 0, 3, and 6. A separate group of mice were administered an IgG antibody to act as a control. On days 1, 4, and 7, mice were sacrificed and renal specimens were collected. Following subject testing, analysis points that were collected consisted of body weight, serum biochemistries, 24 hour urine, renal crystal deposition/amount, and arteriosclerosis screening.

Following data collection, it was shown that antimurine OPN antibody was successful in suppressing the crystal formation within the MetS mouse model. Though the original hypothesis was supported by this data, the researchers discovered something unexpected from their analyses. It was also shown that serum adiponectin levels increased in the OPN antibody treatment groups. Adiponectin has been shown in previous literature to have the possibility of inhibiting arteriosclerosis. This molecule has also been shown in previous studies to have qualities such as anti-inflammatory, anti-apoptotic, and even improve cell function, all of which inhibits the formation of renal calculi. In conclusion, Dr. Sugino and colleagues discovered that OPN antibody treatment does indeed have the potential to not only suppress renal stone formation, but also potentially reduce metabolic syndrome such as arteriosclerosis.

Speaker: T. Sugino

Authors: Sugino T., Taguchi K., Unno R., Tanaka Y. , Hamamoto S. , Ando R., Okada A., Mogami T., Tozawa K, Kohri K., Yasui T.

Written by: Zachary Valley, Department of Urology, University of California-Irvine, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark