Bacterial infection has long been recognized to contribute to struvite urinary stone deposition; however, its contribution to the development of chronic kidney stones has not been extensively investigated. In this study, we hypothesized another possible method of bacteria contributing to the formation of calcium oxalate (CaOx) that accounts for the biggest part of the kidney stone. Bacteria may play important roles by influencing renal calcium-related ion channel activities, resulting in chronic inflammation of the kidney along with the rapid aggregation of stones. We examined the correlation among infection-promoted CaOx kidney stones and alterations in calcium-related ion channels in an animal model with experimentally induced Proteus mirabilis and foreign-body infection. After infecting the bladder for 7 days, the data demonstrated that the stones were presented and induced severe renal tubular breakage as well as altered levels of MCP-1, COX-2, OPN, and TRPV5 expression, reflecting responses of the kidney ion channels. MCP-1, OPN, and TRPV5 expression were significantly downregulated over time, indicating the chronic inflammation phase of the kidney and accelerated aggregation of CaOx crystals, respectively, while COX-2 exhibited no differences. These results indicated that bacterial infection is considerably correlated with an alteration in renal calcium-related ion channels and might support specific targeted calcium-related ion channel-based therapeutics for urolithiasis and related inflammatory renal damage.
American journal of physiology. Renal physiology. 2019 Sep 11 [Epub ahead of print]
Juin-Hong Cherng, Yu-Juei Hsu, Chuan-Che Liu, Shou-Hung Tang, Dewi Sartika, Shu-Jen Chang, Gang-Yi Fan, Sheng-Tang Wu, En Meng
Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taiwan., Department of Cardiology, Cardinal Tien Hospital, Taiwan., Department of Surgery, Tri-Service General Hospital, Taiwan., Department of Internal Medicine, Tri-Service General Hospital, Taiwan., Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan., Division of Urology, Department of Surgery, Tri-Service General Hospital, Taiwan.