Effect of uremic toxin-indoxyl sulfate on the skeletal system

Publication date: September 2018Source: Clinica Chimica Acta, Volume 484Author(s): Wen-Chih Liu, Chia-Chao Wu, Paik-Seong Lim, Shiaw-Wen Chien, Yi-Chou Hou, Cai-Mei Zheng, Jia-Fwu Shyu, Yuh-Feng Lin, Kuo-Cheng LuAbstractChronic kidney disease-mineral bone disorders (CKD-MBD) exhibit abnormalities in the circulating mineral levels, vitamin D metabolism, and parathyroid function that contribute to the formation of a bone lesion. The uremic toxin, indoxyl sulfate (IS), accumulates in the blood in cases of renal failure and leads to bone loss. The bone and renal responses to the action of the parathyroid hormone (PTH) are progressively decreased in CKD in spite of increasing PTH levels, a condition commonly called PTH resistance. There is a high prevalence of low bone turnover or adynamic bone disease in the early stages of CKD. This could be due to the inhibition of bone turnover, such as in PTH resistance, reduced active vitamin D levels, diabetes, aluminum, and, increased IS. With an increase in IS, there is a decrease in the osteoblast Wnt/b-catenin signaling and increase in the expression of Wnt signaling inhibitors, such as sclerostin and Dickkopf-1 (DKK1). Thus, a majority of early CKD patients exhibit deterioration of bone quality owing to the action of IS, this scenario could be termed uremic osteoporosis. However, this mechanism is complicated and not fully understood. With progressive deterioration in the renal function, IS accumulates along with persistent PTH secreti...
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research