Troubles minéraux et osseux de la maladie rénale chronique (TMO-MRC)

Maintenance of calcemia and phosphatemia within a narrow physiological range is the result of a complex regulation based on exchanges of both calcium and phosphate between the kidney, the intestine and the skeleton. The kidney plays a crucial role in the balance of both ions by allowing a tightly adaptation between the renal elimination and the dietary intake of calcium and phosphate. Phosphocalcium homeostasis is largely regulated through an integrated hormonal system including parathyroid hormone and 1-25-dihydroxy-vitamin D. Our understanding of phosphocalcium metabolism has changed substantially in recent years thanks to the discovery of new actors such Fibroblast Growth Factor 23 and Klotho. The progressive reduction in the renal function as it is observed in the chronic kidney disease leads to serious disruption of mineral metabolism responsible for several metabolic disorders gathered under the term of « Chronic Kidney Disease - Mineral and Bone Disorders (CKD-MBD) ». This term encompasses several abnormalities including altered levels of calcium, phosphate, PTH and vitamin D metabolites, disturbances in bone turnover and bone mineralization, and development of vascular calcifications. Secondary hyperparathyroidism, whose mechanism is now better understood and whereby the phosphate retention plays a significant role, is one of the most important pathophysiological determinant involved in CKD-MBD. Numerous recent studies have shown that disturbances in mineral metabolism strongly contribute to the cardiovascular morbidity and mortality in CKD. In this review, we will first describe the main molecular mechanisms that contribute to regulate calcium and phosphate homeostasis and then we will focus on the pathogenesis of secondary hyperparathyroidism and its consequences on bone and vascular injuries. Finally, because biological measurements represent important tools in the diagnosis and the monitoring of CKD-MBD, we will point out the « Kidney disease improving global outcome (KDIGO) » recommendations on the biological parameters that can be measured.