Bone, Inflammation and the Bone Marrow Niche in Chronic Kidney Disease

What Do We Know?

Sandro Mazzaferro; Giuseppe Cianciolo; Antonio De Pascalis; Chiara Guglielmo; Pablo A. Urena Torres; Jordi Bover; Lida Tartaglione; Marzia Pasquali; Gaetano La Manna

Disclosures

Nephrol Dial Transplant. 2018;33(12):2092-2100. 

In This Article

Bone, Inflammation and the BM Niche in CKD: Final Considerations

The role of BM niche impairment in vascular disease in the setting of diabetes and atherosclerosis has been assessed and such impairment is also considered to be the first step in the process leading to the appearance of CCCs. This is undoubtedly the most intriguing, though still relatively uncharted area in the multifaceted scenario of the bone–vascular axis. The discovery of BM niche impairment in vascular disease is particularly important considering that the derangement of the bone–vascular axis is amplified by ageing and by CKD, diabetes and atherosclerosis, the incidence of which is constantly rising in the general population. It is possible to speculate that inflammation is the shared pathogenetic link, also bearing in mind the possible coexistence of diabetes, atherosclerosis and CKD, and the potential effects on bone remodelling and thus on BM niche function. Studies on impairment of the BM niche in CKD are still at an early stage. This is all the more surprising if we consider the crucial role that PTH, CaSR, FGF23, vitamin D, inflammatory cytokines and bone cells are acknowledged to play in regulating the expansion, mobilization and homing of HSPCs. The inflammatory burden and the impairment of bone remodelling inherent to the CKD-MBD syndrome most likely compromise the renewal of HSPCs and the provision of cell progenitors to vascular tissues, as well as promoting the development of cell subsets that express an osteogenic phenotype and thus probably affect the process of vascular calcification. Overall, like diabetes, CKD is a potential cause of BM niche dysfunction or mobilopathy and this urgently needs to be appreciated. Indeed, the metabolic derangements of mineral metabolism and the chronic inflammatory burden of renal insufficiency can predictably affect the function of the BM niche. Similarly, the different types of ROD (e.g. high- or low-turnover bone disease with resulting differences in bone cell numbers and activity) most probably impact the BM niche. Therefore, assessment of BM niche function in CKD patients could be important for the discovery of new pathways in the complex metabolic disturbance of uraemia and its heavy burden of morbidity and mortality.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....