**4. Conclusions**

Although the managemen<sup>t</sup> of CKD patients was significantly improved, we are still faced with a high rate of CV mortality. In this review, we tried to go from each of the candidate mineral disorder to the CV abnormalities (summarized in Table 2). The risks of each mineral disorder from the oldest to the newest one varied with each kind of cardiac abnormality, which means that it is a significant challenge to prevent all cardiac abnormalities, even if CKD-MBD control has been guided in strict compliance with the guidelines. Therefore, we do have CKD-MBD markers acting as toxins: phosphate, PTH, and FGF23, as present important targets for treatment. On the other side, cardioprotective CKD-MBD markers such as vitamin D and klotho could be additional and very helpful points to treat. Finally, the newest CKD-MBD biomarker sclerostin, that interplays in CKD-MBD developing pathways, is still debatable concerning its protective role or acting as a toxin and consequently increasing CV risk development.


**Table 2.** CKD-mineral and bone disorder (MBD) biomarkers, role in bone metabolism and the cardiovascular system.

Abbreviations: VC—vascular calcification; P—Phosphate; LVH—left ventricular hypertrophy; sHPTH—secondary hyperparathyroidism. → - brings to; ↓ decrease;↑increase.

Diagnosis of CKD-MBD in the early development of CKD (stages 1 and 2) would be of grea<sup>t</sup> importance in preventing CKD progression, its complications, and would improve patients' survival and quality of life.

Focusing on such toxins and/or their relevant mediators at early CKD stages might help to interfere over time with the vicious cycle of the cardio–renal connection, and improve the outcome of patients. Further clinical studies exploring the beneficial influence of therapy in CKD (vitamin D, iron replacement, anemia treatment, etc.) and the association to FGF-23 and sclerostin levels with the cardiovascular outcome, would be of grea<sup>t</sup> help in understanding the complex pathophysiological mechanism of CKD-MBD.

**Author Contributions:** Conceptualization, M.R.; A.F.; and G.S.; writing—original draft preparation, M.R.; A.F.; writing—review and editing, G.S.; supervision, G.S., M.R.; & A.F; contributed equally in the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
