**10. Conclusions**

sHPT has significant clinical implications not restricted to the pathophysiology of some mineral and bone metabolism disorder. There is a substantial body of evidence that supports the role of PTH in the pathogenesis of abnormalities in cell function, contributing to several uremic findings in patients with CKD by increasing intracellular calcium. The presence of PTH receptors in di fferent tissues unrelated to calcium homeostasis may be the reason for such a number of nonclassical e ffects of severe sHPT.

The diversity of toxic e ffects involves myocardial dysfunction, cardiac hypertrophy, muscle weakness, osmotic fragility of erythrocytes, glucose intolerance, and abnormalities of the immune system (Figure 3). Moreover, there is evidence that PTX restores some of these organ dysfunctions, as shown in Table 1.

**Figure 3.** PTH-related manifestations on different target organs in uremic syndrome. Some studies have suggested the role of PTH in uremic syndrome through calcium-dependent and independent mechanisms. Among several toxic actions, it has been shown an association of high levels of PTH with myocardial hypertrophy and cardiovascular disease, nervous system disorders, development of sarcopenia, progression of chronic kidney disease, hematopoietic dysfunction, reduced insulin secretion by pancreatic beta-cells, increase of energy expenditure, "browning" of white adipose tissue, and high bone turnover with significant cortical compartment loss. CKD: chronic kidney disease.



Therefore, in view of the several adverse effects of high levels of PTH, a true uremic toxin, there is a need for closer monitoring for its levels in patients with CKD, in order to achieve more rigorous and early control of sHPT.

**Funding:** Drs Moyses and Elias are supported by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico). This financial support had no role in writing this review.

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