Relation Between PTH and the Risk of Mortality in CKD

Serum parathyroid hormone (PTH) is a well-recognized marker of parathyroid function and bone remodelling in chronic kidney disease (CKD) patients, both high and low levels being associated with poor outcomes. This may be due not only to the effect on CKD mineral and bone disorders (CKD-MBD) but also to the major ‘off-target’ effects in the cardiovascular system. As a matter of fact, an increasing number of observational cohort studies reported significant and independent associations between serum PTH levels and adverse outcomes including mortality in general population as in CKD, although the proof of a causal role for PTH in cardiovascular disease is still lacking. Therefore, normalization of PTH levels using either vitamin D, phosphate binders, calcimimetics or even parathyroidectomy might be an attractive option for the clinicians. However, studies trying to demonstrate a positive effect of PTH lowering therapies on cardiovascular or all-cause mortality revealed inconsistent results. Therefore, it has been proposed that PTH lowering medication should be used to improve the achievement of biochemical control of CKD-MBD and not with the purpose of reducing cardiovascular outcomes and/or improving survival. In addition to calcimimetics or vitamin D, moderate evidence data suggests a positive role of surgical parathyroidectomy in improving survival in dialyzed patients with severe hyperparathyroidism refractory to medical treatment. All in all, even if PTH remains one of the main target when it comes to treat CKD-MBD, there is still an opened debate if this translates into improved outcomes.