Finding an optimal range of parathyroid hormone (PTH) for individual treatment of chronic kidney disease (CKD) remains challenging, according to an article published in Kidney International.
Recent research has questioned the value of circulating PTH as a biomarker of outcomes such as bone disease, vascular calcification, and survival, as well as a therapeutic target. Pieter Evenepoel, MD, PhD, Jordi Bover, MD, PhD, and Pablo Urena Torres, MD, PhD, board members of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association) CKD-MBD Working Group, discussed the benefits and limitations of PTH. Their analysis revealed:
- High individual biologic variability in PTH levels
- Altered PTH metabolism: PTH fragments possibly exert effects that differ from intact PTH, for example. In addition, PTH may be oxidized to various degrees in CKD and thereby lose its biological activity.
- PTH resistance: Evidence points to downregulation of the PTH receptor and competing downstream signals.
Increases in the prevalence of low bone turnover disease indicate overtreatment of secondary hyperparathyroidism. While PTH tests perform satisfactorily at the extremes of the range, they are less beneficial in the middle zone.
Among the possible improvements in diagnostics, the authors discussed developing an assay that measures PTH signaling tone or sensitivity or finding a specific biomarker or panel that concurs with bone biopsy. As an adjunct, alkaline phosphatase testing has proven useful for assessing bone metabolism.
While the research community searches for solutions, PTH still has clinical utility. “It should be emphasized that no biomarker so far clearly proved to be superior to PTH in predicting bone metabolism in CKD,” Dr Evenepoel and his coauthors concluded. “More research is needed. Meanwhile, more frequent PTH testing, enabling PTH trends to be captured accurately, rather than abandoning PTH monitoring should remain the motto.”
The authors disclosed honoraria and other fees from various pharmaceutical companies.