Secondary hyperparathyroidism in chronic kidney disease: update on pathophysiology and new treatment targets

Secondary hyperparathyroidism remains a universal complication of chronic kidney disease (CKD), yet evidence-based treatment targets for parathyroid hormone (PTH) are lacking. This review revisits the pathophysiology of secondary hyperparathyroidism with emphasis on PTH as a master regulator of both calcium and phosphate homeostasis and discusses emerging treatment targets beyond PTH.

Recent data reinforce the role of phosphate burden as a central driver of hyperparathyroidism in CKD. At the same time, publications from recent years highlight substantial heterogeneity in skeletal responsiveness to PTH with discordance between PTH levels and bone turnover. Observational data continue to demonstrate nonlinear associations between PTH levels and patient-relevant outcomes, while interventional trials defining optimal PTH targets remain scarce. Recent consensus statements propose the use of nonkidney-cleared bone turnover markers as a supplemental noninvasive tool to better assess skeletal remodeling activity and guide treatment decisions.

PTH levels do not adequately reflect skeletal remodeling in CKD. A broader approach that considers biochemical bone turnover markers alongside PTH may allow a more individualized management strategy. Future studies should focus on defining optimal treatment targets and should include clinically important and patient-relevant, rather than biochemical, outcomes.