Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Abstract

or Article Brief (if supplied by editors): As a 'Therapy in Practice' article, we would like this to provide a succinct, up-to-date clinically orientated guide to the optimum management of secondary hyperparathyroidism in patients with chronic kidney disease. The review should include an appropriate background to the development of SHPT. It should focus primarily on pharmacological treatments but as appropriate, non-pharmacological approaches (dietary, surgical) may be discussed to fully place pharmacological therapy in context. Submission date: 31 st March 2016Word count: 4156 Compliance with Ethical StandardsFunding and conflict of interest statement from each author: Takeaway messages from the article SHPT is associated with adverse outcomes in CKD and dialysis patients  Optimum PTH level is unclear in pre-dialysis CKD and the recommended range is wide for dialysis patients.  Management of SHPT is largely pharmacological focussing on lowering PTH  PTH lowering treatment has not shown improved cardiovascular risk, fractures and mortality. AbstractSecondary hyperparathyroidism (SHPT) is a common complication of CKD and is part of the chronic kidney disease-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality, thus SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between predialysis CKD and dialysis patients which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options.

Pharmacokinetic and Pharmacodynamic Characteristics of Subcutaneously Applied PTH-1-37

“…However, there are meanwhile well established therapeutic options to cope with this condition such as reducing phosphate reupsorption by phosphate binders, vitamin D treatment, treatment with calimimetitics such as cinacalcet and finally removal (partially or total) of the parathyroid gland [29]. However, the opposite condition is also observed in CKD.…”

Secondary hyperparathyroidism in patients with chronic kidney disease: Diagnosis, pharmacological and surgical treatment

“…Hyperphosphatemia contributes to hypocalcemia by binding to ionized Ca in the serum as Ca-phosphate and by directly inhibiting renal 1-alpha hydroxylase. Reduced 1.25-(OH) 2 vit D3 levels contributes to SHPT by direct hypocalcemia and activation of PTH synthesis by vit D receptor (VDR) on parathyroid cells (14,17,18).…”

“…FGF23 levels start to rise in early CKD stage 2 ( Table-2), prior to elevations of phosphate and PTH. FGF23 maintains normal serum phosphate via two 2 main mechanisms (17,18). FGF23 decreases phosphate reabsorption in the proximal tubules and reduces 1.25(OH) 2 vit D3 levels through decreased expression of 1-alpha hydroxylase (19).…”

“…The net effect is a decrease in 1.25(OH) 2 vit D3 level which reduces Ca and P absorption from the intestine (14). Serum P level is sustained in the normal range until the phosphaturic effect of FGF23 is blunted due to the diminished number of nephrons with progressive CKD (18). FGF23 also has an inhibitory effect on PTH secretion, though given the potential for extremely high levels of PTH in endstage CKD the importance of this effect is not clear (17).…”

“…In patients with CKD, persistent stimulation of the parathyroid glands due to hyperphosphatemia, low 1.25 (OH) 2 vit D3 and intermittent hypocalcemia leads to diffuse (polyclonal) hyperplasia which transforms into nodular hyperplasia (monoclonal) (18). The glands develop nodular hyperplasia with several nodules in which parathyroid cells proliferate monoclonally with high growth potential, but express significantly less VDR and CaSR (20).…”