Secondary Hyperparathyroidism
The Role of Vitamin D for the Prevention and Treatment of Secondary Hyperparathyroidism in Dialysis Patients
Guillaume Jean, MD and Charles Chazot, MD Centre de Rein Artificiel, NEPHROCARE, Tassin le Demi-Lune
Abstract
The effects of secondary hyperparathyroidism (SHPT) on mineral metabolism, bones, and the cardiovascular system in chronic kidney disease (CKD) patients should lead to the development of an efficient strategy for prevention and treatment of SHPT; however, this strategy remains controversial. Until recent years, only calcitriol analogs (CAs) were recommended for SHPT treatment in patients with CKD. Nonetheless, in dialysis patients, native vitamin D derivatives (NVDs) are able to increase calcitriol production and to decrease parathyroid hormone (PTH) levels without significant hypercalcemia or hyperphosphatemia. Some new data on the non-osseous effects of NVDs provide evidence for NVD supplementation in patients with CKD, who frequently present with vitamin D deficiency. The new recommendation for treatment of vitamin D deficiency and the introduction of calcimimetics provide the opportunity to develop a consensual strategy based largely on the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Concurrently with the control of hyperphosphatemia, vitamin D supplementation appears to be a cheap and safe first-line therapy for SHPT. Notwithstanding, patients with persistently high levels of PTH could be administered CAs and calcimimetic drugs, depending on their serum levels of calcium and phosphorus. However, further studies are mandatory to compare the outcomes for CKD patients using NVDs, CAs, or both, with different serum PTH levels.
Keywords Hyperparathyroidism, vitamin D, calcitriol analogs, mineral metabolism, survival, dialysis, chronic kidney disease
Disclosure: The authors both serve as consultants for Fresenius Medical Care. Received: March 23, 2011 Accepted: May 12, 2011 Citation: US Nephrology, 2011;6(1):29–34 Correspondence: Guillaume Jean, MD, Centre de Rein Artificiel, 42 avenue du 8 mai 1945, 69160 Tassin la Demi-Lune, France. E:
guillaume-jean-crat@wanadoo.fr
Secondary hyperparathyroidism (SHPT) is frequently observed in patients with chronic kidney disease (CKD).1
The underlying
pathophysiology is relatively well understood, but the management of SHPT remains a challenge owing to the complex relationship between hormones, bones, mineral metabolism, and therapies. An understanding of the effects of SHPT on mineral metabolism, bones, and cardiovascular disease could lead to improvements in its prevention and treatment.
The Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommended using vitamin D receptor (VDR) agonist for lowering the elevated parathyroid hormone (PTH) levels.2
The term VDR agonist
excludes native vitamin D derivates (NVDs) that were not recommended for patients with CKD stage 5. To clearly separate VDR agonists from native compounds, we chose to identify the former, referring to them as ‘calcitriol analogs’ (CAs). CAs may also increase serum calcium and phosphate, and this effect is potentially harmful.3 This has led to the introduction of compounds with less calcemic and phosphatemic side effects.4
The guidelines were recently updated by the members of the Kidney Disease: Improving Global Outcomes (KDIGO) projects.1
© TOUCH BRIEFINGS 2011 The major
novelties were the new PTH target (two to nine times the upper limit of the assay), recommendation of alkaline phosphatase (ALP) as a bone marker, probable usefulness of NVD supplementation, and introduction of calcimimetic drugs in the strategy for SHPT management.
Vitamin D deficiency is frequently observed in CKD patients.5 associated with high mortality,6,7 and kidney disease progression.9
It has been
vascular calcification and stiffness,8 Some observational studies showed
that NDV supplementation, besides restoring the levels of both 25-hydroxyvitamin D (25-D) and 1,25-dihydroxyvitamin D (1,25-D), could help to lower PTH levels without side effects and at a reduced cost.10
However, only CAs have been studied and associated with a good survival rate in large observational studies of hemodialysis (HD) patients.11,12
Recent studies, such as the Open-label, randomized study using cinacalcet to improve achievement of kidney disease outcomes quality initiative targets in patients with end-stage renal disease (OPTIMA),13 the Randomized study to evaluate the effects of cinacalcet plus low dose vitamin D on vascular calcification in subjects with chronic kidney disease receiving hemodialysis (ADVANCE),14
and the Evaluation of cinacalcet HCl therapy to lower cardiovascular events (EVOLVE) study15 29
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