Abstract
Rising levels of parathyroid hormone (PTH) are common in patients with chronic kidney disease (CKD) not on dialysis and are associated with an elevated risk of morbidity (including progression to dialysis) and mortality. However, there are several challenges for the clinical management of secondary hyperparathyroidism (SHPT) in this population. While no recognised target level for PTH currently exists, it is accepted that patients with non-dialysis CKD should receive early and regular monitoring of PTH from CKD stage G3a. However, studies indicate that adherence to monitoring recommendations in non-dialysis CKD may be suboptimal. SHPT is linked to vitamin D [25(OH)D] insufficiency in non-dialysis CKD, and correction of low 25(OH)D levels is a recognised management approach. A second challenge is that target 25(OH)D levels are unclear in this population, with recent evidence suggesting that the level of 25(OH)D above which suppression of PTH progressively diminishes may be considerably higher than that recommended for the general population. Few therapeutic agents are licensed for use in non-dialysis CKD patients with SHPT and optimal management remains controversial. Novel approaches include the development of calcifediol in an extended-release formulation, which has been shown to increase 25(OH)D gradually and provide a physiologically-regulated increase in 1,25(OH)2D that can reliably lower PTH in CKD stage G3–G4 without clinically meaningful increases in serum calcium and phosphate levels. Additional studies would be beneficial to assess the comparative effects of available treatments, and to more clearly elucidate the overall benefits of lowering PTH in non-dialysis CKD, particularly in terms of hard clinical outcomes.Graphic abstract
Highlights
Chronic kidney disease (CKD) is a major and growing global public health burden that is associated with significant morbidity and has continued to rise in rank among the leading causes of death over the last 3 decades [1]
Recent studies demonstrate that secondary hyperparathyroidism (SHPT) is associated with the risk of cardiovascular events regardless of CKD stage [11], and in patients with non-dialysis CKD, parathyroid hormone (PTH) is a predictor of risk of fractures, vascular events, progression to dialysis and death [2, 15]
The known pathophysiology, together with recent data, illustrate the rationale for treatment of SHPT and vitamin D insufficiency/deficiency in non-dialysis CKD, and the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the management of CKD-mineral and bone disorder recommend that patients with CKD stage G3–G4 and progressively rising or persistently elevated PTH levels above the upper limit of normal should be evaluated for vitamin D deficiency as one of the modifiable risk factors [7]
Summary
Chronic kidney disease (CKD) is a major and growing global public health burden that is associated with significant morbidity and has continued to rise in rank among the leading causes of death over the last 3 decades [1]. Progression of CKD is associated with increasing risk of death, cardiovascular events, and hospitalisation [2, 3]. The characteristic mineral metabolism disturbances and rising PTH levels of SHPT independently predict risk of fractures, vascular events, progression to dialysis and death [2, 3, 10, 11]. As reflected in recent guidelines, studies have called into question the routine use of calcitriol and active vitamin D analogues for the management of SHPT in CKD stage G3a–G5 due to increased risk of hypercalcaemia [7]. Recent studies demonstrate that SHPT is associated with the risk of cardiovascular events regardless of CKD stage [11], and in patients with non-dialysis CKD, PTH is a predictor of risk of fractures, vascular events, progression to dialysis and death [2, 15]. A recent multicentre prospective cohort study from the Fukuoka Kidney Disease Registry (3,384 non-dialysis CKD patients) explored the relationship between PTH concentrations and the prevalence of atrial fibrillation.
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