Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease

Geng, Sinong; Kuang, Zhaobin; Peissig, Peggy L.; Page, David L.; Maursetter, Laura; Hansen, Kerstin

doi:10.1007/s00198-019-05033-3

Cited by 34 publications

(19 citation statements)

References 32 publications

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“… 7 , 20 A large prospective database including 5100 subjects with CKD stages 3–4 showed that PTH was an independent factor predictive of fractures, low PTH having a protective effect. 44 Moreover, the reduction of PTH by calcimimetics as in the EVOLVE (EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events) trial and using an unadjusted intention-to-treat analysis, showed that cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics of multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16% to 29%.…”

Section: Discussionmentioning

confidence: 99%

“…In hemodialysis patients, high PTH is associated with increased risk of fracture 17,18 , but this risk is also observed with very low PTH levels 7,20 . Large prospective database including 5,100 subjects with CKD stages [3][4] showed that PTH was an independent factor predictor of fractures, low PTH having a J o u r n a l P r e -p r o o f protective effect 44 . Moreover, the reduction of PTH by calcimimetics as in the EVOLVE (EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events) trial and using an unadjusted intention-to-treat analysis, showed that cinacalcet did not reduce the rate of clinical fracture.…”

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

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Longitudinal Bone Loss Occurs at the Radius in CKD

Cailleaux

Ostertag

Metzger

et al. 2021

Kidney International Reports

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Section: Discussionmentioning

confidence: 99%

Section: J O U R N a L P R E -P R O O Fmentioning

confidence: 99%

Longitudinal Bone Loss Occurs at the Radius in CKD

Cailleaux

Ostertag

Metzger

et al. 2021

Kidney International Reports

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“…With current guidelines no longer recommending the routine use of calcitriol and active vitamin D due to increased risk of hypercalcaemia, and now a growing body of evidence suggesting that the current targets for vitamin D repletion may not be generalisable to CKD (levels of 25(OH)D ≥ 50 ng/mL may be required to control PTH) [60,77], the optimal treatment strategies for patients with SHPT in non-dialysis CKD remain to be clearly defined. Nevertheless, the associations between elevated PTH levels and morbidity and mortality [2] indicate a need for effective management of SHPT without delaying treatment until these elevations become severe and progressive in CKD stage G4-5 and at which point the benefits of using calcitriol/active vitamin D may be more balanced against the risks of hypercalcaemia [7].…”

Section: How Do We Choose a Therapeutic Option For Shpt In Non-dialysis Ckd?mentioning

confidence: 99%

“…A review of the pathogenesis of SHPT in CKD is beyond the scope of this article, and the reader is referred to review articles on this subject (e.g., Cunningham, 2011) [6]. 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 such, approaches to manage SHPT have formed an important focus of treatment in CKD.…”

Section: Introductionmentioning

confidence: 99%

“…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 ]. In 2017, CKD was estimated to affect 9.1% of the global population; however, only a minority had advanced renal dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Where are we now? Emerging opportunities and challenges in the management of secondary hyperparathyroidism in patients with non-dialysis chronic kidney disease

Ketteler

Ambühl

2021

J Nephrol

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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

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Vitamin D Analogues and Fracture Risk in Chronic Kidney Disease: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

2022

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Vitamin D receptor agonists (VDRAs) are commonly prescribed in chronic kidney disease (CKD). However, their protective effects on bone remain controversial. We performed a systematic review and meta‐analysis of randomized controlled trials (RCTs) to evaluate the effect of VDRAs on fracture risk and bone mineral density (BMD) in adult patients with CKD. We searched MEDLINE, EMBASE, CENTRAL, http://clinicaltrials.gov, and the WHO's International Clinical Trials Registry Platform databases from inception to June 19, 2021. We included RCTs comparing VDRAs, to placebo or another medication, in adults with CKD requiring or not dialysis. Conference abstracts and trials involving kidney transplant recipients and/or comparing VDRAs to antiresorptive or anabolic bone therapy were excluded. Primary outcome was fracture at any anatomical site. Secondary outcomes were BMD at femoral neck, lumbar spine, and/or total hip. Prespecified subgroup analyses were conducted according to baseline demographics, overall risk of bias, and follow‐up time. From 6868 references retrieved, eight RCTs were eligible: five reported fracture, two reported BMD, and one reported both outcomes. As comparator, one study used no VDRAs, one used nutritional intervention and no medication, and six used placebo. In meta‐analysis, VDRAs were not associated with a significant reduction in total fractures in overall (risk ratio = 0.79, 95% confidence interval 0.38–1.65, I2 = 0%, six trials, 1507 participants, 27 fractures) or in prespecified subgroup analyses. Three trials reported BMD at different sites and with different BMD measurements; thus, a meta‐analysis could not be performed. Two RCTs were at high risk of bias, notably because of deviations from the intended interventions. As limitation, we have to mention the low total number of fractures included in our meta‐analysis. In conclusion, current evidence from RCTs is insufficient to associate VDRAs with bone protection in CKD. Further large and long‐term studies specifically designed to evaluate the efficacy of VDRAs on bone outcomes are thus required. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

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Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease

Cited by 34 publications

References 32 publications

Longitudinal Bone Loss Occurs at the Radius in CKD

Longitudinal Bone Loss Occurs at the Radius in CKD

Where are we now? Emerging opportunities and challenges in the management of secondary hyperparathyroidism in patients with non-dialysis chronic kidney disease

Vitamin D Analogues and Fracture Risk in Chronic Kidney Disease: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

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