An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism

Hh, Malluche; Mc, Monier-Faugere; Wang, G; Jm, Frazã O; Charytan, Chaim; Jw, Coburn; Dw, Coyne; Mr, Kaplan; Baker, Nigel; Lc, McCary; Sa, Tongmin; Wg, Goodman

doi:10.5414/cnp69269

Cited by 108 publications

(72 citation statements)

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“…The combined results of RCTs and phase 4 studies confirmed these results (11,13,21,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)) (Table1), among other benefits, including a substantial reduction of the elevated bone formation rate/tissue area, generally improving bone disease (57,58). Importantly, two recent prospective RCTs evaluated both the efficacy of cinacalcet in preventing the progression of CV calcifications (ADVANCE) (11), and its effect on clinical outcomes, including all-cause mortality and CV events (EVOLVE) (13).…”

Section: Cinacalcet Use In Patients With Ckd Treated By Dialysissupporting

confidence: 66%

“…Studies have found that approximately 19% of patients may show levels of intact PTH below the classic 150 pg/ml target (53,85), and cases of ABD have been confirmed after cinacalcet treatment and chronic low PTH levels (57,58). Low as well as high PTH levels have been associated with decreased survival in dialysis patients; consequently, both "extremes of risk" should be avoided.…”

Section: Pth Oversuppressionmentioning

confidence: 99%

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Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Bover

Ureña

Ruiz-García

et al. 2016

Clinical Journal of the American Society of Nephrology

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CKD and CKD-related mineral and bone disorders (CKD-MBDs) are associated with high cardiovascular and mortality risks. In randomized clinical trials (RCTs), no single drug intervention has been shown to reduce the high mortality risk in dialysis patients, but several robust secondary analyses point toward important potential beneficial effects of controlling CKD-MBD-related factors and secondary hyperparathyroidism. The advent of cinacalcet, which has a unique mode of action at the calcium-sensing receptor, represented an important step forward in controlling CKD-MBD. In addition, new RCTs have conclusively shown that cinacalcet improves achievement of target levels for all of the metabolic abnormalities associated with CKD-MBD and may also attenuate the progression of vascular and valvular calcifications in dialysis patients. However, a final conclusion on the effect of cinacalcet on hard outcomes remains elusive. Tolerance of cinacalcet is limited by frequent secondary side effects such as nausea, vomiting, hypocalcemia and oversuppression of parathyroid hormone, which may cause some management difficulties, especially for those lacking experience with the drug. Against this background, this review aims to summarize the results of studies on cinacalcet, up to and including the publication of the recent ADVANCE and EVOLVE RCTs, as well as recent post hoc analyses, and to offer practical guidance on how to improve the clinical management of the most frequent adverse events associated with cinacalcet, based on both currently available information and personal experience. In addition, attention is drawn to less common secondary effects of cinacalcet treatment and advisable precautions.

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Section: Cinacalcet Use In Patients With Ckd Treated By Dialysissupporting

confidence: 66%

Section: Pth Oversuppressionmentioning

confidence: 99%

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Bover

Ureña

Ruiz-García

et al. 2016

Clinical Journal of the American Society of Nephrology

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“…Independent variables for inclusion were selected using a backward stepwise algorithm with P Յ 0.20 to enter the model and P Յ 0.05 to remain in the model. The classification of "low," "normal," and "high" bone turnover was based on our normative database (27)(28)(29). The outcome group "low" bone turnover was defined as Ac.f.…”

Section: Statistical Analysesmentioning

confidence: 99%

Sclerostin and Dickkopf-1 in Renal Osteodystrophy

Cejka¹,

Herberth²,

Branscum³

et al. 2011

Clinical Journal of the American Society of Nephrology

225

176

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SummaryBackground and objectives The serum proteins sclerostin and Dickkopf-1 (Dkk-1) are soluble inhibitors of canonical wnt signaling and were recently identified as components of parathyroid hormone (PTH) signal transduction. This study investigated the associations between sclerostin and Dkk-1 with histomorphometric parameters of bone turnover, mineralization, and volume in stage 5 chronic kidney disease patients on dialysis (CKD-5D). Design, setting, participants, & measurementsIn a cross-sectional study, 60 CKD-5D patients underwent bone biopsies followed by histomorphometry. Levels of sclerostin, Dkk-1, and intact PTH (iPTH) were determined in blood.Results Serum levels of sclerostin and iPTH correlated negatively. In unadjusted analyses, sclerostin correlated negatively with histomorphometric parameters of turnover, osteoblastic number, and function. In adjusted analyses, sclerostin remained a strong predictor of parameters of bone turnover and osteoblast number. An observed correlation between sclerostin and cancellous bone volume was lost in regression analyses. Sclerostin was superior to iPTH for the positive prediction of high bone turnover and number of osteoblasts. In contrast, iPTH was superior to sclerostin for the negative prediction for high bone turnover and had similar predictive values than sclerostin for the number of osteoblasts. Serum levels of Dkk-1 did not correlate with iPTH or with any histomorphometric parameter.Conclusions Our data describe a promising role for serum measurements of sclerostin in addition to iPTH in the diagnosis of high bone turnover in CKD-5D patients, whereas measurements of Dkk-1 do not seem to be useful for this purpose.

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“…We conducted a prospective, double-blind, placebo-controlled trial to assess the effect of cinacalcet on bone histology and serum markers of bone metabolism in dialysis patients with ROD (32). Patients with intact PTH Ն300 pg/ml were selected to be assigned 2 to 1 to receive cinacalcet or placebo with concurrent vitamin D and/or phosphate binder therapy.…”

Section: Effects Of the Calcimimetic Cinacalcet Hcl On Renal Osteodysmentioning

confidence: 99%

Effects of Treatment of Renal Osteodystrophy on Bone Histology

Malluche¹,

Mawad²,

Monier‐Faugere³

2008

Clinical Journal of the American Society of Nephrology

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Renal osteodystrophy is characterized by abnormalities in bone turnover, mineralization, and bone volume. The effects of treatment modalities for renal osteodystrophy on bone should be analyzed with respect to these abnormalities. The major treatment modalities for renal osteodystrophy include phosphate binders, vitamin D compounds, and calcimimetics. Aluminum-containing phosphate binders have been shown to be toxic to bone secondary to their effects on bone turnover, mineralization, and bone volume. The use of calcium-based phosphate binders has been associated with the development of adynamic bone disease (low bone turnover), bone loss, and worsening of vascular calcifications. New nonaluminum, noncalcium phosphate binders have been developed (sevelamer hydrochloride and lanthanum carbonate). These agents show a potential for improvement in bone turnover and bone volume. Patients with renal osteodystrophy are deficient in calcitriol and often in calcidiol. Calcidiol deficiency has been underappreciated and deserves to be addressed in the treatment of patients with renal osteodystrophy. Calcitriol replacement therapy by daily oral administration is associated with frequent episodes of hypercalcemia and suppression of bone turnover in patients with stages 3 to 5 chronic kidney disease. Pulse oral or intravenous calcitriol administration induces frequent episodes of hypercalcemia or hyperphosphatemia, respectively, and achieves the same degree of correction of bone abnormalities. There are no data on the effects of paricalcitol or doxercalciferol on human bone. Experimental data, however, show that these two analogues and maxacalcitol may control serum parathyroid hormone levels without suppressing bone turnover. Calcimimetics lower parathyroid hormone levels and bone turnover.Clin J Am Soc Nephrol 3: S157-S163, 2008. doi: 10.2215/CJN.02500607 R enal osteodystrophy (ROD) starts early with loss of kidney function (approximately 50% loss of glomerular infiltration rates [1]). Virtually all patients with advanced chronic kidney disease (CKD) have ROD, and an association between histologic changes in bone turnover and vascular calcifications has been described (2,3). This association underlines the importance of treatment of ROD. The main abnormalities of ROD encompass changes in turnover, mineralization, and bone volume (4,5); therefore, effects of treatment modalities should be analyzed with respect to these three abnormalities. Three major therapeutic groups are available for the management of ROD: phosphate binders (P-binders), vitamin D or vitamin D analogues, and calcimimetics. P-BindersUse of P-binders has evolved in the past 30 yr (6,7). Initially, aluminum-containing P-binders were used during the 1970s to 1980s. They were replaced by calcium-based P-binders in the 1980s because of toxicities associated with aluminum. In the early 1990s, non-calcium-based P-binders were introduced because, again, toxicities were found with high doses of calciumbased binders (2,8 -10). Most recently, new calcium-and aluminum-...

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An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism

Cited by 108 publications

References 0 publications

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Clinical and Practical Use of Calcimimetics in Dialysis Patients With Secondary Hyperparathyroidism

Sclerostin and Dickkopf-1 in Renal Osteodystrophy

Effects of Treatment of Renal Osteodystrophy on Bone Histology

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