PTH—A Particularly Tricky Hormone

Garrett, Giorgia L.; Sardiwal, Sunita; Lamb, Edmund J.; Goldsmith, David

doi:10.2215/cjn.09580911

Cited by 90 publications

(81 citation statements)

References 89 publications

(65 reference statements)

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“…31 The importance of PTH as a biomarker of abnormal bone is controversial. 32,33 Cohort studies have shown an increased risk of fracture associated with low PTH 12,29,30 or very high PTH. 3,12,30,34 Some studies have found no significant relation to PTH.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

Moe

Abdalla

Chertow

et al. 2015

Journal of the American Society of Nephrology

178

116

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Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for #64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%. 26: 146626: -147526: , 201526: . doi: 10.1681 Patients with end stage renal disease (ESRD) on dialysis have increased risk of fractures compared with the general population. 1 Fracture incidence rates vary by geographic region, although rates are consistently higher in patients with CKD than matched controls from the same country. [2][3][4][5][6] Depending on the study, 10%-52% of patients receiving dialysis J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 99%

Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

Moe

Abdalla

Chertow

et al. 2015

Journal of the American Society of Nephrology

178

116

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“…The application of these newer analytical platforms to clinical cohorts is awaited, and independent validation is required. (32,33). Nonetheless, such experience with other mineral metabolism analytes should prompt attempts to harmonize FGF23 assay readout.…”

Section: Analytical Considerations Of Fgf23 Measurementmentioning

confidence: 99%

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Smith

2014

Clinical Journal of the American Society of Nephrology

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The emergence of fibroblast growth factor 23 as a potentially modifiable risk factor in CKD has led to growing interest in its measurement as a tool to assess patient risk and target therapy. This review discusses the analytical and clinical challenges faced in translating fibroblast growth factor 23 testing into routine practice. As for other bone mineral markers, agreement between commercial fibroblast growth factor 23 assays is poor, mainly because of differences in calibration, but also, these differences reflect the variable detection of hormone fragments. Direct comparison of readout from different assays is consequently limited and likely hampers setting uniform fibroblast growth factor 23-directed targets. Efforts are needed to standardize assay output to enhance clinical use. Fibroblast growth factor 23 is robustly associated with cardiovascular and renal outcomes in patients with CKD and adds value to risk assessments based on conventional risk factors. Compared with most other mineral markers, fibroblast growth factor 23 shows better intraindividual temporal stability, with minimal diurnal and week-to-week variability, but substantial interindividual variation, maximizing discriminative power for risk stratification. Conventional therapeutic interventions for the CKD-mineral bone disorder, such as dietary phosphate restriction and use of oral phosphate binders or calcimimetics, are associated with variable efficacy at modulating circulating fibroblast growth factor 23 concentrations, like they are for other mineral metabolites. Dual therapy with dietary phosphate restriction and noncalcium-based binder use achieves the most consistent fibroblast growth factor 23-lowering effect and seems best monitored using an intact assay. Additional studies are needed to evaluate whether strategies aimed at reducing levels or antagonizing its action have beneficial effects on clinical outcomes in CKD patients. Moreover, a better understanding of the mechanisms driving fibroblast growth factor 23 elevations in CKD is needed to inform the use of therapeutic interventions targeting fibroblast growth factor 23 excess. This evidence must be forthcoming to support the use of fibroblast growth factor 23 measurement and fibroblast growth factor 23-directed therapy in the clinic.

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“…Given the many other factors that influence clinical interpretation of PTH results (e.g., between-method differences, specificity) [48], laboratory professionals should ensure samples are appropriately stored. Based on the evidence reviewed here, the following recommendation seems appropriate:…”

Section: We Recommend Blood Samples For Pth Measurement Should Be Takmentioning

confidence: 99%

Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review

Hanon

Sturgeon

Lamb

2013

Clinical Chemistry and Laboratory Medicine (CCLM)

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Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential. We have undertaken a systematic review of these pre-analytical conditions. An electronic search of the PubMed, Embase, Cochrane, Centre for Research and Dissemination and Bandolier databases was undertaken. Of 5511 papers identified, 96 underwent full text review, of which 83 were finally included. At room temperature PTH was stable in ethylenediaminetetraacetic acid (EDTA) preserved whole blood for at least 24 h and in EDTA plasma for at least 48 h after venepuncture. Losses were observed in clotted blood samples after 3 h and in serum after 2 h. At 4°C PTH was more stable in EDTA plasma (at least 72 h) than serum (at least 24 h). Central venous PTH concentrations were higher than peripheral venous concentrations. In the northern hemisphere, PTH concentrations were higher in winter than summer. PTH has a circadian rhythm characterised by a nocturnal acrophase and mid-morning nadir. Data related to frozen storage of PTH (−20°C and −80°C) were limited and contradictory. We recommend that blood samples for PTH measurement should be taken into tubes containing EDTA, ideally between 10:00 and 16:00, and plasma separated within 24 h of venepuncture. Plasma samples should be stored at 4°C and analysed within 72 h of venepuncture. Particular regard must be paid to the venepuncture site when interpreting PTH concentration. Further research is required to clarify the suitability of freezing samples prior to PTH measurement.

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PTH—A Particularly Tricky Hormone

Cited by 90 publications

References 89 publications

Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis

The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review

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