The Case for Routine Parathyroid Hormone Monitoring

Sprague, Stuart M.; Moe, Sharon M.

doi:10.2215/cjn.04650512

Cited by 32 publications

(23 citation statements)

References 50 publications

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“…In this context, it must also be emphasized that PTH exerts actions on many tissues other than bone and that this study does not negate the usefulness of monitoring PTH levels in dialysis patients. 35 statistical analysis: SMS, HD; supervision or mentorship: SMS, EB-F, TBD, SMM. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis

Sprague

Bellorín-Font

Jorgetti

et al. 2016

American Journal of Kidney Diseases

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234

198

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Background: The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial.Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (220 C) serum.Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP).Reference Test: Bone histomorphometric assessment of turnover (bone formation rate/bone surface [BFR/ BS]) and receiver operating characteristic curves for discriminating diagnostic ability.Results: The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve . 0.70 but , 0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was ,103.8 pg/mL, and to discriminate high from nonhigh BFR/BS was .323.0 pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was ,33.1 U/L, and for high from nonhigh BFR/BS, 42.1 U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively.Limitations: Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries.Conclusions: The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions. Am J Kidney Dis. 67(4):559-566. ª 2016 by the National Kidney Foundation, Inc.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis

Sprague

Bellorín-Font

Jorgetti

et al. 2016

American Journal of Kidney Diseases

Self Cite

234

198

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“…Since PTH concentrations are clearly associated with mortality in patients suffering from chronic renal failure and since the PTH concentrations are at least partially changeable in response to alterations of the key regulators or drugs that influence the key regulators, national as well as international academic nephrology societies have established guidelines for target PTH concentrations in order to keep the patient in the “valley of survival” within the U-shaped PTH mortality curve. Such guidelines were, for example, established by the Kidney Disease Improving Global Outcomes (KDIGO) initiative and recommend repeated measurements in daily practice to monitor absolute concentrations and trends of changes of PTH [5]. However, PTH is a particularly tricky hormone to measure as stated in a very recent editorial [6].…”

Section: Introductionmentioning

confidence: 99%

Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

Hocher

Oberthür

Slowinski

et al. 2013

Kidney Blood Press Res

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Background: The biological properties of oxidized and non-oxidized PTH are substantially different. Oxidized PTH (oxPTH) loses its PTH receptor-stimulating properties, whereas non-oxidized PTH (n-oxPTH) is a full agonist of the receptor. This was described in more than 20 well published studies in the 1970^s and 80^s. However, PTH oxidation has been ignored during the development of PTH assays for clinical use so far. Even the nowadays used third generation assay systems do not consider oxidation of PTH We recently developed an assay to differentiate between oxPTH and n-oxPTH. In the current study we established normal values for this assay system. Furthermore, we compare the ratio of oxPTH to n-oxPTH in different population with chronic renal failure: 620 children with renal failure stage 2-4 of the 4C study, 342 adult patients on dialysis, and 602 kidney transplant recipients. In addition, we performed modeling of the interaction of either oxPTH or n-oxPTH with the PTH receptor using biophysical structure approaches. Results: The children had the highest mean as well as maximum n-oxPTH concentrations as compared to adult patients (both patients on dialysis as well as kidney transplant recipients). The relationship between oxPTH and n-oxPTH of individual patients varied substantially in all three populations with renal impairment. The analysis of n-oxPTH in 89 healthy control subjects revealed that n-oxPTH concentrations in patient with renal failure were higher as compared to healthy adult controls (2.25-fold in children with renal failure, 1.53-fold in adult patients on dialysis, and 1.56-fold in kidney transplant recipients, respectively). Computer assisted biophysical structure modeling demonstrated, however, minor sterical- and/or electrostatic changes in oxPTH and n-oxPTH. This indicated that PTH oxidation may induce refolding of PTH and hence alters PTH-PTH receptor interaction via oxidation induced three-dimensional structure alteration of PTH. Conclusion: A huge proportion of circulating PTH measured by current state-of-the-art assay systems is oxidized and thus not biologically active. The relationship between oxPTH and n-oxPTH of individual patients varied substantially. Non-oxidized PTH concentrations are 1.5 - 2.25 fold higher in patients with renal failure as compared to health controls. Measurements of n-oxPTH may reflect the hormone status more precise. The iPTH measures describes most likely oxidative stress in patients with renal failure rather than the PTH hormone status. This, however, needs to be demonstrated in further clinical studies.

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“…It must be emphasized that a significant proportion of patients with such intermediate PTH levels present quite different rates of bone remodeling, ranging from adynamic to normal to high turnover bone disease (25). Therefore, the clinical use of PTH (PTH monitoring and goals) is controversial (86,87). Nevertheless, because maintenance of appropriate PTH levels remains one of the main goals in contemporary nephrology practice, it probably should be monitored not only on a regular basis but also more frequently, at least until more specific new biomarkers and/or drugs with different targets demonstrate clinical superiority over current standard nephrology protocols (4,30).…”

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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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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The Case for Routine Parathyroid Hormone Monitoring

Cited by 32 publications

References 50 publications

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis

Diagnostic Accuracy of Bone Turnover Markers and Bone Histology in Patients With CKD Treated by Dialysis

Modeling of Oxidized PTH (oxPTH) and Non-oxidized PTH (n-oxPTH) Receptor Binding and Relationship of Oxidized to Non-Oxidized PTH in Children with Chronic Renal Failure, Adult Patients on Hemodialysis and Kidney Transplant Recipients

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

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