Parathyroid hormone and its fragments in children with chronic renal failure

Waller, Simon; Reynolds, Anthony P.; Ridout, Deborah; Cantor, Tom; Gao, Ping; Rees, Lesley

doi:10.1007/s00467-003-1267-1

Cited by 16 publications

(20 citation statements)

References 37 publications

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“…These observations concur with earlier data in a similar population [6], and confirm the now well established relationship between newer more specific 1-84 PTH and iPTH assays [4,12,25,[26][27][28]. Whilst 1-84 PTH levels were correlated with calcium levels prior to dialysis this relationship was lost during dialysis.…”

Section: Discussionsupporting

confidence: 91%

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Effect of haemodialysis on markers of bone turnover in children

2007

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'Intact' parathyroid hormone (iPTH) assays are used to measure serum PTH levels in haemodialysis patients to diagnose and monitor secondary hyperparathyroidism and consequent renal osteodystrophy (ROD); these assays exhibit cross-reactivity with long carboxyl-terminal PTH fragments (C-PTH) that accumulate in end stage renal failure (ESRF) and antagonise the biological activity of the whole molecule, 1-84 PTH. The effects of haemodialysis on C-PTH are not known. We investigated how haemodialysis affects serum concentrations of calcium, iPTH, 1-84 PTH, C-PTH, and other markers of bone turnover; bone-specific alkaline phosphatase (BALP) and type 1 collagen cross-linked telopeptide (CTx). Fifteen patients, mean (range) age 13.9 (4.3-17.6) years, haemodialysed for a median of 16.3 (4-41) months, had pre- and post-dialysis serum samples collected for routine biochemistry, BALP, CTx, iPTH and 1-84 PTH assays. Changes to serum concentrations and relationships between these biochemical surrogate markers of ROD were investigated. Serum phosphate and PTH levels (measured by both assays) fell significantly during dialysis, whereas serum calcium, C-PTH, the 1-84 PTH: C-PTH ratio and BALP and CTx concentrations were not significantly changed. 1-84 PTH levels were related to pre but not post dialysis serum calcium levels and changes to 1-84 PTH levels during dialysis were related to changes in serum calcium levels. 1-84 PTH and iPTH were reduced by haemodialysis, whereas levels of BALP and CTx remained stable post-dialysis. The relationship between BALP and CTx and bone histology requires investigation to determine whether they are more useful markers of bone turnover in this patient group.

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Section: Discussionsupporting

confidence: 91%

“…The pre-dialysis median 1-84 PTH: C-PTH ratio was only 1.5, considerably lower (mean 3.3) than that of a normal population [28], reflecting the relative preponderance of C-PTH that accumulates in patients with end stage renal failure [29,30]. The effect of haemodialysis on the 1-84 PTH: C-PTH ratio was variable.…”

Section: Discussionmentioning

confidence: 98%

Effect of haemodialysis on markers of bone turnover in children

2007

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“…Serum PTH determinations with the 1 st PTH-IMA have been consistently higher than with the 2 nd PTH-IMA over a wide range of serum PTH concentrations in different laboratories. Thus, 1 st PTH-IMA may overestimate parathyroid gland function by 40%-50% [23,24,25,26,28,31,35,36]. In addition, similar degrees of correlation were obtained between both PTH assays and bone formation rates determined by double tetracycline labeling [27].…”

Section: Pth Determinations By 1 St and 2 Nd Pth-imas In Patients Witsupporting

confidence: 52%

“…Furthermore, Reichel et al [28] more recently demonstrated similar predictive values for the assessment of renal bone disease when using 1 st and 2 nd PTH-IMAs (from Scantibodies) in a large group of patients undergoing maintenance hemodialysis; however, no biopsies were performed in that study. In contrast, Waller et al [36] suggested that 2 nd PTH-IMA (Scantibodies) may be a more accurate predictor of renal osteodystrophy than 1 st PTH-IMA, but bone histomorphometry analysis was not performed.…”

Section: Pth Determinations By 1 St and 2 Nd Pth-imas In Patients Witmentioning

confidence: 88%

New PTH assays and renal osteodystrophy

Salusky

Jüppner

2004

Pediatric Nephrology

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Parathyroid hormone (PTH) levels have been used instead of bone histomorphometric analysis in renal failure, but the assessment of tetracycline-labeled bone biopsy remains the most reliable method to diagnose the different subtypes of renal osteodystrophy. The availability of the first-generation immunometric PTH assay (1(st) PTH-IMA) allowed the distinction between the different types of renal bone diseases. However, 1(st) PTH-IMA not only detects the intact hormone PTH(1-84), but also additional PTH truncated fragments. A second-generation immunometric PTH assay (2(nd) PTH-IMA) recognizes only PTH(1-84) and possible PTH fragments that are truncated at the carboxyl-terminus, but not PTH(7-84). In addition, whether assessment of the ratio PTH(1-84) and amino-terminally truncated PTH(1-84) fragments is a better predictor of bone turnover remains controversial. An initial study using the 2(nd) PTH-IMA suggested that the ratio between PTH(1-84) and amino-terminally truncated PTH(1-84) fragments more accurately predicts bone turnover in adult patients treated with hemodialysis. However, subsequent studies using the Scantibodies assay have failed to better predict the underlying bone disease in adults undergoing maintenance hemodialysis. Furthermore, a different 2(nd) PTH-IMA (Immutopics) with similar, but not identical, in vitro characteristics did not show a superior predictive value of the ratio in pediatric patients treated with peritoneal dialysis. Although the 2(nd) PTH-IMA may provide important new insights into the physiology of parathyroid gland function, at present, measurement of PTH using either 1(st) or 2(nd) PTH-IMAs provides similar accuracy for predicting bone turnover in patients treated with dialysis. Thus, the current data do not yet support the claim that 2(nd) PTH-IMAs provide an advantage over 1(st) PTH-IMAs for the diagnosis of the different subtypes of renal bone diseases.

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“…There were 156 conservatively managed children (CRF group), 49 with renal transplants (transplant group), 26 on peritoneal dialysis and 10 on haemodialysis (dialysis group). The epidemiology and PTH results of these children have been reported previously [7]. At clinic appointments (post peritoneal dialysis and pre haemodialysis) extra blood was taken for two PTH assays.…”

Section: Methodsmentioning

confidence: 99%

Differences between ?intact? PTH and 1?84 PTH assays in chronic renal failure and dialysis

Waller

Ridout

Cantor³

et al. 2004

Pediatr Nephrol

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"Intact" parathyroid hormone (iPTH) assays overestimate actual PTH as they cross-react with non (1-84) PTH fragments (C-PTH) that accumulate in renal failure. New assays that measure just 1-84 PTH (CAP-PTH) are now available. It has been suggested that there is a linear relationship between the two assays; however, increased C-PTH levels are found as glomerular filtration rate (GFR) declines and in patients on dialysis. We investigated the relationship between iPTH and CAP-PTH in children with chronic renal failure (CRF) managed conservatively and on dialysis. We investigated 241 children, 156 with a GFR <60 ml/min per 1.73 m(2) managed conservatively, 49 post renal transplant (and GFR <60 ml/min per 1.73 m(2)) and 36 on dialysis, by measuring PTH levels by iPTH and CAP-PTH assays. Multiple regression analysis comparing differences between PTH levels in each patient group was performed. Correlation slopes between iPTH and CAP-PTH assays differed between CRF and dialysis patients (P=0.001). These assays perform differently in CRF and dialysis patient groups. Studies investigating the correlation between newer assays and bone histology are required to determine whether these more-specific PTH assays are superior surrogate markers of bone turnover.

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Parathyroid hormone and its fragments in children with chronic renal failure

Cited by 16 publications

References 37 publications

Effect of haemodialysis on markers of bone turnover in children

Effect of haemodialysis on markers of bone turnover in children

New PTH assays and renal osteodystrophy

Differences between ?intact? PTH and 1?84 PTH assays in chronic renal failure and dialysis

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