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Parathyroid hormone and growth in children with chronic renal failure
Simon C Waller1, Deborah Ridout, Tom Cantor
1Nephro-Urology Unit, Insitute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom. swaller@doctors.org.uk
Insights
Normal parathyroid hormone (PTH) levels are suitable for children with chronic renal failure (CRF), supporting normal growth. However, the ratio of 1-84 PTH to C-PTH may be clinically significant in managing these patients.
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Metabolic Bone Disease
Background:
- Optimal parathyroid hormone (PTH) targets for pediatric chronic renal failure (CRF) are unknown, impacting bone health and growth.
- Existing "intact" PTH (iPTH) assays have limitations due to cross-reactivity with C-terminal PTH fragments (C-PTH).
- C-PTH fragments can antagonize the biological activity of 1-84 PTH, complicating interpretation of PTH levels.
Purpose of the Study:
- To investigate the relationship between PTH levels, the 1-84 PTH:C-PTH ratio, and growth rate in children with CRF.
- To assess the clinical significance of C-PTH fragments in pediatric CRF.
- To determine appropriate PTH concentrations for optimizing growth and minimizing renal osteodystrophy.
Main Methods:
- Study included 162 pediatric patients with CRF (conservatively managed, transplanted, and dialysis patients).
- Patients were monitored over a median of 1.1 years, with regular clinic visits for measurements.
- Measurements included intact PTH (iPTH), cyclase-activating PTH (CAP-PTH), and height to calculate height standard deviation score (DeltaHtSDS).
Main Results:
- Mean PTH levels were generally within normal ranges for conservatively managed CRF patients.
- Dialysis patients exhibited higher CAP-PTH and iPTH levels compared to normal ranges.
- No significant relationship was found between PTH concentrations and growth rate (DeltaHtSDS) in most groups.
- A lower 1-84 PTH:C-PTH ratio was observed in dialyzed patients, with worsening renal function, and with abnormal PTH levels.
- A weak positive correlation was found between the 1-84 PTH:C-PTH ratio and DeltaHtSDS (r=0.2, P=0.01).
Conclusions:
- Normal PTH concentrations appear appropriate for children with CRF managed conservatively, supporting normal growth.
- The ratio of 1-84 PTH to C-PTH may hold clinical significance in pediatric CRF.
- Further research into the role of C-PTH fragments is warranted.
Background:
In pediatric chronic renal failure (CRF) optimal parathyroid hormone (PTH) concentrations that minimize renal osteodystrophy and maximize growth are unknown. The search for optimum concentrations has been complicated as currently used "intact" PTH (iPTH) assays cross-react with long carboxyl-terminal PTH fragments (C-PTH), which antagonize the biologic actions of 1-84 PTH. The purpose of this study was to investigate the relationship between PTH, the 1-84 PTH:C-PTH ratio and growth rate in children with CRF.
Methods:
A total of 162 patients, median (range) age 9.9 years (0.3 to 17.1 years), were recruited: 136 with a glomerular filtration rate (GFR) <60 mL/min/1.73 m(2)[96 managed conservatively (CRF group) and 40 transplanted patients], and 26 dialysis patients. Over a median (range) period of 1.1 years (0.5 to 1.7 years), children attended five (three to 15) clinics at which iPTH, cyclase-activating PTH (CAP-PTH), and height were measured.
Results:
Mean PTH concentrations were within the normal range for both assays for the CRF group and up to twice the upper limit of normal for the dialysis group; CAP-PTH 24.8 pg/mL and 59.9 pg/mL (normal range 5 to 39 pg/mL), iPTH 37.1 pg/mL, and 102.6 pg/mL, respectively (normal range 14 to 66 pg/mL). The patients grew normally (change in height standard deviation score per year (DeltaHtSDS) =-0.01). There was no relationship between PTH concentrations and DeltaHtSDS in any patient group. The 1-84 PTH:C-PTH ratio was lower in dialyzed patients (P= 0.003), with worsening renal function (P= 0.047) and with PTH concentrations outside the normal range (P= 0.01). There was a weak correlation between the 1-84 PTH:C-PTH ratio and the DeltaHtSDS (r= 0.2, P= 0.01).
Conclusion:
Normal range PTH concentrations are appropriate, allowing normal growth in children with CRF managed conservatively. C-PTH may be of clinical significance.
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