Waller, Simon Charles; (2004) What is the optimal range for parathyroid hormone levels that maximise growth and minimise renal osteodystrophy in children with chronic renal failure? Doctoral thesis (M.D), UCL (University College London).

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Abstract

Background: Chronic Renal Failure (CRF) is associated with poor growth; renal osteodystrophy is one aetiology. Parathyroid Hormone (PTH) is the major circulating factor affecting bone turnover. Clinicians therapeutically manipulate PTH levels, however, optimum levels are undetermined. Aims: To investigate relationships between PTH, long carboxyl-terminal PTH fragments (C- PTH), growth, bone mineral density (BMD) and bone histology in children with CRF. Methods: 1. Case-note analysis; investigating relationship between growth and PTH. 2. Prospective study following children with varying degrees of CRF; investigating relationship between PTH levels, PTH/C-PTH ratio, growth and BMD. 3. Bone biopsy study; investigating relationship between bone histology, growth, BMD and surrogate markers of bone turnover. Results: 1. Ninety-nine case-notes were analysed. Median inclusion age 1.6 years, median GFR 22mls/min/1.73m²; data collected for 3.6 years. Median PTH was equal to upper limit of normal range (NR). Significant gains in height standard deviation score (Ht-SDS) were achieved, +0.09 per year. 2. One-hundred-ninety-four children, 127 with a GFR<60, 26 on dialysis and 41 transplanted patients with a GFR<60, were followed for a mean 1.1 years. Good growth with no change to Ht-SDS was demonstrated. Growth was best with NR PTH levels and with higher PTH/C-PTH ratio. This ratio decreased with worsening CRF, in dialysed patients and with PTH levels outside NR. 3. Fifteen patients had bone biopsies at transplantation or dialysis catheter insertion. All had abnormal bone histology. PTH and bone specific alkaline-phosphatase levels correlated and both also correlated with bone turnover. Conclusion: In children with CRF calcium, phosphate and PTH can be maintained within the NR using dietary phosphate restriction, calcium based phosphate binders and small doses of alfacalcidol. Children with NR PTH levels maintain good growth and normal BMD. Nevertheless by the time they reach end-stage renal failure they are likely to have renal osteodystrophy.

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