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In children with chronic renal failure at risk of bone disease, which interventions prevent or treat the condition?
Studies were selected which compared any active intervention with any other or placebo in the treatment of children with renal failure to prevent bone disease.
Cochrane Renal Group's specialised register, CCTR, MEDLINE, EMBASE, reference lists and abstracts were searched without language restriction. The quality of the studies was assessed by the Cochrane ‘risk of bias’ criteria. Fifteen studies were included.
The 15 studies included 369 patients, and undertook five different comparisons. Two of these (ergosterols and phosphate binders) are no longer used in clinical practice. The quality of the included studies varied, with most items showing low risk of bias in only one third of the included trials. Meta-analysis demonstrated that treatment with vitamin D preparations improved biochemical surrogates of bone turnover, and did not demonstrate differences between routes of administration or doses. Phosphate binders were effective in reducing serum phosphate. In very few instances were direct patient-relevant outcomes reported.
The use of vitamin D analogues is effective in reducing parathyroid hormone (PTH) but has uncertain effects on direct patient-relevant outcomes of bone health. Further research is needed to determine optimum doses and scheduling.
In children with impaired renal function it is widely believed that controlling phosphate and PTH levels will treat or prevent ‘renal rickets’. The standard approach has been to lower phosphate first by dietary interventions, then if necessary by the addition of phosphate binders. The use of vitamin D preparations helps increase plasma calcium and reduce PTH.
Geary, Hodson and Craig's detailed review concludes that vitamin D preparations reduce PTH levels and that phosphate binders reduce plasma phosphate. They report that one particular phosphate binder (Sevelamer) causes fewer episodes of hypercalcaemia than others. The current body of evidence does not allow accurate assessment of clinical patient benefits to be inferred from the reduction in PTH. It is not known, but is believed, that by intervening we reduce fracture rates and bony deformities and improve growth.
Beyond the uncertainty of benefit, concern has been raised regarding a possible link between raised calcium/phosphate product and vascular calcification, with subsequent premature cardiovascular morbidity. Calcium absorption is increased by the vitamin D, but if diet and the binders do not control the high phosphate this results in a raised calcium phosphate product.
The clinical management of bone disease in children with renal impairment is more complex than just balancing two groups of medications. Children and their families need extensive dietary support in combination with their medication. In common with other chronic medical conditions, adherence with treatment is probably the single biggest issue in long-term management. In line with this the input of play specialists, teachers, psychologists, nurses and dieticians is vital.
The current goal in managing ‘renal bone disease’ is to attain levels of calcium and phosphate within the normal range in conjunction with a PTH within or close to the normal range. To accomplish all this with scanty evidence while doing no long-term harm is the challenge we currently face.
In common with the final statements of most Cochrane reviews, more evidence is needed. The evidence needed for clinicians is that which relates clinical outcomes to the surrogates of biochemical tests and markers of adherence. The creation of the Medicines for Children Research Network in the UK has seen a rise in the number of trials in children, and there is optimism that this may see the quality and quantity of published evidence in this area improve.
Source(s) of funding None.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.
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