This review aimed to examine the benefits (improved growth rates, reduced risk of
bone fractures and
deformities, reduction in PTH levels) and harms (hypercalcaemia, blood vessel calcification, deterioration in kidney function) of interventions (including
vitamin D preparations and
phosphate binders) for the prevention and treatment of
metabolic bone disease in children with CKD.
SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 8 September 2015 through contact with the Trial's Search Co-ordinator using search terms relevant for this review.
SELECTION CRITERIA: Data were assessed for study eligibility, risk of bias and extracted independently by two authors. Results were reported as risk ratios (RR) or risk differences (RD) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) was used. Statistical analyses were performed using the random-effects model.
MAIN RESULTS: This review included 18 studies (576 children); three new studies were added for this update. Adequate sequence generation and allocation concealment were reported in 12 and 11 studies respectively. Only four studies reported blinding of children, investigators or outcome assessors. Nine studies were at low risk of attrition bias and 12 studies were at low risk of selective reporting bias.Eight different interventions were compared. Two studies compared intraperitoneal (IP) with oral
calcitriol. PTH levels were significantly lower with IP compared with oral
calcitriol (1 study: MD -501.00 pg/mL, 95% CI -721.54 to -280.46) but the number of children with abnormal bone histology did not differ between treatments. Three studies compared intermittent with daily oral
calcitriol. The change in mean height SDS (1 study: MD 0.13, 95% CI -0.22 to 0.48) and the percentage fall in
parathyroid hormone (PTH) levels at eight weeks (1 study: MD -5.50%, 95% CI -32.37 to 21.37) and 12 months (1 study: MD -6.00% 95% CI -25.27 to 13.27) did not differ between treatments.Four studies compared active
vitamin D preparations (
calcitriol,
paricalcitol, 1α-hydroxyvitamin D) with placebo or no specific treatment. One study reported
vitamin D preparations significantly reduced PTH levels (-55.00 pmol/L, 95% CI -83.03 to -26.97). There was no significant difference in hypercalcaemia risk with
vitamin D preparations compared with placebo or no specific treatment (4 studies, 103 children: RD 0.08 mg/dL, 95% CI -0.08 to 0.24). However, there was heterogeneity (I(2) = 55%) with one study showing a significantly greater risk of hypercalcaemia with intravenous (IV)
calcitriol administration. Two studies (97 children) compared
calcitriol with other
vitamin D preparations and both found no significant differences in growth between preparations.Two studies compared
ergocalciferol in patients with CKD and
vitamin D deficiency. Elevated PTH levels developed significantly later in
ergocalciferol treated children (1 study: hazard ratio 0.30, 95% CI 0.09 to 0.93) though the number with elevated PTH levels did not differ between groups (1 study, 40 children: RR 0.33, 95% CI 0.11 to 1.05).Two studies compared
calcium carbonate with
aluminium hydroxide as
phosphate binders. One study (17 children: MD -0.86 SDS, 95% CI -2.24 to 0.52) reported no significant difference in mean final height SDS between treatments. Three studies compared
sevelamer with
calcium-containing
phosphate binders. There were no significant differences in the final
calcium,
phosphorus or PTH levels between binders. More episodes of hypercalcaemia occurred with
calcium-containing binders. One study reported no significant differences between
calcitriol and
doxercalciferol in bone histology or biochemical parameters.
AUTHORS' CONCLUSIONS:
Bone disease, assessed by changes in PTH levels, is improved by all
vitamin D preparations. However, no consistent differences between routes of administration, frequencies of dosing or
vitamin D preparations were demonstrated. Although fewer episodes of high
calcium levels occurred with the non-
calcium-containing
phosphate binder,
sevelamer, compared with
calcium-containing binders, there were no differences in serum
phosphorus and
calcium overall and
phosphorus values were reduced to similar extents. All studies were small with few data available on patient-centred outcomes (growth, bone
deformities) and limited data on biochemical parameters or bone histology resulting in considerable imprecision of results thus limiting the applicability to the care of children with CKD.