Pediatr Nephrol (2008) 23:195–207 Use of sevelamer HCl has also been shown to halt the progression of vascular calcification in patients on dialysis, in contrast to the worsening cardiovascular disease associat- ed with long-term calcium-based binder therapy [47, 94]. Lower mortality rates have also been associated with the use of sevelamer over calcium [97]. Lanthanum carbonate is a non-calcium-containing, but metal-containing (lanthanum), phosphorus binding agent. Several studies have demonstrated that lanthanum carbon- ate effectively reduces serum phosphorous levels, and there are fewer hypercalcemic episodes than with calcium carbonate [98–100]. However, plasma lanthanum levels increase over time. Although levels return to baseline after withdrawal of the drug, bone lanthanum content increases during therapy and remains elevated at least a year after discontinuation of treatment [101]. Further evidence from experiments on rodents indicates progressive liver, bone, and growth plate accumulation [102]. Thus, although lanthanum carbonate is an effective phosphate binder, long-term therapy results in its accumulation in a number of tissues, the long term consequences of which have yet to be defined [103]. In select patient populations and dialysis centers which are able to perform daily hemodialysis, the use of phosphate binding medications may be decreased or entirely avoided. Daily hemodialysis has been demonstrat- ed to normalize serum phosphate levels in these patients, leading to improved nutrition, improved growth, and decreased phosphate binder usage [104, 105]. Secondary hyperparathyroidism 25(OH) vitamin D deficiency is common in children with CKD, and assessment and repletion is recommended for all children in stages 2 to 4 CKD with secondary hyperpara- thyroidism. After repletion of native vitamin D stores, therapy with active vitamin D sterols is effective in suppressing PTH levels to the target range for the stage of CKD. Vitamin D sterols suppress PTH levels by two mechanisms: indirectly, through increased intestinal calci- um absorption, and directly, via suppression of PTH gene transcription. Calcitriol and alfacalcidol are widely used in children, have been shown to be effective in suppressing PTH when given in daily or intermittent doses, and improve growth in children with CKD [39, 40]. However, hypercal- cemia has been linked to their administration, particularly when given with calcium-containing phosphate binders. Thus, newer vitamin D analogues have been developed to maximize affinity for parathyroid tissue, while minimizing effects on intestinal calcium and phosphorus absorption. Three new vitamin D analogues are available for use in patients with CKD: 22-oxacalcitriol (OCT) in Japan, as well as 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol) and 201 1α-hydroxyvitamin D2 (doxercalciferol) in the USA. Oral forms of paricalcitol and doxercalciferol have been ap- proved for CKD 3 through 5 in adults, though not yet in children. Doxercalciferol and paricalcitol are effective in lowering PTH levels and may have a lower calcemic potential than calcitriol in both adults and children with CKD [35, 106]. Calcimimetic agents, which act as allosteric activators of the calcium sensing receptor (CaSR), are also available for the treatment of secondary hyperparathyroidism in the adult dialysis population. By increasing the sensitivity of the CaSR, these small organic molecules are able to reduce PTH levels, decrease the calcium–phosphorus product, and may provide a medical means of halting the progression of parathyroid gland hyperplasia [107]. Cinacalcet has been shown to be effective in the control of secondary hyperparathyroidism in adults with CKD [108], in those treated with maintenance dialysis [109–112], and in those with functioning renal allografts [113]. These agents have not been approved for use in children, and, due to the presence of the CaSR on the growth plate [114], studies are required to confirm their safety and efficacy in young patients. Growth Despite correction of acidosis and optimization of nutrition, many children with CKD continue to grow poorly. Re- combinant growth hormone therapy may be indicated in those whose height is below the 5th percentile for age and who have open epiphyseal plates. Skeletal X-rays to evaluate bone age are indicated prior to initiation of hormone therapy. Skeletal deformities, such as active rickets or slipped capital femoral epiphyses, should be allowed to heal prior to initiation of therapy. Furthermore, since growth hormone therapy may worsen secondary hyperparathyroidism, serum PTH levels must be well controlled prior to start of therapy and should be routinely monitored during treatment. Of note, the clinical response to recombinant growth hormone differs according to stage of CKD, children with stage 5 CKD displaying a less robust growth response than those with less severe kidney disease [115, 116]. Thus, many factors, including growth potential, degree of kidney failure, optimal dialysis prescription [105], concomitant morbidities, and control of renal osteodystrophy, should be considered prior to the initiation of growth hormone therapy. Vascular disease Since cardiovascular disease is the leading cause of death in both adults and children with CKD, the prevention of cardiovascular disease progression is crucial in the man-