Growth retardation is a major obstacle to full rehabilitation of children w
ith chronic renal failure (CRF), Several factors have been identified as co
ntributors to impaired linear growth and they include protein and calorie m
alnutrition, metabolic acidosis, growth hormone resistance, anemia, and ren
al osteodystrophy, Although therapeutic interventions such as the use of re
combinant human growth hormone, recombinant human erythropoietin, and calci
triol have made substantial contributions, the optimal therapeutic strategy
remains to be defined. Indeed, growth failure persists in a substantial pr
oportion of children with renal failure and those treated with maintenance
dialysis, In addition, the increasing prevalence of adynamic lesions of ren
al osteodystrophy and its effect on growth have raised concern about the co
ntinued generalized use of calcitriol in children with CRF, Recent studies
have shown the critical roles of parathyroid hormone-related protein (PTHrP
) and the PTH/PTHrP receptor in the regulation of endochondral bone formati
on, The PTH/PTHrP receptor mRNA expression has been shown to he down-regula
ted in kidney and growth plate cartilage of animals with renal failure. Dif
ferences in the severity of secondary hyperparathyroidism influence not onl
y growth plate morphology but also the expression of selected markers of ch
ondrocyte proliferation and differentiation in these animals. Such findings
suggest potential molecular mechanisms by which cartilage and bone develop
ment may be disrupted in children with CRF, thereby contributing to diminis
hed linear growth.