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- What are the causes of growth failure in children with chronic kidney disease?
Growth failure in a child with CKD is attributed to poor intake, malnutrition,
metabolic acidosis, proteinuria, and renal osteodystrophy. In addition, there is
alteration in GH–IGF1 axis which is characterized by increased GH, normal
total serum IGF1, and reduced free IGF1 levels. Increased GH is due to GH
resistance at hepatocytes and growth plate (as a result of uremia) and decreased
renal clearance of GH. Serum total IGF1 is normal due to decreased clearance
of IGF-binding proteins (IGFBPs), thereby resulting in reduced free IGF1
level. Further, IGF1 resistance at growth plate and use of glucocorticoids con-
tribute to poor linear growth.- How to optimize linear growth in a child with chronic kidney disease?
Optimal nutrition, correction of anemia and metabolic acidosis, near-
normalization of serum calcium, and phosphorus with maintenance of serum
PTH appropriate for CKD stage result in improvement of linear growth in
children with CKD. However, those children who fail to grow despite these
measures should be considered for rhGH therapy. Prior to the initiation of
rhGH therapy, serum phosphate (age specific) and PTH (CKD stage specific)
should be normalized as high PTH levels are detrimental for chondro-osteo-
genesis. The higher doses of rhGH, i.e., 0.35 mg/Kg/week are recommended
as CKD is a GH-resistant state. Serum phosphate and PTH levels should be
monitored, as therapy with rhGH is associated with phosphate retention and
consequent further rise in PTH. There are no adverse effects of rhGH on renal
function; however, increased risk of chronic graft rejection remains a
concern.- How does hypercortisolemia cause short stature?
Hypercortisolemia, whether endogenous or exogenous, in a child is associ-
ated with poor linear growth. The impaired growth is attributed to cortisol-
mediated inhibition of GHRH–GH axis, decreased pre-chondrocyte to
chondrocyte differentiation, increased chondrocyte apoptosis, impaired local
IGF1 generation and action, and increased bone collagen breakdown.
Furthermore, cortisol-mediated suppression of hypothalamo–pituitary–
gonadal axis and alteration in calcium–vitamin D homeostasis (decreased
calcium absorption and hypercalciuria) also contribute to poor linear growth
(Fig. 1.16).1 Disorders of Growth and Development: Clinical Perspectives