Renal osteodystrophy affects nearly an children with chronic renal failure, and growth retardation is a major clinical consequence; accordingly, recombinant human growth hormone (rhGH) has recently been used to enhance linear growth in pediatric patients with end-stage renal disease. Little is known, however, about the effects of rhGH therapy on bone formation and parathyroid gland function in children with renal osteodystrophy. Indeed, most studies have failed to consider whether the type of renal bone disease influences the response to rhGH in children or contributes to the suboptimal response in those undergoing regular dialysis. In the past, secondary hyperparathyroidism was the most common skeletal lesion of renal osteodystrophy in children, but a larger proportion of patients in recent years have histological and/or biochemical evidence of adynamic bone. This disorder is characterized by reduced rates of bone formation, normal or moderately elevated serum PTH levels, and no evidence of bone aluminum deposition. The impact of this disorder on linear growth in children is uncertain, and the role of rhGH as a modifier of PTH-dependent bone turnover in pediatric renal osteodystrophy is currently unknown. This current proposal will characterize the roles of rhGH and calcitriol as modifiers of bone formation and parathyroid gland function in children with selected types of renal bone disease; separate studies will be done for patients with low-turnover and high-turnover skeletal lesions. Bone formation will be evaluated by in cancellous bone by quantitative histomorphometry, and parathyroid gland function will be assessed by in vivo dynamic tests of PTH release. In addition, expression of mRNAs for collagen, alkaline phosphatase and PTH/PTHrP receptor will be determined by in situ hybridization in cancellous bone and in growth plate cartilage in bone biopsy samples from the iliac crest. These studies will provide new information about tissue specific modifiers of cancellous bone formation and endochondral bone formation in children with renal osteodystrophy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK035423-09
Application #
2139565
Study Section
General Medicine B Study Section (GMB)
Project Start
1986-01-01
Project End
1998-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
9
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Hanudel, Mark R; Rappaport, Maxime; Gabayan, Victoria et al. (2017) Increased serum hepcidin contributes to the anemia of chronic kidney disease in a murine model. Haematologica 102:e85-e88
Bacchetta, Justine; Salusky, Isidro B (2016) Combining exercise and growth hormone therapy: how can we translate from animal models to chronic kidney disease children? Nephrol Dial Transplant 31:1191-4
Pereira, Renata C; Bischoff, David S; Yamaguchi, Dean et al. (2016) Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry. Clin J Am Soc Nephrol 11:481-7
Pereira, Renata C; Andersen, Thomas L; Friedman, Peter A et al. (2016) Bone Canopies in Pediatric Renal Osteodystrophy. PLoS One 11:e0152871
Hanudel, Mark R; Wesseling-Perry, Katherine; Gales, Barbara et al. (2016) Effects of acute kidney injury and chronic hypoxemia on fibroblast growth factor 23 levels in pediatric cardiac surgery patients. Pediatr Nephrol 31:661-9
Khouzam, Nadine M; Wesseling-Perry, Katherine; Salusky, Isidro B (2015) The role of bone in CKD-mediated mineral and vascular disease. Pediatr Nephrol 30:1379-88
Pereira, Renata C; Delany, Anne M; Khouzam, Nadine M et al. (2015) Primary osteoblast-like cells from patients with end-stage kidney disease reflect gene expression, proliferation, and mineralization characteristics ex vivo. Kidney Int 87:593-601
Pereira, Renata C; Jüppner, Harald; Gales, Barbara et al. (2015) Osteocytic protein expression response to doxercalciferol therapy in pediatric dialysis patients. PLoS One 10:e0120856

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