The spectrum of renal osteodystrophy has been very well characterized by bone histomorphometry in patients treated with dialysis. However, it was only with the availability of the first generation immunometric PTH assay (1st PTH-IMA) that such measurements have emerged as relatively accurate predictors of the skeletal lesion of renal osteodystrphy. However, the relationship between PTH and bone formation was altered by intermittent calcitriol therapy. Similar studies have not been carried out in children with chronic kidney disease (CKD) before dialysis for more than two decades. Despite this lack of data, PTH determinations are commonly used as surrogate markers of bone formation and turnover, and therapy with calcitriol is recommended to those patients to prevent growth retardation and bone deformities. Furthermore, the prediction of bone turnover is further complicated because their interpretation is confounded by the stage of CKD and that it appears likely to reflect progression of the state of skeletal resistance to PTH. It is now known that 1st PTH-IMA detect not only PTH(1-84), but also large amino-terminally truncated PTH fragments, some of which were shown to have hypocalcemic properties in vivo and diminish bone turnover. In contrast, recent developed second generation immunometric PTH (2nd PTH-IMA) that recognize only PTH(1-84), but not naturally occurring fragments of the intact hormone. The current proposal will determine: 1) whether PTH concentrations measured by 2nd PTH-IMA provide a more accurate assessment of bone formation and turnover than 1st PTH-IMA in children, adolescents and young adults with CKD prior to dialysis and those undergoing chronic hemodialysis. 2) To assess the magnitude and progression of renal and skeletal resistance to PTH and to determine whether the abundance of amino-terminally truncated PTH (1-84) fragments contribute to the state of resistance in such patients. Bone formation will be evaluated in cancellous bone by quantitative histomorphometry, renal and skeletal resistance to PTH will be assessed by PTH(1-34) infusions. The results of the study should provide new information on the relationship between PTH and bone formation in CKD and they are likely to have important implications for the diagnosis and treatment of renal osteodystrophy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK067563-05
Application #
7566021
Study Section
Skeletal Biology Development and Disease Study Section (SBDD)
Program Officer
Moxey-Mims, Marva M
Project Start
2005-02-15
Project End
2012-01-31
Budget Start
2009-02-01
Budget End
2012-01-31
Support Year
5
Fiscal Year
2009
Total Cost
$363,655
Indirect Cost
Name
University of California Los Angeles
Department
Pediatrics
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Hanudel, Mark R; Froch, Larry; Gales, Barbara et al. (2017) Fractures and Osteomalacia in a Patient Treated With Frequent Home Hemodialysis. Am J Kidney Dis 70:445-448
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
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; J├╝ppner, Harald; Gales, Barbara et al. (2015) Osteocytic protein expression response to doxercalciferol therapy in pediatric dialysis patients. PLoS One 10:e0120856
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
Zaritsky, Joshua; Rastogi, Anjay; Fischmann, George et al. (2014) Short daily hemodialysis is associated with lower plasma FGF23 levels when compared with conventional hemodialysis. Nephrol Dial Transplant 29:437-41

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