Secondary Hyperparathyroidism and Vitamin D Receptor Binding to Vitamin D Response Elements in Rats with Incipient Renal Failure

B. Peter Sawaya, Nicholas J. Koszewski, Quanle Qi, M. Chris Langub, Marie Claude Monier-Faugere, Hartmut H. Malluche

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

The pathogenesis of secondary hyperparathyroidism in early renal failure is poorly understood. In the study presented here, parathyroid hormone and GFR in rats with mild renal failure of various durations are evaluated. Parathyroid hormone increased significantly 3 days after nephrectomy and peaked at 2 wk, despite reduction in GFR of <50%. Parathyroid hormone remained elevated, but there was no difference in serum levels of calcium, phosphorus, and calcitriol between the nephrectomized and sham-operated rats. There were also no differences in both intestinal and kidney vitamin D receptor concentrations between the two groups. Histomorphometric analysis of bone at 6 wk revealed significant increase in osteoid thickness, osteoblast number, erosion surface with osteoclasts, and erosion depth. Employing electrophoretic mobility shift assay, we consistently observed a significant reduction in kidney calcitriol-receptor complex binding to mouse osteopontin vitamin D response element (-70.2 ± 4.9%, P <0.001). Western blot analysis also revealed a significant reduction in at least one retinoid X receptor isoform. In conclusion, biochemical and histological evidence of secondary hyperparathyroidism develops in rats with mild renal failure, despite normal calcium, phosphorus, calcitriol, and vitamin D receptor concentrations. These rats also have evidence of reduced renal vitamin D receptor binding to nuclear response elements. This finding, possibly an important early factor in the pathogenesis of secondary hyperparathyroidism, could also play a role in the development of compensatory renal growth of the remnant kidney.

Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalJournal of the American Society of Nephrology
Volume8
Issue number2
StatePublished - Feb 1997

ASJC Scopus subject areas

  • General Medicine

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