Abnormal parathyroid gland function in CKD

Lewin, Ewa; Rodríguez, Mariano; Ølgaard, Klaus; Salusky, I. B.; Silver, Justin

doi:10.1093/med/9780199559176.003.006

Cited by 4 publications

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“…As s-HPT gets worse, the glands become unresponsive to vitamin D and calcium therapy, indicating that the parathyroid cells with low expression of CaR and/or VDR can no longer convey calcium or vitamin D signals. Lewin et al showed in 2002 that plasma PTH, together with plasma Ca 2+ , phosphate, creatinine, and urea, normalized after an experimental isogenic kidney transplantation in rats, despite persistently low parathyroid expression of CaR and VDR ; only several weeks later did the expression of CaR and VDR become normal in the parathyroids [ 2 , 35 , 36 ]. The delay in the restored expression of CaR and VDR in this model of reversal of uremia by Lewin et al stresses the importance of a search for not-yet-identified mechanisms that might control CaR and VDR genes in the parathyroids.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Methylation of ParathyroidCaRandVDRPromoters in Experimental Secondary Hyperparathyroidism

Hofman-Bang

Gravesen

Ølgaard

et al. 2012

International Journal of Nephrology

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Secondary hyperparathyroidism (s-HPT) in uremia is characterized by decreased expression in the parathyroids of calcium sensing (CaR) and vitamin D receptors (VDR). Parathyroid hormone (PTH) is normalized despite low levels of CaR and VDR after experimental reversal of uremia. The expression of CaR in parathyroid cultures decreases rapidly. Methylation of promoter regions is often detected during epigenetic downregulation of gene expression. Therefore, using an experimental rat model, we examined changes in methylation levels of parathyroid CaR and VDR promoters in vivo and in vitro. Methods. Uremia was induced by 5/6 nephrectomy. Melting temperature profiling of CaR and VDR PCR products after bisulfite treatment of genomic DNA from rat parathyroids was performed. Real-time PCR measured expression of PTH, CaR, VDR, and klotho genes in vitro. Results. Parathyroids from uremic rats had similar low levels of methylation in vivo and in vitro. In culture, a significant downregulation of CaR, VDR, and klotho within two hours of incubation was observed, while housekeeping genes remained stable for 24 hours. Conclusion. In uremic s-HPT and in vitro, no overall changes in methylation levels in the promoter regions of parathyroid CaR and VDR genes were found. Thus, epigenetic methylation of these promoters does not explain decreased parathyroid expression of CaR and VDR genes in uremic s-HPT.

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Section: Discussionmentioning

confidence: 99%