Development and progression of secondary hyperparathyroidism in chronic kidney disease: lessons from molecular genetics  William G. Goodman, L.D. Quarles  Kidney International  Volume 74, Issue 3, Pages 276-288 (August 2008) DOI: 10.1038/sj.ki.5002287 Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 1 The respective roles of calcium ions, acting through the CaSR, and vitamin D sterols, acting through the VDR, as direct modifiers of parathyroid gland function. Kidney International 2008 74, 276-288DOI: (10.1038/sj.ki.5002287) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 2 The distribution of calcium among various tissue compartments. A miscible, or rapidly exchangeable, pool of calcium in bone participates in the regulation of plasma calcium homeostasis and serves to maintain a constant level of ionized calcium in blood. Kidney International 2008 74, 276-288DOI: (10.1038/sj.ki.5002287) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 3 Plasma PTH levels (triangles, dashed line, left y-axis) and blood-ionized calcium concentrations (right y-axis) at 1-min intervals in a volunteer with normal renal and parathyroid gland function. Note that plasma PTH levels fluctuate over time, consistent with pulsatile PTH release that is regulated by the CaSR. In contrast, blood-ionized calcium levels remain constant (Goodman, unpublished observations). Kidney International 2008 74, 276-288DOI: (10.1038/sj.ki.5002287) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 4 Plasma PTH levels rise abruptly (a) when blood-ionized calcium concentrations are lowered (b) during intravenous infusions of sodium citrate both in normal volunteers and in patients with bone biopsy-proven hyperparathyroidism due to CKD. Maximum levels are reached within 10–20min, but values do not increase thereafter despite a continued decrease in blood-ionized calcium (from Ramirez et al.43). Kidney International 2008 74, 276-288DOI: (10.1038/sj.ki.5002287) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 5 A graphic depiction of the vitamin D response element (VDRE) and the calcium-response element (CRE) located upstream from the gene for pre-pro-PTH. Both elements negatively regulate gene transcription. Kidney International 2008 74, 276-288DOI: (10.1038/sj.ki.5002287) Copyright © 2008 International Society of Nephrology Terms and Conditions

Figure 6 The percentage changes in plasma PTH levels during intravenous infusions of calcium gluconate in volunteers with normal renal and parathyroid gland function, in patients with bone biopsy-proven hyperparathyroidism due to CKD, in patients with severe SHPT who were few days before undergoing surgical parathyroidectomy, and in patients with primary hyperparathyroidism due to parathyroid adenoma. The non-suppressible component of PTH release differs substantially from normal in each clinical disorder (from Goodman et al.42). Kidney International 2008 74, 276-288DOI: (10.1038/sj.ki.5002287) Copyright © 2008 International Society of Nephrology Terms and Conditions