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The treatment goal for secondary hyperparathyroidism (SHPT) is to lower parathyroid hormone (PTH) levels by regaining calcium, vitamin D and phosphorus homeostasis, thus potentially reducing the risks of bone and cardiovascular complications.1–3
The optimal SHPT treatment would:4
However, due to difficulties associated with lowering PTH while simultaneously controlling serum levels of calcium and phosphorous, achieving these goals with traditional therapies can be challenging.5
Current treatment options for SHPT in CKD patients with low vitamin D levels include:6
Many of these treatment options are not indicated for stage 3 or 4 chronic kidney disease (CKD) patients with SHPT and are associated with efficacy or safety limitations (Figure 1).7–14
Adapted from Sprague SM 2017,4 Agarwal R et al. 20167 and 2021,8 Bover J et al. 2021,9 Westerberg PA et al. 2018,10 Petkovich M et al. 2015,11 Li X et al.2015,12 Coyne DW 201313 and Coyne DW 2014.14
Meta-analysis of 14 RCTs (N=974) investigating the effects of NVD supplements on 25(OH)D and PTH in ND-CKD.
Reproduced from Bover J et al. 2021.9
A. Risk of hypercalcaemia in a meta-analysis of six RCTs (n=799) of ND-CKD patients with SHPT, treated with either alfacalcidol or paricalcitol. Odds ratio (OR): 6.63; 95% CI: 2.37, 18.55; p<0.001. B. Risk of hypercalcaemia in a secondary sensitivity analysis of four RCTs (n=512) that excluded the OPERA21 and PRIMO22 studies, which accounted for a large number of the observed hypercalcaemia events. OR: 3.03; 95% CI: 1.06, 8.71; p=0.039.
Adapted from Csomor P et al. 2019.19
*The increase in FGF-23 has been investigated and observed in rats; it has not been investigated in humans.11
†Data are based on a moderate number of studies, with substantial amounts of heterogeneity amongst them.7–9
1,25(OH)2D: 1,25-dihydroxyvitamin D; 25(OH)D: 25-hydroxyvitamin D; AVD: active vitamin D; CI: confidence interval; CKD: chronic kidney disease; CKD–MBD: chronic kidney disease–mineral and bone disorder; CYP24A1: cytochrome P450 family 24 subfamily A member 1; D+L: DerSimonian and Laird method; FGF-23: fibroblast growth factor-23; IR: immediate-release; I-V: inverse variance; KDIGO: Kidney Disease–Improving Global Outcomes; ND-CKD: non-dialysis chronic kidney disease; NVD: nutritional vitamin D; OR: odds ratio; PTH: parathyroid hormone; RCT: randomised controlled trial; SHPT: secondary hyperparathyroidism.
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