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Explore the new meta-analysis on NVD for SHPT in ND-CKD

16 September 2021

Can NVD increase 25(OH)D to levels that induce PTH-lowering effects in SHPT?

Bover et al. (2021) have recently published a meta-analysis of randomised controlled trials (RCTs) investigating the effects of nutritional vitamin D (NVD) supplements on 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) in non-dialysis chronic kidney disease (ND-CKD). Using a novel dual analysis approach, the study shines a new light on the underlying mechanisms of vitamin D supplementation in ND-CKD.1

Study goal

The aim of this study was to evaluate the effectiveness of NVD to raise vitamin D and actively lower PTH in ND-CKD patients with secondary hyperparathyroidism (SHPT).1

Study design

Bover et al. conducted a systematic literature review in PubMed to identify 14 RCTs that evaluated one or both of the NVD supplements, ergocalciferol or cholecalciferol, and had a study population of at least 20 adult (>18 years) patients with documented ND-CKD.1 The main results extracted from the studies were changes in absolute values of 25(OH)D, PTH, calcium, phosphate and fibroblast growth factor-23 (FGF-23) from start to end of the study periods.1 Fixed and random effects models were used to pool study-level results and the effects were studied within NVD study arms and relative to control groups (placebo/no treatment).1


Quality of evidence

The evidence was low to moderate in quality due to the number of studies available for inclusion and heterogeneity in study results:1

  • PTH changes within NVD study arms: moderate quality1
  • PTH changes versus placebo/no treatment: low quality1
  • 25(OH)D changes within NVD study arms: low quality1
  • 25(OH)D changes versus placebo/no treatment: very low quality1

Pooled 25(OH)D level increases

NVD supplementation increased levels of 25(OH)D in both analyses:1

  • Increase within NVD study arm: 20.6 ng/mL*
  • Increase versus placebo/no treatment: 26.8 ng/mL*

Average levels of 25(OH)D in the NVD study arms at the end of the study period:1

  • >30 ng/mL in 85.7% (12/14) of the studies
  • >50 ng/mL in 35.7% (5/14) of the studies

Pooled PTH level reductions

Reductions in PTH were observed in both analyses:1

  • Reductions in PTH were small when observed within NVD study arms (pooled reduction of 10.5 pg/mL*)1
  • There were more pronounced reductions when compared with placebo/no treatment (pooled PTH reduction of 49.7 pg/mL*); however, these were due to PTH increases in the comparison group.1

Changes in calcium, phosphate and FGF-23

While small and statistically non-significant changes in phosphate and FGF-23 were observed, NVD supplementation caused calcium levels to significantly increase when compared with placebo/no treatment (increase: 0.23 mg/dL).1

Key takeaways

  • The increases in 25(OH)D levels seen with NVD are often not sufficiently large to induce PTH-lowering effects and to meaningfully reduce levels of PTH in patients with SHPT1
  • NVD has limited potential to raise 25(OH)D above the approximate 50 ng/mL threshold necessary for clinically meaningful PTH responses in ND-CKD patients2,3

You can read the full article published by Bover et al. on the Clinical Kidney Journal website.

Footnotes and references

*From the fixed effects model.1

  1. Bover J et al. Clin Kidney J. 2021;sfab035.

  2. Strugnell SA et al. Am J Nephrol. 2019;49:284–93.

  3. Ennis JL et al. J Nephrol. 2016;29(1):63–70.