Current treatment options for secondary hyperparathyroidism in patients with stage 3 to 4 chronic kidney disease and vitamin D deficiency

Expert Opin Drug Saf. 2021 Nov;20(11):1333-1349. doi: 10.1080/14740338.2021.1931117. Epub 2021 Jun 9.


Introduction: Secondary hyperparathyroidism (SHPT) represents a complication of chronic kidney disease (CKD). Vitamin D system is altered since early CKD, and vitamin D deficiency is an established trigger of SHPT. Although untreated SHPT may degenerate into tertiary hyperparathyroidism with detrimental consequences in advanced CKD, best treatments for counteracting SHPT from stage 3 CKD are still debated. Enthusiasm on prescription of vitamin D receptor activators (VDRA) in non-dialysis renal patients, has been mitigated by the risk of low bone turnover and positive calcium-phosphate balance. Nutritional vitamin D is now suggested as first-line therapy to treat SHPT with low 25(OH)D insufficiency. However, no high-grade evidence supports the best choice between ergocalciferol, cholecalciferol, and calcifediol (in its immediate or extended-release formulation).Areas covered: The review discusses available data on safety and efficacy of nutritional vitamin D, VDRA and nutritional therapy in replenishing 25(OH)D deficiency and counteracting SHPT in non-dialysis CKD patients.Expert opinion: Best treatment for low 25(OH)D and SHPT remains unknown, due to incomplete understanding of the best homeostatic, as mutable, adaptation of mineral metabolism to CKD progression. Nutritional vitamin D and nutritional therapy appear safest interventions, whenever contextualized with single-patient characteristics. VDRA should be restricted to uncontrolled SHPT by first-line therapy.

Keywords: 25(Oh)D; CKD; Secondary hyperparathyroidism; VDRA; calcifediol; cholecalciferol; nutritional therapy.

Publication types

  • Review

MeSH terms

  • Dietary Supplements
  • Disease Progression
  • Humans
  • Hyperparathyroidism, Secondary / etiology
  • Hyperparathyroidism, Secondary / therapy*
  • Receptors, Calcitriol / drug effects
  • Receptors, Calcitriol / metabolism
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / physiopathology
  • Vitamin D / administration & dosage
  • Vitamin D / adverse effects
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / therapy


  • Receptors, Calcitriol
  • Vitamin D