Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low

J Nephrol. 2016 Feb;29(1):63-70. doi: 10.1007/s40620-015-0186-0. Epub 2015 Mar 4.


Objective: It is uncertain whether increasing 25-hydroxyvitamin D (25-D) levels in chronic kidney disease (CKD) patients above those recommended by current guidelines result in progressive amelioration of secondary hyperparathyroidism. Our objective was to identify a potential therapeutic 25-D target which optimally lowers plasma parathyroid hormone (PTH) without producing excessive hypercalcemia or hyperphosphatemia in CKD.

Methods: We performed a cross-sectional analysis of 14,289 unselected stage 1-5 CKD patients from US primary care and nephrology practices utilizing a laboratory-based CKD clinical decision support service between September 2008 and May 2012. Estimated glomerular filtration rate (eGFR), plasma PTH, and serum 25-D, calcium, and phosphorus results were analyzed.

Results: In CKD stages 3-5, progressively higher 25-D pentiles contained progressively lower mean PTH levels. Regression analysis of log PTH on 25-D was significant in all CKD stages with no evidence of a decreasing effect of 25-D to lower PTH until 25-D levels of 42-48 ng/ml. Progressively higher 25-D concentrations were not associated with increased rates of hypercalcemia or hyperphosphatemia.

Conclusions: We found evidence for an optimal level of 25-D above which suppression of PTH progressively diminishes. This level is more than twice that currently recommended for the general population. We found no association between these higher 25-D levels and hyperphosphatemia or hypercalcemia. Additional prospective trials seem appropriate to test the idea that 25-D levels around 40-50 ng/ml could be a safe and effective treatment target for secondary hyperparathyroidism in CKD.

Keywords: 25-Hydroxyvitamin D; Calcium; Chronic kidney disease; Parathyroid hormone; Phosphorus.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Algorithms
  • Biomarkers / blood
  • Calcium / blood
  • Cross-Sectional Studies
  • Decision Support Techniques
  • Dietary Supplements
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / diagnosis
  • Hyperparathyroidism, Secondary / etiology*
  • Least-Squares Analysis
  • Linear Models
  • Male
  • Middle Aged
  • Nonlinear Dynamics
  • Parathyroid Hormone / blood
  • Phosphorus / blood
  • Practice Guidelines as Topic
  • Prognosis
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / therapy
  • Risk Factors
  • United States
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / diagnosis
  • Vitamin D Deficiency / drug therapy


  • Biomarkers
  • PTH protein, human
  • Parathyroid Hormone
  • Vitamin D
  • Phosphorus
  • 25-hydroxyvitamin D
  • Calcium