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

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Journal of Nephrology Aims and scope Submit manuscript

Abstract

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.

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Conflict of interest

I (J. Ennis) am an employee of Litholink Corporation, a subsidiary of Laboratory Corporation of America (LabCorp), and hold stock in LabCorp. The research conducted was sponsored by this company. E. Worcester, F. Coe, and S. Sprague are consultants for Litholink Corporation and members of the Litholink CKD Scientific Advisory Board. S. Sprague is a consultant for and received honoraria from Amgen, Cytochroma, Kai, and Roche. S. Sprague received grant support from Amgen, Abbott, Cytochroma, NIH, Reata, Shire, and Vifor. All work for this project was undertaken at Litholink Corporation. All authors have made important contributions to the design and execution of this study, the analysis and interpretation of data, and the writing of this manuscript.

Ethical standard

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

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Authors and Affiliations

  1. Litholink® Corporation, 2250 W. Campbell Park Drive, Chicago, IL, 60612, USA

    Jennifer L. Ennis

  2. Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA

    Elaine M. Worcester & Fredric L. Coe

  3. Division of Nephrology and Hypertension, NorthShore University HealthSystem, Evanston, IL, USA

    Stuart M. Sprague

Authors
  1. Jennifer L. Ennis
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  2. Elaine M. Worcester
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  3. Fredric L. Coe
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  4. Stuart M. Sprague
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Corresponding author

Correspondence to Jennifer L. Ennis.

Electronic supplementary material

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40620_2015_186_MOESM1_ESM.jpg

Supplemental Figure S1: Plot of the difference function between linear and cubic regressions of Log Plasma PTH vs 25-D. Coefficients are in Supplemental Table S1. The form of the function is in the footnote to Table S1. Y axis: C = cubic, L = linear predicted values. Zero crossing points are indicated along the horizontal dashed line. The cubic equation departs upward from the linear regression at x values between 42 -48 ng/ml. Stages are represented by panels as in Figure 2 (JPEG 241 kb)

40620_2015_186_MOESM2_ESM.jpg

Supplemental Figure S2: Individual log linear and cubic regressions of Plasma PTH vs 25-D. The crossing points of the linear and cubic equations occur at the points where the difference equation (Figure S1) cross zero. This graph is meant simply to illustrate the 2 regressions visually (JPEG 237 kb)

Supplementary material 3 (DOC 29 kb)

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Ennis, J.L., Worcester, E.M., Coe, F.L. et al. Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low. J Nephrol 29, 63–70 (2016). https://doi.org/10.1007/s40620-015-0186-0

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  • DOI: https://doi.org/10.1007/s40620-015-0186-0

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