Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low.
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.
Litholink® Corporation, 2250 W. Campbell Park Drive, Chicago, IL, 60612, USA. ennisj1@labcorp.com.
Jennifer L
JL
Ennis
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Elaine M
EM
Worcester
Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL, USA.
Fredric L
FL
Coe
Division of Nephrology and Hypertension, NorthShore University HealthSystem, Evanston, IL, USA.
Stuart M
SM
Sprague
D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D002118:Calcium / Q000097:blood; D003430:Cross-Sectional Studies; D003661:Decision Support Techniques; D019587:Dietary Supplements; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D017410:Practice Guidelines as Topic; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy; D012307:Risk Factors; D014481:United States; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy
D015415:Biomarkers; C470125:PTH protein, human; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; C104450:25-hydroxyvitamin D; D002118:Calcium
25-Hydroxyvitamin D; Calcium; Chronic kidney disease; Parathyroid hormone; Phosphorus