Short-term vitamin D receptor activation increases serum creatinine due to increased production with no effect on the glomerular filtration rate

Kidney Int. 2011 Nov;80(10):1073-9. doi: 10.1038/ki.2011.207. Epub 2011 Jun 29.


Vitamin D receptor activation has been associated with increased serum creatinine and reduced estimated glomerular filtration rates, raising concerns that its use may be detrimental to kidney function. Here we studied the effect of vitamin D receptor activation on serum creatinine, creatinine generation, and its clearance. We measured baseline serum creatinine and 24-h urine creatinine in 16 patients with chronic kidney disease. The measurements were repeated every day for 7 days, during which time the patients received 2 μg paricalcitol, an orally active vitamin D receptor activator, every morning. At 4 days after stopping the vitamin analog, measurements were continued for 3 days. Geometric mean parathyroid hormone levels decreased from 77 pg/ml at baseline to 43 pg/ml at the end of treatment and significantly rebounded to 87 pg/ml following paricalcitol withdrawal, thereby supporting the biological efficacy of the analog dose used. With this therapy, the serum creatinine significantly increased at a rate of 0.010 mg/dl/day and urine creatinine at a rate of 17.6 mg/day. Creatinine and iothalamate clearances did not change, whereas urine albumin decreased insignificantly. Thus, short-term vitamin D receptor activation increases creatinine generation and serum creatinine, but it does not influence the glomerular filtration rate.

Trial registration: NCT01163162.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Albuminuria / blood
  • Albuminuria / drug therapy
  • Albuminuria / physiopathology
  • Albuminuria / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Chronic Disease
  • Creatinine / blood*
  • Creatinine / urine
  • Drug Administration Schedule
  • Ergocalciferols / administration & dosage*
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Indiana
  • Iothalamic Acid
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Diseases / blood
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / physiopathology
  • Kidney Diseases / urine
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Receptors, Calcitriol / agonists*
  • Receptors, Calcitriol / metabolism
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Ergocalciferols
  • PTH protein, human
  • Parathyroid Hormone
  • Receptors, Calcitriol
  • Iothalamic Acid
  • paricalcitol
  • Creatinine

Associated data