Paricalcitol does not improve glucose metabolism in patients with stage 3-4 chronic kidney disease.
Patients with chronic kidney disease are often insulin resistant and glucose intolerant--abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end-stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analog, changes glucose tolerance in earlier stages of chronic kidney disease. In a crossover design, 22 nondiabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose of 100-125 mg/dl were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in nondiabetic patients with stage 3-4 chronic kidney disease.
Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington 98104, USA. deboer@u.washington.edu
Ian H
IH
de Boer
Michael
M
Sachs
Andrew N
AN
Hoofnagle
Kristina M
KM
Utzschneider
Steven E
SE
Kahn
Bryan
B
Kestenbaum
Jonathan
J
Himmelfarb
D000368:Aged; D018592:Cross-Over Studies; D004872:Ergocalciferols / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D018167:Receptors, Calcitriol / Q000819:agonists; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism
D004872:Ergocalciferols; D018167:Receptors, Calcitriol; D014807:Vitamin D; C084656:paricalcitol; C104450:25-hydroxyvitamin D; D005947:Glucose