Paricalcitol does not improve glucose metabolism in patients with stage 3-4 chronic kidney disease

Ian H de Boer, Michael Sachs, Andrew N Hoofnagle, Kristina M Utzschneider, Steven E Kahn, Bryan Kestenbaum, Jonathan Himmelfarb, Ian H de Boer, Michael Sachs, Andrew N Hoofnagle, Kristina M Utzschneider, Steven E Kahn, Bryan Kestenbaum, Jonathan Himmelfarb

Abstract

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.

Figures

Figure 1. Enrollment, randomization, and follow-up of…
Figure 1. Enrollment, randomization, and follow-up of study participants
Figure 2. Mean plasma concentrations of glucose…
Figure 2. Mean plasma concentrations of glucose (A), insulin (B), and free fatty acids (C) by treatment period
Mean ± SD are presented for each time point.
Figure 3. Effects of paricalcitol on glucose…
Figure 3. Effects of paricalcitol on glucose tolerance for each individual study participant
Glucose tolerance is measured as glucose area under the curve (AUC) from oral glucose tolerance tests. Individual glucose AUC values measured at the end of each participant’s paricalcitol treatment period and the end of each participant’s placebo treatment period. The open circle (with dotted line) represents glucose AUC at the beginning of the paricalcitol treatment period for the one participant who did not complete placebo treatment.
Figure 4. Effects of paricalcitol on glucose…
Figure 4. Effects of paricalcitol on glucose tolerance among subsets of participants defined by baseline characteristic
Geometric mean fold change in glucose area under the curve (AUC) during oral glucose tolerance tests, comparing values from the end of the paricalcitol treatment period to the end of the placebo period, are presented on the X axis with 95% confidence interval. Numbers of participants in each subgroup are listed on the left. eGFR = estimated glomerular filtration rate; PTH = parathyroid hormone; 1,25(OH)2D = 1,25-dihydroxyvitamin D; 25(OH)D = 25-hydroxyvitamin D.

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