Paricalcitol reduces albuminuria and inflammation in CKD—a randomized double-blind pilot trial
Pooneh Alborzi M.D.
Nina A. Patel M.D.
Carla Peterson M.S.
Jennifer E. Bills, B.S.
Dagim M. Bekele, M.D.
Zerihun Bunaye, M.D.
Robert P. Light, B.S.
Rajiv Agarwal M.D.
Indiana University School of Medicine and Richard L. Roudebush Veterans Administration Medical Center, Indianapolis, IN
Correspondence:
Rajiv Agarwal M.D.
Professor of Medicine,
Indiana University and VAMC,
1481 West 10th Street,
Indianapolis, IN 46202
Phone 317-988 2241
Fax 317-988 2171
Email:
Running Head: Paricalcitol in CKD
Online Supplemental Method and Results
Flow Mediated Dilatation
Subjects were studied in a quiet, temperature controlled room by a sonographer using an Acuson Cypress Ultrasound Machine (Siemens Medical, Malvern, PA) equipped with two-dimensional imaging, color and spectral Doppler, an internal electrocardiogram (EKG) monitor and a high frequency vascular transducer (10 mHz). Subjects were asked to refrain from smoking on the day of the study. They were positioned supine with the arm placed in a comfortable position to image the brachial artery in the antecubital fossa in a longitudinal plane. A segment with clear anterior and posterior intimal interfaces between the lumen and the vessel wall was selected. A sphygmomanometeric cuff was placed in the forearm and rapidly inflated to 250 mmHg for 5 minutes to produce ischemia. Rapid cuff inflation was achieved with an air source coupled to a rapid cuff inflator (Hokanson E 20 Rapid Cuff Inflator; E.C. Hokanson, Inc). Longitudinal resting images were acquired before inflation. Blood flow estimated by time-averaging the pulsed Doppler velocity signal obtained from a mid-artery sample volume at baseline and upon immediate cuff release to assess hyperemic velocity. Longitudinal images of the artery were recorded 45 seconds after cuff deflation. Images were recorded digitally for 2 minutes in 32-second intervals. Ten minutes after deflation another image was acquired to reflect a reestablished baseline. A single sublingual 0.4 mg nitroglycerin (NTG) tablet was administered to determine the maximal obtainable vasodilator response to serve as a measure of endothelium-independent vasodilatation reflecting smooth muscle function. Images were continuously recorded starting at 2 minutes 45 seconds after NTG administration. The peak of R-wave was used to measure the brachial artery diameter on a digital imaging station. The change in post stimulus diameter at peak dilation as a percentage of the baseline diameter was reported as endothelial function. The proportion of dilation with NTG was taken to represent vascular smooth muscle function.
Table S1: Flow Mediated Dilatation and Vascular Smooth Muscle FunctionParicalcitol dose (mg/d)
Parameter / 0 / 1 / 2 / P Value between groups
Endothelial Function (Flow Mediated Dilatation)
Baseline (%) / 5.9 / 5.8 / 6.2 / 0.96
95% CI / 4.4 to 7.4 / 4.5 to 7.1 / 4.3 to 8.0
After treatment for 1 month (%) / 5.8 / 6.2 / 6.5 / 0.96
95% CI / 3.9 to 7.8 / 2.9 to 9.6 / 3.2 to 9.7
Mean change Treatment – Baseline / -0.1 / 0.4 / 0.3 / 0.98
95% CI / -2.9 to 2.7 / -2.6 to 3.4 / -3.4 to 4.0
p value within group / 0.95 / 0.79 / 0.87
Mean change compared to placebo / 0.5 / 0.4 / 0.98
95% CI / -5.2 to 6.2 / -5.7 to 6.5
p value within group / 0.86 / 0.9
Smooth Muscle Function (Nitroglycerin induced changes)
Baseline (%) / 10.9 / 13.3 / 11.1 / 0.58
95% CI / 9.0 to 12.8 / 9.1 to 17.6 / 7.8 to 14.4
After treatment for 1 month (%) / 10.8 / 14.2 / 8.8 / 0.35
95% CI / 8.6 to 13.1 / 6.0 to 22.4 / 5.2 to 12.5
Mean change Treatment – Baseline / -0.1 / 0.8 / -2.2 / 0.6
95% CI / -3.1 to 2.9 / -4.6 to 6.3 / -7.2 to 2.8
p value within group / 0.95 / 0.76 / 0.39
Mean change compared to placebo / 0.9 / -2.1 / 0.6
95% CI / -6.6 to 8.5 / -9.3 to 5.1
p value within group / 0.81 / 0.57
Table S2: 24-hour ambulatory blood pressure
Paricalcitol dose (mcg/d)
BP Component / 0 / 1 / 2 / P Value between groups
Systolic Blood Pressure (mm Hg)
Baseline (%) / 130.0 / 121.5 / 124.0 / 0.23
95% CI / 123.2 to 136.8 / 113.8 to 129.1 / 117.4 to 130.5
After treatment for 4 weeks (%) / 124.7 / 124.0 / 128.8 / 0.66
95% CI / 116.7 to 132.8 / 113.2 to 134.7 / 121.0 to 136.6
After washout / 123.6 / 127.6 / 130.6 / 0.65
95% CI / 113.2 to 134.1 / 116.3 to 138.9 / 122.6 to 138.7
Mean change Treatment - Baseline / -5.3 / 2.5 / 4.8 / 0.25
95% CI / -9.7 to -0.8 / -5.3 to 10.3 / -5.5 to 15.2
p value within group / 0.02 / 0.50 / 0.36
Mean change compared to placebo / -1.1 / 2.3 / 1.8 / 0.13
95% CI / -8.0 to 5.7 / -9.0 to 13.7 / -7.4 to 11.0
p value within group / 0.75 / 0.69 / 0.70
Diastolic Blood Pressure (mm Hg)
Baseline (%) / 74.4 / 64.2 / 65.5 / 0.03
95% CI / 67.3 to 81.5 / 61.5 to 66.9 / 60.1 to 70.8
After treatment for 4 weeks (%) / 71.3 / 65.2 / 69.3 / 0.051
95% CI / 66.8 to 75.8 / 60.3 to 70.0 / 64.0 to 74.7
After washout / 70.7 / 70 / 71 / 0.94
95% CI / 64.0 to 77.4 / 64.4 to 75.6 / 65.5 to 76.6
Mean change Treatment - Baseline / -3.1 / 1.0 / 3.9 / 0.31
95% CI / -6.9 to 0.6 / -3.7 to 5.7 / -2.4 to 10.2
p value within group / 0.10 / 0.68 / 0.23
Mean change compared to placebo / -0.6 / 2.9 / 1.7 / 0.08
95% CI / -5.7 to 4.5 / -2.9 to 8.7 / -4.4 to 7.8
p value within group / 0.82 / 0.33 / 0.58
Table S3: Albuminuria changes
Paricalcitol dose (mg/d)
Albuminuria (mg/g creatinine over 24 hr) / 0 / 1 / 2 / P Value between groups
Baseline / 240.6 / 72.2 / 38.6 / 0.08
95% CI / 56.7 to 1022.0 / 30.3 to 171.8 / 18.3 to 81.5
After treatment for 1 month / 324.4 / 37.7 / 20.9 / 0.002
95% CI / 80.6 to 1306.3 / 17.0 to 83.9 / 10.7 to 40.9
After washout / 332.1 / 67.2 / 28.9 / 0.01
95% CI / 80.7 to 1367.1 / 24.4 to 185.2 / 12.7 to 65.5
Mean change Treatment/Baseline / 1.35 / 0.52 / 0.54 / 0.0005
95% CI / 1.08 to 1.69 / 0.40 to 0.69 / 0.35 to 0.83
p value within group / 0.01 / <0.001 / 0.01
Mean change Washout/Treatment / 1.02 / 1.03 / 1.38 / 0.23
95% CI / 0.83 to 1.27 / 0.70 to 1.53 / 0.94 to 2.03
p value within group / 0.83 / 0.87 / 0.10
Analyses were performed on log transformed albumin excretion
Paricalcitol dose (mg/d)
GFR (mL/min) / 0 / 1 / 2 / P Value between groups
Baseline / 57.9 / 38.1 / 49.2 / 0.01
95% CI / 45.3 to 70.5 / 31.8 to 44.4 / 35.6 to 62.9
After treatment for 1 month / 52.3 / 45.0 / 54.5 / 0.48
95% CI / 39.5 to 65.0 / 33.6 to 56.4 / 37.6 to 71.4
After washout / 53.0 / 45.5 / 58.8 / 0.36
95% CI / 38.9 to 67.0 / 32.8 to 58.3 / 40.3 to 77.3
Mean change Treatment – Baseline / -5.6 / 6.9 / 5.3 / 0.26
95% CI / -13.3 to 2.2 / -1.4 to 15.2 / -3.1 to 13.7
p value within group / 0.16 / 0.10 / 0.22
Mean change compared to placebo / 0.7 / -1.7 / 4.3 / 0.27
95% CI / -11.8 to 13.2 / -5.9 to 2.6 / -9.6 to 18.3
p value within group / 0.91 / 0.45 / 0.54
Table S5: Parathyroid Hormone and Vitamin D
Paricalcitol dose (mg/d)
Analyte / 0 / 1 / 2 / P Value between groups
Parathyroid Hormone (pg/mL)
Baseline / 124.9 / 66.8 / 76.0 / 0.18
95% CI / 82.9 to 188.1 / 32.7 to 136.4 / 46.8 to 123.5
After treatment for 1 month / 73.7 / 38.9 / 81 / 0.64
95% CI / 34.0 to 159.6 / 10.1 to 150.2 / 24.0 to 273.8
After washout / 39.2 / 113.4 / 204 / 0.4
95% CI / 8.1 to 189.5 / 18.5 to 694.9 / 44.7 to 931.4
Mean change Treatment/Baseline / 0.6 / 0.6 / 1.1 / 0.64
95% CI / 0.3 to 1.1 / 0.1 to 2.7 / 0.4 to 2.9
p value within group / 0.1 / 0.49 / 0.9
Mean change Washout/Treatment / 0.5 / 1.8 / 2.5 / 0.3
95% CI / 0.1 to 2.4 / 0.4 to 9.3 / 0.5 to 13.2
p value within group / 0.4 / 0.47 / 0.28
25 hydroxy Vitamin D (ng/mL)
Baseline / 14.1 / 14.8 / 11.5 / 0.69
95% CI / 7.8 to 20.4 / 8.9 to 20.7 / 5.6 to 17.4
1, 25 dihydroxy Vitamin D (pg/mL)
Baseline / 20.5 / 25.0 / 27.8 / 0.33
95% CI / 13.3 to 27.8 / 18.1 to 31.8 / 21.0 to 34.6
Analyses were performed on log transformed PTH concentrations.