Paricalcitol reduces albuminuria and inflammation in chronic kidney disease - A randomized double-blind pilot trial

被引:282
作者
Alborzi, Pooneh [1 ]
Patel, Nina A. [1 ]
Peterson, Carla [1 ]
Bills, Jennifer E. [1 ]
Bekele, Dagim M. [1 ]
Bunaye, Zerihun [1 ]
Light, Robert P. [1 ]
Agarwal, Rajiv [1 ,2 ,3 ]
机构
[1] Indiana Univ, Sch Med, Indianapolis, IN 46202 USA
[2] VAMC, Indianapolis, IN 46202 USA
[3] Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN USA
关键词
chronic kidney disease; vitamin D; albuminuria; ambulatory blood pressure; inflammation; endothelial function;
D O I
10.1161/HYPERTENSIONAHA.108.113159
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Vitamin D receptor activation is associated with improved survival in patients with chronic kidney disease, but the mechanism of this benefit is unclear. To better understand the effects of vitamin D on endothelial function, blood pressure, albuminuria, and inflammation in patients with chronic kidney disease ( 2 patients stage 2, remaining stage 3), we conducted a pilot trial in 24 patients who were randomly allocated equally to 3 groups to receive 0, 1, or 2 mu g of paricalcitol, a vitamin D analog, orally for 1 month. Placebo-corrected change in flow mediated dilatation with a 1-mu g dose was 0.5% and 0.4% with a 2-mu g dose ( P > 0.2). At 1 month, the treatment: baseline ratio of high sensitivity C-reactive protein was 1.5 ( 95% CI: 1.1 to 2.1; P = 0.02) with placebo, 0.8 ( 95% CI: 0.3 to 1.9; P = 0.62) with a 1-mu g dose, and 0.5 ( 95% CI: 0.3 to 0.9; P = 0. 03) with a 2-mu g dose of paricalcitol. At 1 month, the treatment: baseline ratio of 24-hour albumin excretion rate was 1.35 ( 95% CI: 1.08 to 1.69; P = 0.01) with placebo, 0.52 ( 95% CI: 0.40 to 0.69; P < 0.001) with a 1-mu g dose, and 0.54 ( 95% CI: 0.35 to 0.83; P = 0. 01) with a 2-mu g dose ( P < 0.001 for between group changes). No differences were observed in iothalamate clearance, 24- hour ambulatory blood pressure, or parathyroid hormone with treatment or on washout. Thus, paricalcitol- induced reduction in albuminuria and inflammation may be mediated independent of its effects on hemodynamics or parathyroid hormone suppression. Long- term randomized, controlled trials are required to confirm these benefits of vitamin D analogs.
引用
收藏
页码:249 / 255
页数:7
相关论文
共 35 条
  • [1] Antiproteinuric effect of oral paricalcitol in chronic kidney disease
    Agarwal, R
    Acharya, M
    Tian, J
    Hippensteel, RL
    Melnick, JZ
    Qiu, P
    Williams, L
    Batlle, D
    [J]. KIDNEY INTERNATIONAL, 2005, 68 (06) : 2823 - 2828
  • [2] Agarwal R, 1998, J CHROMATOGR B, V705, P3
  • [4] Liquid chromatography for iothalamate in biological samples
    Agarwal, R
    Vasavada, N
    Chase, SD
    [J]. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES, 2003, 785 (02): : 345 - 352
  • [5] Vitamin D in chronic kidney disease: A systemic role for selective vitamin D receptor activation
    Andress, DL
    [J]. KIDNEY INTERNATIONAL, 2006, 69 (01) : 33 - 43
  • [6] Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals
    Bodyak, Natalya
    Ayus, Juan Carlos
    Achinger, Steven
    Shivalingappa, Venkatesha
    Ke, Qingen
    Chen, Yee-Shiuan
    Rigor, Debra L.
    Stillman, Isaac
    Tamez, Hector
    Kroeger, Paul E.
    Wu-Wong, Ruth R.
    Karumanchi, S. Ananth
    Thadhani, Ravi
    Kang, Peter M.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (43) : 16810 - 16815
  • [7] Differences in urinary albumin detected by four immunoassays and high-performance liquid chromatography
    Comper, WD
    Jerums, G
    Osicka, TM
    [J]. CLINICAL BIOCHEMISTRY, 2004, 37 (02) : 105 - 111
  • [8] Plasma 25-hydroxyvitamin D levels and risk of incident hypertension
    Forman, John P.
    Giovannucci, Edward
    Holmes, Michelle D.
    Bischoff-Ferrari, Heike A.
    Tworoger, Shelley S.
    Willett, Walter C.
    Curhan, Gary C.
    [J]. HYPERTENSION, 2007, 49 (05) : 1063 - 1069
  • [9] 1,25-Dihydroxyvitamin D3 up-regulates the renal vitamin D receptor through indirect gene activation and receptor stabilization
    Healy, KD
    Frahm, MA
    DeLuca, HF
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2005, 433 (02) : 466 - 473
  • [10] 1α,25-dihydroxyvitamin D3 is a potent suppressor of interferon γ-mediated macrophage activation
    Helming, L
    Böse, J
    Ehrchen, J
    Schiebe, S
    Frahm, T
    Geffers, R
    Probst-Kepper, M
    Balling, R
    Lengeling, A
    [J]. BLOOD, 2005, 106 (13) : 4351 - 4358