Article

Paricalcitol Reduces Albuminuria and Inflammation in Chronic Kidney Disease: A Randomized Double-Blind Pilot Trial

Indiana University and VAMC, 1481 W 10th St, Indianapolis, IN 46202, USA.
Hypertension (Impact Factor: 6.48). 08/2008; 52(2):249-55. DOI: 10.1161/HYPERTENSIONAHA.108.113159
Source: PubMed

ABSTRACT

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 microg of paricalcitol, a vitamin D analog, orally for 1 month. Placebo-corrected change in flow mediated dilatation with a 1-microg dose was 0.5% and 0.4% with a 2-microg 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-microg dose, and 0.5 (95% CI: 0.3 to 0.9; P=0. 03) with a 2-microg 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-microg dose, and 0.54 (95% CI: 0.35 to 0.83; P=0. 01) with a 2-microg 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.

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    • "Among the 31 included studies , one study used the isotope method with 99m Tc DTPA[33]and one study used EDTA to measure GFR before and after clinical intervention[45]. Two studies[24,25]calculated GFR by subcutaneous infusion of nonradioactive iothalamate and one study estimated GFR based on measurement of cystatin C[10]. In most of the included studies, the 24-h urinary creatinine and SCr were evaluated for determination of creatinine clearance and eGFR using the Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault equations. "
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    • "These findings are in conflict with some previous reports. In a placebo-controlled oral study in CKD stages 1–3 patients [53] and in two uncontrolled (intravenous and oral) studies in dialysis patients, a decrease in hs-Crp, IL-6 and TNF-α was found during paricalcitol treatment [54,55]. However, Moe et al. did not find any changes in TNF-α or IL-6 after 12 weeks of treatment with intravenous paricalcitol in a placebo-controlled study in hemodialysis patients with low PTH [56]. "
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