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

ArticleinHypertension 52(2):249-55 · August 2008with22 Reads
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.
    • "[44,45] Administration of an active VDR agonist has also decreased CRP production independent of its effects on hemodynamics or parathyroid hormone suppression in patients with kidney failure. [46] The current study showed that taking calcium‑Vitamin D supplements for 9 weeks among pregnant women resulted in a significant elevation in plasma TAC levels, but did not affect plasma total GSH. In a study by Ekici et al. [47] increased GSH activity was seen with Vitamin D3 + docosahexaenoic acid supplementation in both cortex and corpus striatum in rats. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Pregnancy is associated with unfavorable metabolic profile, which might in turn result in adverse pregnancy outcomes. The current study was designed to evaluate the effects of calcium plus Vitamin D administration on metabolic status and pregnancy outcomes in healthy pregnant women. Methods: This randomized double-blind placebo-controlled clinical trial was performed among 42 pregnant women aged 18-40 years who were at week 25 of gestation. Subjects were randomly allocated to consume either 500 mg calcium-200 IU cholecalciferol supplements (n = 21) or placebo (n = 21) for 9 weeks. Blood samples were obtained at the onset of the study and after 9-week trial to determine related markers. Post-delivery, the newborn's weight, length, and head circumference were measured during the first 24 h after birth. Results: Consumption of calcium-Vitamin D co-supplements resulted in a significant reduction of serum high-sensitivity C-reactive protein levels compared with placebo (-1856.8 ± 2657.7 vs. 707.1 ± 3139.4 μg/mL, P = 0.006). We also found a significant elevation of plasma total antioxidant capacity (89.3 ± 118.0 vs. -9.4 ± 164.9 mmol/L, P = 0.03), serum 25-hydroxyvitamin D (2.5 ± 3.5 vs. -1.7 ± 1.7 ng/mL, P < 0.0001), and calcium levels (0.6 ± 0.6 vs. -0.1 ± 0.4 mg/dL, P < 0.0001). The supplementation led to a significant decrease in diastolic blood pressure (-1.9 ± 8.3 vs. 3.1 ± 5.2 mmHg, P = 0.02) compared with placebo. No significant effect of calcium-Vitamin D co-supplements was seen on other metabolic profiles. We saw no significant change of the co-supplementation on pregnancy outcomes as well. Conclusions: Although calcium-Vitamin D co-supplementation for 9 weeks in pregnant women resulted in improved metabolic profiles, it did not affect pregnancy outcomes.
    Article · Mar 2016
    • "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. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Vitamin D receptor activators (VDRAs) can protect against mineral bone disease, but they are reported to elevate serum creatinine (SCr) and may also reduce glomerular filtration rate (GFR). Methods: We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) to evaluate the effect of VDRAs on kidney function and adverse events. MEDLINE, EMBASE, the Cochrane Controlled Trials Register were searched for RCTs that evaluate vitamin D receptor activators (alfacalcidol, calcitriol, doxercalciferol, falecalcitriol, maxacalcitol and paricalcitol) up to March 2015. Results: We included 31 studies, all of which were performed between 1976 and 2015, which enrolled 2621 patients. Patients receiving VDRAs had lower eGFR (weighted mean difference WMD -1.29 mL/min /1.73 m2, 95% CI -2.42 to -0.17) and elevated serum creatinine (WMD 7.03 μmol/L, 95% CI 0.61 to 13.46) in sensitivity analysis excluding studies with dropout rate more than 30%. Subgroup analysis of the 5 studies that not use SCr-based measures did not indicated lower GFR in the VDRAs group(WMD -0.97 mL/min/1.73 m2, 95% CI -4.85 to 2.92). Compared with control groups, there was no difference in all-cause mortality (relative risk RR 1.41, 95% CI 0.58 to 3.80), cardiovascular disease (RR 0.84, 95% CI 0.42 to 1.71), and severe adverse events (RR 1.15, 95% CI 0.75 to 1.77) for the VDRAs groups. Episodes of hypercalcemia (RR 3.29, 95% CI 2.02 to 5.38) were more common in the VDRAs group than in the control group. Conclusions: Administration of VDRAs increased serum creatinine levels. Subgroup analysis of studies that did not use SCr-based measures did not indicate a lower GFR in the VDRA group. Future studies with non-SCr-based measures are needed to assess whether the mild elevations of serum creatinine are of clinical significance.
    Full-text · Article · Jan 2016
    • "Clinical studies have also shown that vitamin D can reduce hsCRP levels in CKD patients [3] and in healthy British Bangladeshi adults [45]. Our study results agreed with those of Alborzi et al. [3] showing a trend of increased inflammation in the control group. In the study by Timms et al. [45] on healthy British Bangladeshi adults, supplementation with vitamin D significantly reduced hsCRP levels. "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: To determine the effects of six months alfacalcidol on microvascular endothelial function, arterial stiffness, and BP in DN patients. Methods: Twenty-eight DN patients on alfacalcidol, 0.25 μg daily for six months were compared to 32 controls on conventional treatment. Measurements of microvascular endothelial function, arterial stiffness [AIx and PWV], hsCRP, and BP were performed; differences between baseline and six months treatment were evaluated. Results: No difference was seen in microvascular endothelial function for both groups after six months. Improvement in CSBP (p = 0.027) with trends of improvement in AIx (p = 0.063), PWV (p = 0.075), and systolic BP (p = 0.088) were seen in the alfacalcidol group with no changes observed in controls. Subgroup analysis of alfacalcidol group showed that vitamin D-deficient patients had better response to treatment. hsCRP level remained unchanged in alfacalcidol group; significant increase was however seen in controls. Conclusion: Alfacalcidol did not have an effect on microvascular endothelial function in DN patients. Alfacalcidol significantly improved CSBP with trends of improvement in arterial stiffness and peripheral BP. Alfacalcidol appears to be more beneficial in vitamin D-deficient patients.
    Full-text · Article · Nov 2015
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