Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease - PubMed (original) (raw)

Randomized Controlled Trial

Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease

J A Alvarez et al. Eur J Clin Nutr. 2013 Mar.

Erratum in

Abstract

Background/objectives: Vitamin D has anti-inflammatory and immune-regulating properties. We aimed to determine if high-dose cholecalciferol supplementation for 1 year in subjects with early chronic kidney disease (CKD) improved circulating markers of inflammation and immunity.

Subjects/methods: In this double-blind, randomized, placebo-controlled trial, 46 subjects with early CKD (stages 2 and 3) were supplemented with oral cholecalciferol (50 000 IU weekly for 12 weeks followed by 50 000 IU every other week for 40 weeks) or a matching placebo for 1 year. Serum tumor necrosis factor-α, interleukin-6, monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein-10 and neutrophil gelatinase-associated lipocalin were measured at baseline, 12 weeks and 1 year. Serum cathelicidin (LL-37) was measured at baseline and 12 weeks. An in vitro experiment was performed to investigate the effect of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment on MCP-1 secretion in THP-1 monocytes activated with lipopolysaccharide (LPS) and Pseudomonas aeruginosa.

Results: By 12 weeks, serum MCP-1 decreased in the cholecalciferol group (66.2±2.5 to 60.8±2.6 pg/ml, group-by-time interaction P=0.02) but was not different from baseline at 1 year. Other markers of inflammation and immunity did not change. In vitro, LPS- and Pseudomonas-activated monocytes treated with 1,25(OH)2D3 had significantly less MCP-1 secretion compared with untreated cells.

Conclusions: High-dose cholecalciferol decreased serum MCP-1 concentrations by 12 weeks in patients with early CKD, although the decrease was not maintained for the remainder of the year. In vitro results confirm an MCP-1-lowering effect of vitamin D. Future studies should determine if vitamin D-mediated reductions in MCP-1 concentrations reflect improved clinical outcomes.

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Conflict of interest statement

CONFLICT OF INTEREST

The authors have no conflicts of interest to declare.

Figures

Figure 1

Figure 1. Relationship between baseline monocyte chemoattractant protein-1 (MCP-1) and baseline 25-hydroxyvitamin D [25(OH)D]

Baseline concentrations of serum MCP-1 were significantly, inversely associated with baseline serum 25(OH)D in patients with early stage chronic kidney disease (n = 43).

Figure 2

Figure 2. Relationship between percent change in 25-hydroxyvitamin D [25(OH)D] and percent change in monocyte chemoattractant protein-1 (MCP-1) at 12 wks

After receiving 50 000 IU cholecalciferol weekly for 12 wks or matching placebo, the percent change in 25(OH)D was significantly, inversely associated with percent change in MCP-1 in patients with early stage chronic kidney disease (n = 37).

Figure 3

Figure 3. 1,25-dihydroxyvitamin D3 reduces monocyte chemoattractant protein-1 (MCP-1) release from activated monocytes

Human THP-1 monocyte cells were treated with 40nM of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) for 48 hr prior to activation with 10 pmol/mL of purified lipopolysaccharide (LPS) (A) or infection with Pseudomonas aeruginosa at 10 MOI (B). MCP-1 release into the supernatants of activated monocytes was measured by ELISA. Error bars represent ± SD of triplicate readings of each sample. _P_-value was calculated using the Student t-test.

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