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2015 ; 10
(11
): e0142141
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gab.com Text
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Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients
at High Risk for Cardiovascular Events
#MMPMID26544186
Mansell H
; Soliman M
; Elmoselhi H
; Shoker A
PLoS One
2015[]; 10
(11
): e0142141
PMID26544186
show ga
BACKGROUND: The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE)
estimates the burden of cardiovascular risk in renal transplant recipients (RTR).
Our recent study of 95 RTR reported the 7-year median risk of cardiovascular
events (CVE) to be 9.97%, ranging from 1.93 to 84.27%. Nearly a third (28.4%) of
the cohort was above 20% risk for a CVE. Since interleukins (ILs) as part of the
inflammatory response may play a role in the pathogenesis of cardiovascular
disease (CVD), we extended this study to identify which ILs are associated with
high cardiovascular risk in this population. METHODS: Twenty-two ILs were
measured by multiplexed fluorescent bead-based immunoassay in 95 RTR and 56
normal controls. Stepwise analysis after multivariate determination of
significant demographic and inflammatory variables was performed between the high
and low-CVD risk groups (which were arbitrarily set at scores <10% and ?20%,
respectively). Normalized data was presented as mean ± SD and non-normalized data
as median (minimum-maximum). Significance was measured at <0.05. RESULTS: 27.5%
of the low-risk and 31.3% of the high-risk groups had mean IL levels above the 95
percentile of the normal control levels. In the non-parametric analysis IL-6, 9,
16, 17 and 33 were significantly higher in the high-risk group compared to the
control. Univariate analysis (UVA) of the high-risk group identified IL-33 as the
only IL that remained significantly higher than the control and low-risk groups
(p = 0.000). The percentage of patients with IL-33 levels above the 90 percentile
of control value in the low and high-risk groups were 15.6% and 52.0%,
respectively (p<0.002). UVA of factors significant to high IL-33 levels included
estimated glomerular filtration rate (eGFR), while diabetes mellitus, serum
phosphorus, microalbuminuria and age also remained significant in the
multivariate analysis. CONCLUSION: Circulating IL-33 level is positively
associated with high CRCRTR-MACE score. Diminished eGFR, age, diabetes, serum
phosphorus and microalbuminurea demonstrate significant relationship with
elevated IL-33 levels, supporting the possible pathognomonic role of IL-33 in the
cardiovascular burden in RTR.