Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular EventsReport as inadecuate

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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.


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.


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.


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.

Author: Holly Mansell, Mahmoud Soliman, Hamdi Elmoselhi, Ahmed Shoker

Source: http://plos.srce.hr/


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