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Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular
Holly Mansell1, Mahmoud Soliman2, Hamdi Elmoselhi2
1College of Pharmacy and Nutrition, University of Saskatchewan, Saskatchewan, Canada.
Insights
Interleukin-33 (IL-33) is linked to increased cardiovascular risk in renal transplant recipients (RTR). Elevated IL-33 levels correlate with factors like reduced kidney function and diabetes, suggesting a role in cardiovascular disease pathogenesis.
Area of Science:
- Cardiology
- Nephrology
- Immunology
Background:
- The Major Adverse Cardiovascular Events calculator (CRCRTR-MACE) assesses cardiovascular risk in renal transplant recipients (RTR).
- Previous studies indicated a significant 7-year risk of cardiovascular events (CVE) in RTR, with many patients exceeding a 20% risk threshold.
- Inflammatory markers, such as interleukins (ILs), may contribute to cardiovascular disease (CVD) pathogenesis in this population.
Purpose of the Study:
- To identify specific interleukins (ILs) associated with high cardiovascular risk in renal transplant recipients (RTR).
- To investigate the relationship between IL levels and cardiovascular event risk in RTR.
Main Methods:
- Twenty-two ILs were quantified using multiplexed fluorescent bead-based immunoassay in 95 RTR and 56 controls.
- Stepwise multivariate analysis was employed to identify significant demographic and inflammatory variables differentiating high- and low-CVD risk groups (defined as ≥20% and <10% CRCRTR-MACE scores, respectively).
Main Results:
- Interleukin-33 (IL-33) was significantly elevated in the high-risk group compared to controls and low-risk groups (p = 0.000).
- A higher percentage of high-risk patients (52.0%) exhibited IL-33 levels above the 90th percentile of controls, compared to low-risk patients (15.6%) (p<0.002).
- Factors associated with high IL-33 levels included diminished estimated glomerular filtration rate (eGFR), age, diabetes mellitus, serum phosphorus, and microalbuminuria.
Conclusions:
- Circulating IL-33 levels are positively associated with high CRCRTR-MACE scores in renal transplant recipients (RTR).
- Elevated IL-33 is linked to reduced eGFR, older age, diabetes, higher serum phosphorus, and microalbuminuria.
- These findings support a potential pathognomonic role for IL-33 in the cardiovascular burden experienced by RTR.
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.
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