Evidence of enhanced systemic inflammation in stable kidney transplant recipients with low Framingham risk scores

Mansell, Holly; Rosaasen, Nicola; Dean, Jonathan; Shoker, Ahmed

doi:10.1111/ctr.12159

Cited by 15 publications

(11 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This explanation is supported by other researchers, who have documented an increase in cardiovascular risk in patients with renal dysfunction (7,8,19). It is also consistent with our previous work, where we observed that impaired renal function was strongly associated with an increase in inflammatory markers, but no relationship was evident between these variables and FRS (25).…”

Section: Discussionsupporting

confidence: 93%

Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients

Benguzzi

Mansell

Hassan

et al. 2014

Clinical Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 93%

Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients

Benguzzi

Mansell

Hassan

et al. 2014

Clinical Transplantation

Self Cite

View full text Add to dashboard Cite

show abstract

“…After a successful renal transplant, the patient’s risk of having a cardiovascular events diminishes, but remains elevated compared to the general population. This is in part due to enhanced circulating chemokine ligand levels [19]. …”

Section: Introductionmentioning

confidence: 99%

Circulating chemokine ligand levels before and after successful kidney transplantation

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundChemokine ligands (CCLs) play a pivotal role in tissue injury before and after kidney transplantation. Meanwhile, transplantation improves patient’s survival and diminishes morbidity. It is hypothesized, then, that kidney transplantation diminishes pre-transplant (pre-TX) levels of circulating inflammatory CCLs. This retrospective study compared circulating levels and profiles of CCLs before transplantation (pre-TX) and after transplantation (post-TX).MethodsNineteen CCLs (1, 2, 3, 4, 5, 8, 11, 13, 15, 17, 21, 24, 26, 27, CXCL 5, 8, 10, 12 and 13) were measured in 47 stable post-TX recipients, and their stored pre-TX plasma was analyzed by multiplexed fluorescent bead-based immunoassay. Twenty normal controls were included for comparisons. Normalized data was presented as mean ± SD and non-normalized data as median (5–95 % CI). Significance was measured at p < 0.01. Arbitrary upper and lower margins for each CCL at the 95 % CI or 2SD levels in each group were chosen to calculate the percentile of patients in the other group who exceeded these limits. Significant CCL levels present in more than 75 % of patients in a group that exceeded the arbitrary upper or lower set margins in the other two groups were labeled as preferentially characteristic for the respective group.ResultsMore than 75 % of pre- and post-TX patients had levels that exceeded the upper control for CCL1, 11, 15 and CCL15, CCL26 and CXCL13 levels, respectively. More than 75 % of pre- and post-TX patients exceeded the lower control for CCL3, 21, and CCL5 limits, respectively. More than 75 % of post-TX patients demonstrated elevated levels of CCL2, 3, 21, 26 and CXCL13 above the upper pre-TX cut offs. Meanwhile, more than 75 % of post-TX patients exceeded the lower pre-TX levels for CCL1, 4, 5, 8, 13, 15, 17, 24 and CXCL8 and10. Pre-TX was preferentially characterized by elevated CCL1 and 15 and diminished CCL3 and 21. Post-TX was preferentially characterized by elevated CCL26 and CXCL13 and diminished CCL4 and 5.ConclusionEnd stage kidney disease is associated with enhanced circulating inflammatory chemokine levels. Stable kidney transplantation is associated with 1) lowered burden of circulating inflammatory chemokine levels and, 2) elevation in the pro T-helper2 chemokine, CCL26 and the homeostatic CXCL13.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-016-0141-4) contains supplementary material, which is available to authorized users.

show abstract

“…Some interleukins were elevated in both patient subgroups (high and low-risk) above control values. They likely contribute to the known systemic inflammatory burden, which is increased in transplantation [ 13 ]. In this study we noticed elevated levels of IL-6, IL-8, IL-9, IL-17 and IL-33 in the high risk group.…”

Section: Discussionmentioning

confidence: 99%

Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular Events

et al. 2015

Self Cite

View full text Add to dashboard Cite

BackgroundThe 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.MethodsTwenty-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.Results27.5% 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.ConclusionCirculating 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.

show abstract

Evidence of enhanced systemic inflammation in stable kidney transplant recipients with low Framingham risk scores

Abstract: Over one half of stable RTR, including those with low FRS, have increased inflammatory chemokine levels. Inflammation is not accounted for in the FRS, and this may explain the poor performance of FRS in transplant patients.

Cited by 15 publications

References 42 publications

Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients

Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients

Circulating chemokine ligand levels before and after successful kidney transplantation

Elevated Circulating Interleukin 33 Levels in Stable Renal Transplant Recipients at High Risk for Cardiovascular Events

Contact Info

Product

Resources

About