Abstract
ObjectiveIncreased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE).MethodsThis was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1–5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival.ResultsIL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000).ConclusionThis is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients.
Highlights
The prevalence of chronic kidney disease (CKD) in epidemic proportions of the population has increased at a rate of 10.6% to 13.4% [1]
IL-33 and suppression of tumorigenicity 2 (ST2) levels were associated with Flow-mediated dilatation (FMD), and ST2 was a predictor
Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-C-reactive protein (CRP), IL-33, and ST2 were associated with the risk of cardiovascular events (CVE)
Summary
The prevalence of chronic kidney disease (CKD) in epidemic proportions of the population has increased at a rate of 10.6% to 13.4% [1]. Chronic renal failure is a progressive disease. While the transition between stages can sometimes be very fast, it may, in other cases, take years. The most important factors influencing this course are hyperglycaemia, hypertension, high protein diet, and inflammation [2]. Inflammation is an important factor that may play a role in the progression of chronic renal failure and in the progression of other possible complications associated with chronic renal failure [3]. It has been shown that inflammation increases in parallel with increases in CKD stage. While the renal functions decline, the circulating biomarker levels of systemic inflammation—like the CRP, pentraxin-3 (PTX3), interleukin-6 (IL-6), and the anti-inflammatory IL-10—increase constantly [4,5,6]
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