Characterization of interleukin-33 and soluble ST2 in serum and their association with disease severity in patients with chronic kidney disease.
ABSTRACT This study aims to test the serum levels of interleukin-33 (IL-33) and soluble ST2 (sST2) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity.
Sixty-nine patients with CKD were enrolled, disease severity was assessed, and clinical data were collected. Twelve healthy volunteers served as healthy individuals. Serum IL-33 and sST2 were tested by enzyme-linked immunosorbent assay.
The patients were classified into five categories based on their estimated glomerular filtration rate (eGFR). No difference was found as to the serum concentration of IL-33 between CKD patients and healthy individuals (p = 0.656), while a higher serum level of sST2 was found in CKD patients (p = 0.003). The correlation analysis revealed a significant correlation between the serum level of sST2 and disease severity (r = 0.586; p < 0.001). A higher level of sST2 was found in CKD patients with elevated parathyroid hormone (p = 0.001). Serum sST2 correlated with parathyroid hormone (r = 0.412; p < 0.001), serum phosphorus (r = 0.545; p < 0.001), and serum calcium (r = -0.494; p < 0.001).
An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: The endogenous molecules high mobility group box 1 (HMGB1) and interleukin-33 (IL-33) have been identified as alarmins, capable of mediating danger signals during tissue damage. Here, we address their possible role as innate-immune mediators in ischemia-reperfusion injury (IRI) following human kidney transplantation. We analysed serum and urinary HMGB1 and IL-33 levels, all determined by enzyme-linked immunosorbent assay, in a cohort of 26 deceased renal transplant recipients. Urinary HMGB1 and IL-33 levels were significantly increased as soon as 30 min after reperfusion, as compared to those before treatment. Moreover, both serum and urinary IL-33 (but not HMGB1) increase was positively correlated with cold ischemia time, from 30 min to 3 days post-transplantation. In vitro, human umbilical vein endothelial cells subjected to hypoxia conditions released both HMGB-1 and IL-33, while only the latter was further increased upon subsequent re-oxygenation. Finally, we postulate that leukocytes from renal recipient patients are targeted by both HMGB1 and IL-33, as suggested by increased transcription of their respective receptors (TLR2/4 and ST2L) shortly after transplantation. Consistent with this view, we found that iNKT cells, an innate-like T cell subset involved in IRI and targeted by IL-33 but not by HMGB1 was activated 1 hour post-transplantation. Altogether, these results are in keeping with a potential role of IL-33 as an innate-immune mediator during kidney IRI in humans.PLoS ONE 02/2014; 9(2):e88742. DOI:10.1371/journal.pone.0088742 · 3.53 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Abstract IL-33 is a proinflammatory cytokine that is a member of IL-1 family. Previously the effect of IL-33 on kidney injury is showed in animal models. In this study, we searched if we can use IL-33 to show the early stage of kidney injury in diabetic patients. Three groups are identified: 26 patients in Group 1: Healthy group, that do not have any chronic diseases and not taking any medication; 42 patients in Group 2: DM (diabetes mellitus) group without any known kidney disease and with normal kidney functions; 32 patients in Group 3: DM + MA (microalbuminuria) group that are assumed to have nephropathy. IL-33 level of DM patient group is greater than healthy group; also IL-33 level of DM + MA patient group is greater than healthy group; but there is not any difference between DM and DM + MA group. The increase in IL-33 levels in diabetic nephropathy is not associated with kidney injury but the increase could be resulting because of diabetes. So IL-33 cannot be used in early recognition of diabetic nephropathy.Renal Failure 09/2013; DOI:10.3109/0886022X.2013.832313 · 0.94 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Soluble ST2 (sST2) provides important prognostic information in patients with heart failure (HF). How sST2 serum concentration is related to renal function is uncertain. We evaluated the association between sST2 and renal function and compared its prognostic value in HF patients with renal insufficiency. Patients (n = 879; median age 70.4 years; 71.8% men) were divided into 3 subgroups according to estimated glomerular filtration rate (eGFR): ≥60 mL/min/1.73 m(2) (n = 337); 30-59 mL/min/1.73 m(2) (n = 352); and <30 mL/min/1.73 m(2) (n = 190). sST2 (rho = -0.16; P < .001), N-terminal pro-B-type natriuretic peptide (rho = -0.40; P < .001), and high-sensitivity cardiac troponin T (rho = -0.47; P < .001) inversely correlated with eGFR. All-cause mortality was the primary end point. During a median follow-up of 3.46 years, 312 patients (35%) died, 246 of them from the subgroup of 542 patients with eGFR <60 mL/min/1.73 m(2) (45%). Biomarker combination including sST2 showed best discrimination, calibration, and reclassification metrics in renal insufficiency patients (net reclassification improvement 16.6 [95% confidence interval (CI) 8.1-25; P < .001]; integrated discrimination improvement 4.2 [95% CI 2.2-6.2; P < .001]). Improvement in reclassification was higher in these patients than in the total cohort. The prognostic value of sST2 was not influenced by renal function. On top of other biomarkers, sST2 improved long-term prediction in patients with renal insufficiency even more than in the total cohort.Journal of cardiac failure 11/2013; 19(11):768-775. DOI:10.1016/j.cardfail.2013.09.005 · 3.07 Impact Factor