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Objective:To investigate interleukin-37 (IL-37) expression in patients with diabetic kidney disease (DKD), and to assess the regulation of exogenous IL-37 on CD8 + T cell function in DKD patients. Methods:A cross-section study was carried out. Twenty healthy controls, thirty-six patients with diabetes mellitus type 2 (T2DM), and forty-seven DKD patients were enrolled in the study. Peripheral blood was collected. Plasma and peripheral blood mononuclear cells were isolated. IL-37 and soluble IL-1 receptor 8 (IL-1R8) levels in the plasma were measured by enzyme-linked immunosorbent assay (ELISA). IL-18 receptor α chain (IL-18Rα), IL-1R8 and immune checkpoint molecules levels in CD8 + T cells were measured by flow cytometry. CD8 + T cells were purified, and were stimulated with recombinant IL-37. CD8 + T cells were co-cultured with HEK293 cells in either direct contact or indirect contact manner. Levels of perforin, granzyme B, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were measured by ELISA. The proportion of target cell death was assessed by measuring lactate dehydrogenase level. Results:Plasma IL-37 levels in DKD patients [(63.42±23.30) ng/L] were significant lower than those in healthy controls [(143.02±50.67) ng/L] and T2DM patients [(87.88±40.62) ng/L] ( t=8.848, P<0.001; t=3.456, P<0.001). Plasma IL-37 level had good predictive values for T2DM in health individuals and for DKD in T2DM patients [the area under the curve was 0.797 (95% CI 0.676-0.917, P<0.001) and 0.691 (95% CI 0.576-0.807, P=0.003), respectively]. Plasma IL-37 level was negatively correlated with urea nitrogen ( r=-0.313, P=0.032) and creatinine ( r=-0.477, P<0.001), and positively correlated with estimated glomerular filtration rate (eGFR) ( r s=0.478, P<0.001) in DKD patients. IL-1R8 + CD8 + cell proportion in DKD patients (33.60%±9.47%) was significantly higher compared to healthy controls (16.29%±5.97%) and T2DM patients (17.13%±4.85%) ( t=7.545, 9.516, both P<0.001), but did not correlate with fast blood glucose, urea nitrogen, creatinine, or eGFR (all P>0.05). There were no statistical differences of IL-18Rα + CD8 + cell proportion, soluble IL-1R8 level, or immune checkpoint molecule proportion in CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). Perforin and granzyme B secretions by CD8 + T cells were significantly elevated in DKD patients compared with healthy controls [(108.78±12.42) ng/L vs. (94.60±10.07) ng/L, t=3.096, P=0.005; (261.34±48.79) ng/L vs. (166.28±30.80) ng/L, t=3.387, P=0.002] and T2DM patients [(108.78±12.42) ng/L vs. (92.58±14.71) ng/L, t=3.263, P=0.003; (261.34±48.79) ng/L vs. (170.66±39.24) ng/L, t=2.627, P=0.014]. There were no significant differences of either IFN-γ or TNF-α secretions by CD8 + T cells among healthy controls, T2DM patients, and DKD patients (all P>0.05). In direct contact co-culture manner, CD8 + T cell-induced HEK293 cell death was down- regulated (13.03%±4.97% vs. 17.88%±5.19%, t=2.235, P=0.037). The levels of perforin [(222.02±25.79) ng/L vs. (294.30±25.58) ng/L, t=6.603, P<0.001], granzyme B [(416.27±90.24) ng/L vs. (524.71±115.53) ng/L, t=2.454, P=0.023], IFN-γ [(23.66±4.20) ng/L vs. (35.18±8.51) ng/L, t=4.026, P<0.001] and TNF-α [(1.62±0.29) μg/L vs. (2.09±0.57) μg/L, t=2.302, P=0.034] were also reduced as well. In indirect contact co-culture manner, there were no significant differences of CD8 + T cell-induced HEK293 cell death, perforin, or granzyme B levels between no stimulation and IL-37 stimulation (all P>0.05). IFN-γ and TNF-α levels in the supernatants were reduced in response to IL-37 stimulation [(23.56±6.24) ng/L vs. (32.56±9.90) ng/L, t=2.550, P=0.019; (1.41±0.31) μg/L vs. (2.10±0.44) μg/L, t=4.011, P<0.001]. Conclusion:IL-37 level is reduced in DKD patients.Exogenous IL-37 suppresses the cytotoxicity of CD8 + T cells in DKD patients.
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Objective To investigate the relationship between the prevalence of isolated systolic hypertension (ISH) and the stages of chronic kidney disease (CKD) in chronic kidney disease outpatient clinic.Methods CKD patients of stages 1,2,3,4 and 5 were recruited (n=626).Based on office systolic pressure (SBP) and diastolic pressure (DBP),they were classified into four subtypes:normotension (＜ 140/90 mmHg),isolated diastolic hypertension (IDH,SBP ＜ 140 mmHg and DBP ≥ 90 mmHg),ISH (SBP≥ 140 mmHg and DBP ＜ 90 mmHg) and systolic-diastolic hypertension (SDH,SBP≥140 mmHg and DBP≥90 mmHg).Results The control rate of blood pressure was 86.4％,75.6％,65.3％,51.0％ and 37.0％ at CKD stage 1,2,3,4 and 5,respectively,which decreased with the advancement of CKD.There was a stepwise increase in the prevalence of ISH (0,9.2％,23.9％,28.6％ and 37.0％ at CKD stage 1,2,3,4 and 5,respectively) and SDH (4.5％,8.4％,8.0％,17.3％,21.9％ at CKD stage 1,2,3,4 and 5,respectively).Logistic regression analysis showed that age,diabetes and CKD stages were independent predictors of ISH.Compared with CKD stage 1-2,CKD stage 3,4 and 5 showed 2.388,2.697 and 5.980 folds risk in developing ISH.Conclusion The prevalence of ISH increases correspondingly with the advancement of stages of CKD,which may partially contribute to the increased cardiovascular mortality during the progress of CKD.
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Objective To investigate whether there is any difference in aortic stiffness among different hypertension subtypes in patients with chronic kidney disease.Methods Six hundred and twenty-six patients with chronic kidney disease were included in the present analysis.They were classified into four groups:normotension (n =391) with systolic blood pressure (SBP) ＜ 140 mmHg and diastolic blood pressure (DBP) ＜ 90 mmHg; isolated systolic hypertension (ISH,n =141) with SBP≥ 140mmHg and DBP ＜ 90 mmHg; isolated diastolic hypertension (IDH,n =25) with SBP ＜ 140 mmHg and DBP≥ 90 mmHg; systolic-diastolic hypertension (SDH,n =69) with SBP≥ 140 mmHg and DBP≥ 90mmHg.Aortic stiffness was assessed by pulse pressure and pulse wave velocity.Results The IDH group had lower mean age than the other groups(P ＜ 0.01).The percentage of diabetes in the ISH group was higher than that in the other groups.The comparison of aortic stiffness showed that the ISH and SDH groups had higher aortic stiffness than the normotension and IDH groups (P ＜ 0.01),but no significant difference in aortic stiffness was observed neither between the normotension and IDH groups nor between ISH and SDH groups.Conclusion Aortic stiffness is significantly different among different hypertension subtypes,which may be an underlying cause for the different cardiovascular mortality among the hypertension subtypes.