ABSTRACT
Objective To explore the effects and mechanisms of losartan on atheroscleorsis and T cell (Treg/Th17) immune balance of CKD apolipoprotein E knockout (ApoE-/-) mice.Methods The model of CKD was induced by a 5/6 nephrectomy (SNx) in male ApoE-/-mice.ApoE-/-mice were randomly allocated into 3 subgroups:the control group,SNx group and losartan group.The fifth week after building model the mice in losartan group were taken losartan at a dose of 30 mg/(kg · d) by intragastric administration for 12 weeks.While the other mice were treated with the same volume of 0.5％ sodium carboxymethylcellulose.Sixteen weeks after nephrectomy,the serum levels of urea and creatinine were determined.Haematoxylin Eosin (HE) staining were used to observe the general morphology changes of atherosclerotic plaque.Flow cytometry was performed to detect the proportion of T cells (Treg/Th17) in spleen.Enzyme linked immunosorbent assay (ELISA) was performed to detect the level of cytokines in serum such as interleukin (IL)-17,IL-6,transforming growth factor-β1 (TGF-β1) and IL-10.Results Sixteen weeks after nephrectomy,the result of serum creatinine and urea nitrogen showed the CKD animal model established successfully.Losartan could improved the renal function of CKD mice.The size of aortic root plaques in control group,SNx group,and losartan group are (16.35 ± 3.72) × 104 μm2,(28.64 ± 5.86) × 104 μm2 and (22.76 ± 3.97) × 104 μ m2 respectively,indicating that losartan treatment significantly decreased the size of aortic root plaques of the CKD mice (P ＜ 0.05).The proportion of Treg cells in the spleen of control group,SNx group,and losartan group are (4.34 ± 0.93) ％,(1.78 ± 0.56) ％,and (2.68 ± 0.58)％ respectively,indicating that losartan treatment significantly increased the proportion of Treg cells of CKD mice (P ＜ 0.01).The proportion of Th17 cells in the spleen of control group,SNx group,and losartan group are (0.11 ± 0.06) ％,(0.67 ± 0.12) ％,(0.37 ± 0.08) ％ respectively,indicating that losartan treatment significantly decreased the proportion of Th17 cells of CKD mice (P ＜ 0.01).Compared with control mice,the level of cytokines TGF-β1 and IL-10 in the serum of the SNx group mice significantly decreased (P ＜0.01),and the level of cytokines IL-17 and IL-6 in the serum of the SNx group mice significantly increased (P ＜0.01),indicating that such effects could be significantly regulated by losartan (P ＜ 0.05).Conclusions Losartan inhibited the differentiation of Th17 cell subsets,promoted the differentiation of Treg,and alleviated atherosclerosis in CKD ApoE-/-mice by modulating the immune imbalance of the Treg/Th17 cell.
ABSTRACT
Objective To investigate the protective effect and the mechanism of amitriptyline on sepsis-induced kidney injury.Methods 48 male Sprague Dawley (SD) rats were randomly divided into six groups:sham group,sham + saline group,sham + amitriptyline group,sepsis group,sepsis + saline group,sepsis + amitriptyline group.Sepsis model was induced by cecal ligation and puncture (CLP).Sham group did not undergo CLP.Amitriptyline were injected subcutaneously to rats with amitriptyline 3 mg/kg before treatment for 10 d,2 times/d,while the control group was injected with the same amount of normal saline.Blood sample was obtained to detect serum level of acid sphingomyelinase (ASMase),ceramide,blood urea nitrogen (BUN),creatinine and interleukin-1β.Malondialdehyde in kidney tissue was determined,and Kidney hematoxylin eosin (HE) staining was performed to observe pathologic change.Another 48 rats were randomly divided into four groups:sham group,sepsis group,sepsis + saline group,sepsis + amitriptyline group.The intervention to each group were same as above description.Rats of the four groups were observed for seven days to determine the survival rate.Results The survival rate of rats in sham group were 100％,the survival rate of the sepsis group and the sepsis + physiological saline group was less than 20％,while the survival rate of the sepsis + amitriptyline group was ＞ 50％.The serum concentration of IL-1β,ceramide,BUN,SCr,the activity of ASMase and the level of malondialdehyde (MDA) in kidney tissue were respectively increased in sepsis group,sepsis + saline group and sepsis + amitriptyline group at the 4 time points were significantly higher than the sham groups (P ＜0.01),these indexes in sepsis plus amitriptyline group were significantly decreased compared to sepsis group (P ＜ 0.01).There was no pathologic change in sham group,sham + saline group and sham + amitriptyline group.In sepsis group and sepsis + saline group,general degeneration and necrosis of renal proximal tubular epithelial cells,marked dilatation of renal tubular capsular space,extensive infiltration of inflammatory cells and hemorrhage in renal interstitium were observed.These pathologic changes were obviously reduced in sepsis + amitriptyline group compared with sepsis group.Conclusions Amitriptyline can alleviate sepsis-induced kidney injury,through inhibiting the activity of ASMase and then restraining inflammatory response and oxidative stress in renal tissues.
ABSTRACT
Objective To investigate the relationship of the neutrophil to lymphocyte ratio (NLR)with stroke in elderly persons with CDK.Methods Totally 220 subjects with stage 3-5 CKD were followed.Fatal and nonfatal cerebrovascular event (CVE) were recorded during this period.NLR at baseline was determined from complete blood count differential.We investigated if NLR could predict stroke.Resuits Median NLR was 2.13.NLR was equally associated with estimated glomerular flitrationrate (eGFR).Totally 116 strokes occurred during follow-up period.NLR could predict stroke independently.Increased NLR over 2.13 was related to a significantly decreased survival time (log-rank Chi-square =4.963,P =0.026).Multivariate Cox regression analysis showed that the risk factor of ischemic stroke in CKD patients was high NLR,hazard ratio (HR) 1.11 [95％ confidence interval (CI) 1.007 to 1.223,P =0.035].Conclusions NLR could independently predict stroke in elderly patients with moderate to severe CKD.
ABSTRACT
Renal protection should be taken into account when we treat chronic gouty arthritis patients combined with chronic kidney disease.Several drugs should be individualized and adjusted dosage according to renal function parameters such as GFR.At the same time,we should closely monitor the side-effects of drugs.
ABSTRACT
Objective To investigate the predictive value of symmetrical ambulatory arterial stiffness index (S-AASI) in detecting early renal impairment of patients with essential hypertension.Methods Totally 245 consecutive out-patients were confirmed with essential hypertension,and were divided into group A (56 cases),group B (64 cases),group C (72 cases),and group D (53 cases) according to the quartile of S-AASI.The combination testing of serum cystatin C,serum β2-microglobulin as well as urine microalbumin to creatinine ratio were implemented as laboratory diagnosis index of renal impairment in early stage and 109 essential hypertension patients were diagnosed with early renal impairment.The parameters were compared among 4 groups.Pearson correlation analysis and partial correlation analysis were performed to confirm the relationship between the markers of early renal impairment and S-AASI.The predictive value of S-AASI to detect early renal injury was evaluated by analyzing Receiver Operating Characteristic (ROC) curve.Results With the rising of S-AASI,age as well as 24 hours mean systolic blood pressure (24 h SBP),serum cystatin C,serum β2-microglobulin,urine microalbumin to creatinine ratio and the incidence rate of early renal injury went notably higher while estimated glomerular filtration rate (eGFR) decreased significantly.After controlling for age,correlation test showed S-AASI was positively correlated with24hSBP,serum cystatin C,serumβ2-microglobulin,urine microalbumin to creatinine ratio(r =0.392,0.627,0.514 and 0.643 respectively,P ＜ 0.05) and negatively correlated with eGFR(r =-0.312,P ＜ 0.05).The 24 hours mean diastolic blood pressure (24 h DBP) was uncorrelated with S-AASI.Area under ROC curve of S-AASI for diagnosis of hypertensive renal impairment was 0.885.The critical value of S-AA-SI was 0.17,the sensitivity,specificity,positive predictive value,and negative predictive value were 92.7％,65.2％,68.5％,and 91.7％,respectively.Conclusions When S-AASI was detected above 0.17,patients with hypertension had a higher risk of renal impairment.Higher S-AASI was correlated with worse early renal impairment laboratory indexes.The predictive accuracy of S-AASI for early hypertensive renal impairment was medium.
ABSTRACT
25-Hydroxyvitamin D deficiency is prevailing in patients with chronic kidney disease,Vitamin D in addition to influence the metabolism of calcium and phosphorus,also participates in regulation of renal anemia.This paper will be reported 25-Hydroxyvitamin D regulates renal anemia from three aspects of the relationship of vitamin D and iron metabolism,erythropoietin (EPO) and micro inflammation.
ABSTRACT
Objective To investigate the alterations of peripheral blood T lymphocyte subsets in patients with sepsis and septic acute kidney injury, and explore the clinical significance.Methods Fifty-five patients with sepsis and forty-three patients with septic acute kidney injury were enrolled in this study. At the same period, thirty healthy subjects were enrolled as the control group.T lymphocyte subsets inclu-ding CD3 +T, CD4 +T, CD8 +T cells, and CD4 +T/CD8 +T in peripheral blood were detected by flow cy-tometry, and acute physiology and chronic health evaluation Ⅱ( APACHE Ⅱ) were graded within twenty-four hours after admission.Then, correlation of the APACHEⅡscores and T lymphocyte subsets was ana-lyzed.Results In the septic acute kidney injury group, peripheral blood CD3 +T, CD4 +T cell percenta-ges, and CD4 +T/CD8 +T ratio were significantly lower than those in the control group and the sepsis group (all P <0.05).In the septic acute kidney injury group with stage 3, CD3+T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio in the patients were significantly lower than those in stage 1 and stage 2 ( all P <0.05).In the septic acute kidney injury group,CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ra-tio were significantly lower in dead group than those in survival group (all P <0.05).APACHEⅡscores in patients with sepsis were significantly negatively correlated with peripheral blood CD4 +T cell percentages and CD4 +T/CD8 +T ratio ( r =-0.645,-0.492, allP <0.05).Conclusions There are varying de-grees of cellular immune imbalance in patients with sepsis and septic acute kidney injury, characterized by decline of circulating CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio.CD4 +T cell percenta-ges and CD4 +T/CD8 +T ratio are closely related to the severity and prognosis of septic acute kidney injury.