Resolvin D1 Protects Lipopolysaccharide-induced Acute Kidney Injury by Down-regulating Nuclear Factor-kappa B Signal and Inhibiting Apoptosis

Background： Resolvin D1 （RvD1） is a newly found anti-inflammatory bioactive compound derived from polyunsaturated fatty acids. The current study aimed to explore the protective effect of RvD1 on lipopolysaccharide （LPS）-induced acute kidney injury （AKI） and its possible mechanism. Methods： Both in vivo and in vitro studies were conducted. Male BALB/c mice were randomly divided into control group （saline）, LPS group （LPS 5 mg/kg）, RvD1 group （RvD1 5 μg/kg ＋ LPS 5 mg/kg）, and blockage group （Boc-MLP 5 gg/kg ＋ RvD1 5 gg/kg ＋ LPS 5 mg/kg）. Boc-MLP is a RvD 1 receptor blocker. The mice were intraperitoneally injected with these drugs and recorded for general condition for 48 h, while the blood and kidneys were harvested at 2, 6, 12, 24, and 48 h time points, respectively （n = 6 in each group at each time point）. Human proximal tubule epithelial cells （HK-2） were randomly divided into control group （medium only）, LPS group （LPS 5 μg/ml）, RvD1 group （RvD1 10 ng/ml ＋ LPS 5 μg/ml）, and blockage group （Boc-MLP 10 ng/ml ＋ RvD1 10 ng/ml ＋ LPS 5 μg/ml）. The cells were harvested for RNA at 2, 4, 6, 12, and 24 h time points, respectively （n = 6 in each group at each time point）. Blood creatinine was tested by using an Abbott i-STAT portable blood gas analyzer. Tumor necrosis factor-α （TNF-α level was detected by EL1SA. Kidney pathology was observed under hematoxylin and eosin （HE） staining and transmission electron microscope （TEM）. We hired immune-histological staining, Western blotting, and fluorescence quantitative polymerase chain reaction to detect the expression of RvD1 receptor ALX, nuclear factor-kappa B （NF-KB） signaling pathway as well as caspase-3. Kidney apoptosis was evaluated by TUNEL staining. Results： RvD 1 receptor ALX was detected on renal tubular epithelials. Kaplan-Meier analysis indicated that RvD 1 improved 48 h animal survival （80%） compared with LPS group （40%） and RvDI blockage group （60%）, while RvD1 also ameliorated kidney pathological injury in HE staining and TEM scan. After LPS stimulation, the mRNA expression of toll-like receptor 4, myeloid differentiation factor 88, and TNF-α in both mice kidneys and HK-2 cells were all up-regulated, while RvDI substantially inhibited the up-regulation of these genes. Western blotting showed that the phosphorylated-IKB/IKB ratio in LPS group was significantly higher than that in the control group, which was inhibited in the RvD1 group. RvD1 could inhibit the up-regulation of cleaved-caspase-3 protein stimulated by LPS, which was prohibited in RvD 1 blockage group. RvD 1 group also had a lower proportion of apoptotic nuclei in mice kidney by TUNEL staining compared with LPS group. Conclusion： In LPS-induced AKI, RvD1 could decrease TNF-α level, ameliorate kidney pathological injury, protect kidney function, and improve animal survival by down-regulating NF-KB inflammatory signal as well as inhibiting renal cell apoptosis.

Influence of HbA1c on short-term blood pressure variability in type 2 diabetic patients with diabetic nephropathy

The aim of this study was to understand the characteristics of blood pressure(BP)variability in subjects with diabetic nephropathy(DN),and identify the probable predictors affecting BP variability.Fifty-one chronic kidney disease(CKD)-hypertensive patients without diabetes(NDN group)and sixty type 2 diabetic patients with overt DN(DN group)were enrolled in this study.The values of short-term BP variability were obtained from 24 h ambulatory BP monitoring(ABPM).Variance analysis or nonparametric analysis revealed that 24-h systolic BP variability and nighttime systolic BP variability of the DN group were significantly higher than those of the NDN group[(12.23±3.66)vs.(10.74±3.83)mmHg,P<0.05;(11.23±4.82)vs.(9.48±3.69)mmHg,P<0.05].Then the patients of the DN group were divided into two groups according to glycated hemoglobin(HbA1c)level:Group A(HbA1c<7%)and Group B(HbA1c≥7%),and the t-test showed that patients in Group B had larger 24-h diastolic,daytime diastolic,and nighttime systolic/diastolic BP variability compared with Group A.In the DN group,partial correlation analysis revealed that HbA1c exhibited a strong association with 24-h diastolic,daytime diastolic,nighttime systolic and diastolic BP variability(P<0.001,P<0.001,P<0.05,and P<0.001,respectively).Taken together,larger short-term BP variability was detected in hypertensive type 2 diabetic patients with overt nephropathy and renal insufficiency.It may imply that the optimal BP variability level could benefit from a better glycaemic control.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients： Subgroup Meta-analysis

Background： Catheter-based renal denervation （RDN） is a novel treatment tbr resistant hypertension （RH）. A recent meta-analysis reported that RDN did not significantly reduce blood pressure （BP） based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. Methods： This was a meta-analysis of 9 randomized clinical trials （RCTs） among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure （SBP） level, antihypertensive medication change rates, and coronary heart disease （CHD）. Results： In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-11 SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP 〉 155 mmHg （ 1 mmHg = 0.133 kPa） and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months （P = 0.100 and P = 0.009, respectively）. Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months （P 〈 0.001 ）. Conclusions： In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBR