Chaojun Qi

Diagnostic Value of Urinary Kidney Injury Molecule 1 for Acute Kidney Injury: A Meta-Analysis

Background Urinary Kidney Injury Molecule 1 (KIM-1) is a proximal tubular injury biomarker for early detection of acute kidney injury (AKI), with variable performance characteristics depending on clinical and population settings. Methods Meta-analysis was performed to assess the diagnostic value of urinary KIM-1 in AKI. Relevant studies were searched from MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar and Cochrane Library. Meta-analysis methods were used to pool sensitivity and specificity and to construct summary receiver operating characteristic (SROC) curves. Results A total of 2979 patients from 11 eligible studies were enrolled in the analysis. Five prospective cohorts, two cross-sectional and four case-control studies were identified for meta-analysis. The estimated sensitivity of urinary KIM-1 for the diagnosis of AKI was 74.0% (95% CI, 61.0%–84.0%), and specificity was 86.0% (95% CI, 74.0%–93.0%). The SROC analysis showed an area under the curve of 0.86(0.83–0.89). Subgroup analysis suggested that population settings and detection time were the key factors affecting the efficiency of KIM-1 for AKI diagnosis. Limitation Various population settings, different definition of AKI and Serum creatinine level used as the standard might have influence on AKI diagnosis. The relatively small number of studies and heterogeneity between them also affected the evaluation. Conclusion Urinary KIM-1 may be a promising biomarker for early detection of AKI with considerable predictive value, especially for cardiac surgery patients, and its potential value needs to be validated in large studies and across a broader scope of clinical settings.

Up-regulation of Serum MiR-130b-3p Level is Associated with Renal Damage in Early Lupus Nephritis

Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic inflammatory disease. Lupus nephritis (LN) is a serious complication of SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are emerging as biomarkers for pathological conditions and play significant roles in intercellular communication. In present research, serum samples from healthy control, early and late stage LN patients were used to analyze the expression profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p in serum of patients with early stage LN were significantly up-regulated when compared with healthy controls. In addition,we have also observed that the expression of a large amount of circulating microRNAs significantly decreased in patients with late stage LN. The further analysis found that the expression of serum miR-130b-3p was positively correlated with 24-hour proteinuria and renal chronicity index in patients with early stage LN.Transfection of renal tubular cellline(HK-2)with miR-130b-3p mimics can promote epithelial-mesenchymal transition (EMT). The opposite effects were observed when transfected with miR-130b-3p inhibitors. MiR-130b-3p negatively regulated ERBB2IP expression by directly targeting the 3′-UTR of ERBB2IP The circulating miR-130b-3p might serve as a biomarker and play an important role in renal damage in early stage LN patients.

NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis

Iodinated contrast media serves as a direct causative factor of acute kidney injury (AKI) and is involved in the progression of cellular dysfunction and apoptosis. Emerging evidence indicates that NLRP3 inflammasome triggers inflammation, apoptosis and tissue injury during AKI. Nevertheless, the underlying renoprotection mechanism of NLRP3 inflammasome against contrast-induced AKI (CI-AKI) was still uncertain. This study investigated the role of NLRP3 inflammasome in CI-AKI both in vitro and in vivo. In HK-2 cells and unilateral nephrectomy model, NLRP3 and NLRP3 inflammasome member ASC were significantly augmented with the treatment of contrast media. Moreover, genetic disruption of NLRP3 notably reversed contrast-induced expression of apoptosis related proteins and secretion of proinflammatory factors, similarly to the effects of ASC deletion. Consistent with above results, absence of NLRP3 in mice undergoing unilateral nephrectomy also protected against contrast media-induced renal cells phenotypic alteration and cell apoptosis via modulating expression level of apoptotic proteins. Collectively, we demonstrated that NLRP3 inflammasome mediated CI-AKI through modulating the apoptotic pathway, which provided a potential therapeutic target for the treatment of contrast media induced acute kidney injury.

Astragalosides IV inhibits high glucose-induced cell apoptosis through HGF activation in cultured human tubular epithelial cells

Abstract Astragaloside IV (ASI) in Radix Astragali is believed to be the active component. The study aims to investigate whether ASI inhibits tubular epithelial cells apoptosis induced by high glucose and its mechanisms. Tubular epithelial cells in this paper were isolated from human kidney. The cells apoptosis was detected by TUNEL and caspase 3 assay. The protein levels of HGF and TGF-β1 were measured by ELISA. The phospho-p38 production, ERK and JNK were determined by Western blot. ASI could inhibit cells apoptosis induced by high glucose (25 mmol/L) in dose-dependent and time-dependent manners. ASI also inhibited high glucose-induced expression of TGF-β1 and activation of p38 MAPK pathway at the protein level. Furthermore, ASI increased HGF production in human tubular epithelial cells. The ASI inhibition of tubular epithelial cells apoptosis and reduction of TGF-β1 expression induced by high glucose may represent a new treatment for diabetic kidney injury. The mechanism underlying this inhibitory effect may be related to the inhibition of p38 MAPK signaling pathway activation and HGF overproduction.

Metabolic Syndrome Is Correlated With Carotid Atherosclerosis in Patients With Lupus Nephritis

Background:To investigate the prevalence of metabolic syndrome (MS) in patients with lupus nephritis (LN), and its correlation with carotid atherosclerosis. Methods:Two hundred ten patients with LN (age: 38.83 ± 12.41 years, 92.86% women) were enrolled. The control group included 150 lupus patients without nephritis and 200 age-matched healthy persons. The improved criteria in 2009 were used to calculate the prevalence of MS, and carotid artery ultrasound was used to detect plaque and intima-media thickness (IMT). The correlation between MS and carotid atherosclerosis in patients with LN was analyzed. Results:The prevalence of MS in patients with LN was 41.90%, which was significantly higher than that in lupus patients without nephritis (30.67%) and healthy controls (11.50%). LN patients with MS showed a significantly increased carotid plaque ratio (28.41% versus 17.21%, P < 0.05) and IMT value (0.74 ± 0.25 mm versus 0.64 ± 0.18 mm, P < 0.01). Stepwise multiple regression further confirmed that age (&bgr; = 0.026, P = 0.033), duration of disease (&bgr; = 0.057, P = 0.025) and MS (&bgr; = 0.074, P < 0.001) were independent risk factors that affected the carotid IMT value in patients with LN. Conclusions:The prevalence of MS was comparatively high in patients with LN and was significantly correlated with carotid atherosclerosis, indicating that MS screening might be useful in the prevention and treatment of carotid atherosclerosis in patients with LN.

Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis

Introduction Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN. Methods For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity–2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry. Results Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages. Conclusion Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an important role in disease progression of LN.

Serum sclerostin level might be a potential biomarker for arterial stiffness in prevalent hemodialysis patients

AIM To explore the relationship between circulating sclerostin levels and pulse wave velocity (PWV) in prevalent hemodialysis (HD) patients. PATIENTS & METHODS 154 HD patients were enrolled and examined for serum sclerostin level, carotid-femoral pulse wave velocity (cf-PWV), abdominal artery calcification and calcaneus bone marrow density. RESULTS Serum sclerostin level was significantly elevated in patients with arterial stiffness. Univariate correlation showed serum sclerostin level significantly correlated with intact parathyroid hormone level, cf-PWV and calcaneus bone marrow density. Multiple linear regression analysis in patients with parathyroid hormone ≤300 pg/ml showed that pulse pressure, logAACs and serum sclerostin level were significant independent factors for cf-PWV. CONCLUSION Serum sclerostin level was significantly associated with PWV in prevalent HD patients without hyperparathyroidism.

Possible role of IL-6 and TIE2 gene polymorphisms in predicting the initial high transport status in patients with peritoneal dialysis: an observational study

Objectives The aim of this study was to investigate the effect of interleukin (IL)-6 and TIE2 gene polymorphisms on baseline peritoneal transport property. Design An observational study. Setting Renji Hospital in Shanghai, China. Participants This study included 220 patients with continuous ambulatory peritoneal dialysis (PD). Outcome measures Patients were divided into 2 groups based on the results of an initial peritoneal equilibration test performed within 3 months of starting PD therapy: group 1 consisted of low/low average transporters (n=123), and group 2 consisted of high/high average transporters (n=97). We genotyped TIE2 and IL-6 polymorphisms and analysed their effects on baseline transport status. Results The genotype AT in IL-6 Rs13306435 and the genotype CC in TIE2 Rs639225 were both negatively associated with a higher initial peritoneal transport status (IL-6 Rs13306435: OR=0.408, 95% CI 0.227 to 0.736; TIE2 Rs639225: OR=0.188, 95% CI 0.044 to 0.806). Conclusions IL-6 and TIE2 polymorphisms are associated with baseline peritoneal transport property.

Blood HCO3 - concentration predicts the long-term prognosis of acute kidney injury patients

AIM To evaluate the value of HCO3(-) concentrations in long-term prognosis after acute kidney injury. PATIENTS & METHODS A total of 169 AKI patients were included in this study. At the 12-month follow-up, the patients were divided into recovered and unrecovered groups. RESULTS The blood HCO3(-) concentrations were significantly correlated with poor prognosis. The area under the curve for renal prognosis of 6 months later blood HCO3(-) concentrations was 0.798. Combined HCO3(-) and Scr level area under the curve was 0.952. CONCLUSION The blood HCO3(-) level was useful in evaluating renal prognosis of acute kidney injury patients. The combination of blood HCO3(-) concentration and Scr level increased the accuracy of prediction.

Association of Relapse with Renal Outcomes under the Current Therapy Regimen for IgA Nephropathy: A Multi-Center Study.

Background and Objectives Renal relapse is a very common manifestation of IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored. Design and Patients Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study. Results Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5%) of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4%) in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6%) in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP) was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling on the validation cohort. Conclusions This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse.