Search

Purpose This study aimed to explore the relationship between serum magnesium (Mg) levels and incidence of acute kidney injury (AKI) in patients with malignancy. Patients and methods Hospitalized patients with malignancy between October 1, 2014 and September 30, 2015 in Zhongshan Hospital were recruited. All relevant data were extracted from the electronic database. Results All 99,845 patients were enrolled and 16,082 eligible patients were divided into three groups according to admission serum Mg levels in this study. Among them, 2383 (14.8%) cases were diagnosed as AKI. The incidence of AKI showed a V trend with the increase of serum Mg level. The effect of low serum Mg level on the onset of AKI seems to be greater than high serum Mg level. Patients with low serum Mg level spent a longer time in the hospital than those with normal serum Mg level and high serum Mg level. Further, multivariate logistic regression model was used to assess the importance of serum Mg level to influence AKI incidence. There was a higher AKI incidence in patients with magnesium level 0.66mmol/L or less (aOR=2.438, 95% CI=1.696, 3.505). Conclusion Low serum Mg level might be a independent risk factor for AKI in patients with malignancy. Appropriate clinical intervention for serum Mg disorder may contribute to decreasing the incidence of AKI and the possibility of poor outcomes in cancer patients.

Electrolyte and acid-base disorders are commonly seen in critically ill and other hospitalized patients. A scoring system is needed to assess the severity of electrolyte and acid-base disorders and to predict outcome in hospital patients. Herein, we prospectively enrolled a total of 322,046 patients, including 84,700 patients in the derivation cohort and 237,346 in the validation cohort, in a large, tertiary hospital in East China from 2014 to 2017. A points-scoring system of general electrolyte and acid-base disorders with a sum of 20.8 points was generated by multiple logistic regression analysis of the derivation cohort. Receiver operating characteristic curve analysis showed that the optimal cut-off value of 2.0 was associated with 65.4% sensitivity and 88.4% specificity (area under the curve: 0.818 (95% CI 0.809 to 0.827)) to predict hospital mortality in the validation cohort. On Kaplan-Meier survival analysis, the five intervals of risk score (Q1: 0 to 2.0; Q2: 2.1 to 2.5; Q3: 2.6 to 3.3; Q4: 3.4 to 4.5; and Q5: >4.5 points) showed differences in hospital survival (p2 during hospitalization increased the risk of hospital death, while those with a delta risk score

Small noncoding RNAs (sncRNAs) are important regulators of gene expression. In contrast with well-studied microRNAs, transfer RNA-derived RNA fragments (tRFs) are a new class of sncRNAs that has not been studied in hypertension. This study aims to characterize renal tRFs and identify dysregulation and potential role of renal tRFs in hypertension. We analyzed sncRNA-sequencing and mRNA-sequencing data from the kidneys of Dahl salt-sensitive rats and sncRNA-sequencing data from kidney biopsy specimens from hypertensive nephrosclerosis patients. Over 300 tRFs were identified in the rat renal outer medulla, several of which were differentially expressed between rats with different levels of salt sensitivity or between rats on low- and high-salt diets. The number and abundance of these tRFs were comparable with those of well-known microRNAs. Multiple tRFs were potentially involved in the regulation of immune function, cell cycle, ion transport, and metabolic pathways based on an integrative analysis of sncRNA-sequencing and mRNA-sequencing data from the same set of rats. As a proof of concept, we experimentally validated the gene regulatory effect of a 3′-tRF (3′-tRF-ProTGG-19) that was dysregulated in both salt-induced hypertension in rats ( P =0.002) and hypertensive nephrosclerosis in humans ( P =1.7×10 −05 ). To our knowledge, our study represents the first characterization of tRFs in hypertension. These findings demonstrate the abundant expression of tRFs in human and rat kidneys and pave the way for studies to investigate novel roles of renal tRFs in the development of hypertension and renal injury.

INTRODUCTION Intradialytic hypotension (IDH) is a common complication in end-stage renal disease patients on hemodialysis (HD). It has been documented that several factors contribute to IDH. However, the relationship between serum electrolytes and the occurrence of IDH remains unclear. Our study aims to investigate the role of serum magnesium (Mg) for the risk of IDH in maintenance HD patients. METHODS The retrospective study included adults starting HD before January 2009 in the blood purification center, Zhongshan Hospital, Fudan University, and treated thrice weekly with standard bicarbonate dialysate by low-flux HD. Patients' characteristics including age and sex, laboratory test results were collected. IDH was defined according to kidney disease outcomes quality initiative (K/DOQI) guidelines as a decrease in systolic blood pressure (SBP) by ≥20 mmHg or a decrease in mean arterial pressure (MAP) by ≥10 mmHg associated with clinical symptoms during HD. Multivariate logistic regression was employed to explore independent risk factors for IDH. FINDINGS Among 423 patients recruited, 175 patients (41.4%) suffered from IDH. Compared with those with non-IDH, patients with IDH presented higher predialysis serum Mg levels. Univariate correlation analysis showed that predialysis serum Mg level was negatively correlated with SBP at 3 hours, 4 hours after dialysis (3 hours SBP r = -0.134 P = 0.006, 4 hours SBP r = -0.142 P = 0.003) and was positively correlated with the differences of blood pressure (BP) (SBP and MAP) (△SBP r = 0.195 P

Metabolic acidosis has been proved to be a risk factor for the progression of chronic kidney disease, but its relation to acute kidney injury (AKI) has not been investigated. In general, a diagnosis of metabolic acidosis is based on arterial blood gas (ABG) analysis, but the diagnostic role of carbon dioxide combining power (CO2CP) in the venous blood may also be valuable to non-respiratory patients. This retrospective study included all adult non-respiratory patients admitted consecutively to our hospital between October 01, 2014 and September 30, 2015. A total of 71,089 non-respiratory patients were included, and only 4,873 patients were evaluated by ABG analysis at admission. In patients with ABG, acidosis, metabolic acidosis, decreased HCO3− and hypocapnia at admission was associated with the development of AKI, while acidosis and hypocapnia were independent predictors of hospital mortality. Among non-respiratory patients, decreased CO2CP at admission was an independent risk factor for AKI and hospital mortality. ROC curves indicated that CO2CP was a reasonable biomarker to exclude metabolic acidosis, dual and triple acid-base disturbances. The effect sizes of decreased CO2CP on AKI and hospital mortality varied according to age and different underlying diseases. Metabolic acidosis is an independent risk factor for the development of AKI and hospital mortality. In non-respiratory patient, decreased CO2CP is also an independent contributor to AKI and mortality and can be used as an indicator of metabolic acidosis.

Background: Mounting evidence has indicated that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) played an important role in renal ischemia/reperfusion (I/R) injury. However, the involvement of lncRNA growth arrest specific transcripts 5 (GAS5) in acute kidney injury (AKI) remained largely unexplored. This study aimed to determine the functions of GAS5 and possible molecular mechanisms during the renal I/R process. Methods: Bioinformatic analysis revealed possible interaction involving GAS5, miR-21 and thrombospondin 1(TSP-1). Dural Luciferase reporter assays were employed to identify the regulatory relationship between GAS5 and miR-21 as well as between miR-21 and TSP-1. In this study, renal I/R and delayed IPC models were established in vivo. Besides, hypoxia/reoxygenation for different time (H6R0.5 and H24R3) was induced in vitro. Then we performed real-time PCR, western blot, flow cytometry, TUNEL assay to explore possible downstream regulatory molecules. LNA modified anti-miR-21 and anti-scramble were delivered intraperitoneally 1h before procedure or transfected into HK-2 cells to knock down the expression of miR-21. Also, small interfering RNA and plasmids were used to knock down and overexpress the level of GAS5 in HK-2 cells, respectively. Findings: GAS5, noticeably upregulated by renal I/R injury, was further suppressed by delayed IPC while knockdown of miR-21 in vivo before IPC could significantly increased the expression of GAS5. Concurrently, TSP-1 was negatively regulated by miR-21 in vivo and vitro. Additionally, Reciprocal repression of GAS5 and miR-21 was identified. Knockdown of miR-21 in H6R0.5 treated HK-2 cells promoted apoptosis. Co-transfection of miR-21 mimic and pcDNA-GAS5 or pcDNA-Vector were performed, results of which showed that co-transfection of inhibition of miR-21 on TSP-1 could be rescued by overexpression of GAS5. Interpretation: GAS5 facilitated the apoptosis by competitively sponging miR-21, which negatively regulated TSP-1 in renal I/R injury. This novel regulatory axis could act as a therapeutic target for AKI in the future. Funding Statement: National Natural Science Foundation of China grants 81770734 (to Dr. Xu) and 81430015 (to Dr. Ding); Science and Technology Commission of Shanghai (14DZ2260200) and Construction Project of Shanghai Renal Disease Clinical Medical Center (2017ZZ01015). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All protocols were approved by Institutional Animal Care Use Committee of Fudan University.

Aim Long non-coding RNA (lncRNAs) have been shown to play a critical role in a variety of pathophysiological processes, such as cell proliferation, apoptosis and migration. However, there were few studies addressing the function of lncRNAs in renal ischaemia/reperfusion (I/R) injury. Apoptosis is an important pathogenesis during I/R injury. Here, we identified the effect of hypoxia-responsive lncRNA growth arrest-specific 5 (GAS5) on apoptosis in renal I/R injury. Methods Ischaemia/reperfusion injury in mice or hypoxia/re-oxygenation (H/R) in human proximal renal tubular epithelial cells (HK-2) was practiced to induce apoptosis. The kidneys and blood were collected at 24 h after reperfusion. The GAS5 messenger RNA (mRNA) expression and apoptosis-related gene mRNA and protein levels, including p53, cellular inhibitor of apoptosis protein 2 (cIAP2) and thrombospondin-1 (TSP-1), were analysed. GAS5 small-interfering RNA was transfected with H/R induced cells. Over-expression of GAS5 was performed by plasmid transfection. Results Apoptotic cells significantly increased in I/R-injured kidneys. GAS5 could be up-regulated in kidneys at 24 h after reperfusion and 3 h after re-oxygenation, combined with increased expression of its downstream apoptosis-related proteins p53 and cIAP2. GAS5 small-interfering RNA treatment down-regulated the mRNA and protein levels of p53 and TSP-1, and attenuated apoptosis induced by H/R in HK-2 cells. Conversely, over-expression of GAS5 up-regulated the mRNA and protein levels of p53 and TSP-1, and promoted apoptosis in HK-2 cells. Conclusion Long non-coding RNA GAS5 induced by I/R injury could promote apoptosis in kidney. TSP-1 might be one of the downstream effectors of GAS5, which will be explored in the future.

Recent studies suggest that the AMP-activated protein kinase (AMPK) acts as a major energy sensor and regulator in adipose tissues. The objective of this study was to investigate the role of AMPK in nicotine-induced lipogenesis and lipolysis in 3T3L1 adipocytes. Exposure of 3T3L1 adipocytes to smoking-related concentrations of nicotine increased lipolysis and inhibited fatty acid synthase (FAS) activity in a time- and dose-dependent manner. The effects of nicotine on FAS activity were accompanied by phosphorylation of both AMPK (Thr172) and acetyl-CoA carboxylase (ACC; Ser79). Nicotine-induced AMPK phosphorylation appeared to be mediated by reactive oxygen species based on the finding that nicotine significantly increased superoxide anions and 3-nitrotyrosine-positive proteins, exogenous peroxynitrite (ONOO–) mimicked the effects of nicotine on AMPK, and N-acetylcysteine (NAC) abolished nicotine-enhanced AMPK phosphorylation. Inhibition of AMPK using either pharmacologic (insulin, compound C) or genetic means (overexpression of dominant negative AMPK; AMPK-DN) abolished FAS inhibition induced by nicotine or ONOO–. Conversely, activation of AMPK by pharmacologic (nicotine, ONOO–, metformin, and AICAR) or genetic (overexpression of constitutively active AMPK) means inhibited FAS activity. Notably, AMPK activation increased threonine phosphorylation of FAS, and this effect was blocked by adenovirus encoding dominant negative AMPK. Finally, AMPK-dependent FAS phosphorylation was confirmed by 32P incorporation into FAS in adipocytes. Taken together, our results strongly suggest that nicotine, via ONOO– activates AMPK, resulting in enhanced threonine phosphorylation and consequent inhibition of FAS.