Background
Multi-organ dysfunction in critical illness is common and frequently involves the lungs and kidneys, often requiring organ support such as invasive mechanical ventilation (IMV), renal ...replacement therapy (RRT) and/or extracorporeal membrane oxygenation (ECMO).
Methods
A consensus conference on the spectrum of lung–kidney interactions in critical illness was held under the auspices of the Acute Disease Quality Initiative (ADQI) in Innsbruck, Austria, in June 2018. Through review and critical appraisal of the available evidence, the current state of research, and both clinical and research recommendations were described on the following topics: epidemiology, pathophysiology and strategies to mitigate pulmonary dysfunction among patients with acute kidney injury and/or kidney dysfunction among patients with acute respiratory failure/acute respiratory distress syndrome. Furthermore, emphasis was put on patients receiving organ support (RRT, IMV and/or ECMO) and its impact on lung and kidney function.
Conclusion
The ADQI 21 conference found significant knowledge gaps about organ crosstalk between lung and kidney and its relevance for critically ill patients. Lung protective ventilation, conservative fluid management and early recognition and treatment of pulmonary infections were the only clinical recommendations with higher quality of evidence. Recommendations for research were formulated, targeting lung–kidney interactions to improve care processes and outcomes in critical illness.
The human miR-29 family of microRNAs has three mature members, miR-29a, miR-29b, and miR-29c. miR-29s are encoded by two gene clusters. Binding sites for several transcriptional factors have been ...identified in the promoter regions of miR-29 genes. The miR-29 family members share a common seed region sequence and are predicted to target largely overlapping sets of genes. However, the miR-29 family members exhibit differential regulation in several cases and different subcellular distribution, suggesting their functional relevance may not be identical. miR-29s directly target at least 16 extracellular matrix genes, providing a dramatic example of a single microRNA targeting a large group of functionally related genes. Strong antifibrotic effects of miR-29s have been demonstrated in heart, kidney, and other organs. miR-29s have also been shown to be proapoptotic and involved in the regulation of cell differentiation. It remains to be explored how various cellular effects of miR-29s determine functional relevance of miR-29s to specific diseases and how the miR-29 family members may function cooperatively or separately.
A risk assessment method for hot work based on G1-EWM and unascertained measurement theory was proposed to prevent hot work accidents in underground mines. Firstly, based on the risk influencing ...factors and classification criteria for underground hot work operations in mines, a single indicator measurement matrix was constructed using unascertained measurement theory; Secondly, a risk assessment index system for mine underground hot work operations was established. The combination weight coefficient of each index was determined using the order relationship analysis method (G1) and entropy weight method (EWM) and coupled with the single index measurement evaluation vector to calculate the multi-index comprehensive evaluation vector of the evaluation object; Finally, the model was validated and examined using engineering examples, and the evaluation level was determined using confidence identification criteria. The results showed that the proposed method, when used to evaluate the risk of hot work operations in tunnels and vertical shafts in metal mines, produces risk levels that are in line with reality III (Moderate Risk) for the vertical shaft and IV (High Risk) for the tunnels. The evaluation model results are consistent with the risk evaluation results the whole process of on-site hot work, which verifies the model feasibility. A unique strategy and method for risk management in hot work operations in underground mines is provided by the combination of weighting and unascertained measure models, which has theoretical and practical value. Future research could focus on refineing this model by exploring the applicability in diverse mining environments and integrating advanced analytical techniques to enhance the predictive accuracy and operational efficiency.
Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there ...has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled “Early Identification and Intervention in CKD.” Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.
Acute kidney injury (AKI) has a critical role in the development of chronic kidney disease (CKD). Building on our previous findings, we explored the role of miR-382 in facilitating the transition of ...AKI to CKD using the Aristolochic acid (AA) nephropathy model, which was induced by intraperitoneal injection of aristolochic acid I salt (10 or 20 mg/kg). The effects of genetic depletion, pharmacologic inhibition, or overexpression of miR-382 on the PTEN/AKT signaling pathway were examined in vivo and in vitro. Changes in renal pathology and renal epithelial polarity were evaluated. A luciferase reporter assay was performed to investigate the reciprocal suppression relationship between miR-382 and PTEN. Renal fibrosis developed 14 d after AA exposure in a dose- and time-dependent manner. Renal abundance of miR-382 was upregulated following AA treatment, while genetic depletion or pharmacological inhibition of miR-382 partially reversed renal tubulointerstitial fibrosis. Expression of PTEN, a target of miR-382, was downregulated and subsequently its downstream AKT signaling pathway was activated during AKI to CKD transition induced by AA. Inhibition of PTEN in vitro resulted in the acquisition of the EMT phenotypes. Furthermore, upregulation of miR-382 in renal epithelial cells was partially mediated by the activation of NF-kB signaling, with a substantial elevation of proinflammatory cytokines. An in vivo study revealed that either miR-382 knockdown or miR-382 knockout was pivotal for inflammatory suppression, while an in vitro experiment confirmed that upregulation of miR-382 in cultured MTEC cells under AA exposure was remarkably reversed by NF-kB siRNA. These data indicated a novel role for the NF-κB/miR-382/PTEN/AKT axis in the pathogenesis of tubulointerstitial fibrosis following AA-induced acute renal tubular epithelial injury. Targeting miR-382 may lead to a potential novel therapeutic approach for retarding the AKT to CKD transition.
Purpose: To investigate the potential of diffusion kurtosis imaging (DKI) for the assessment of renal fibrosis in chronic kidney disease (CKD), using histopathology as the reference standard.
...Methods: Eighty-nine CKD patients and twenty healthy volunteers were recruited in this study. DKI was performed in all participants and all CKD patients received renal biopsy. The values of mean diffusivity (MD) and mean kurtosis (MK) in the renal cortex and medulla were compared between CKD patients and healthy volunteers. The Spearman correlation coefficient was calculated to assess the relationship between MD, MK values and the estimated glomerular filtration rate (eGFR), serum creatinine (SCr), 24 h urinary protein (24 h-UPRO), histopathological fibrosis score.
Results: The medullary MD values were significantly lower than cortex, while the cortical MK values were significantly lower than medulla for all participants. Renal parenchymal MD values were significantly lower in the CKD patients than healthy controls, whereas MK values were significantly higher in the CKD patients than healthy controls. In the CKD patients, the significantly negative correlation was observed between the renal parenchymal MD values and the 24 h-UPRO, SCr, histopathological fibrosis score, as well as between the renal parenchymal MK values and the eGFR, while the significantly positive correlation was found between the renal parenchymal MD values and the eGFR, as well as between the renal parenchymal MK values and the 24 h-UPRO, SCr, histopathological fibrosis score.
Conclusion: DKI shows great potential in the noninvasive assessment of renal fibrosis in CKD.
Abstract
Background
Epithelial-mesenchymal transition (EMT) of mesothelial cells is a key step in the peritoneal fibrosis (PF). Recent evidence indicates that signal transducer and activator of ...transcription 3 (STAT3) might mediate the process of renal fibrosis, which could induce the expression of hypoxia-inducible factor-1α (HIF-1α). Here, we investigated the effect of STAT3 activation on HIF-1α expression and the EMT of mesothelial cells, furthermore the role of pharmacological blockade of STAT3 in the process of PF during peritoneal dialysis (PD) treatment.
Methods
Firstly, we investigated the STAT3 signaling in human peritoneal mesothelial cells (HPMCs) from drained PD effluent. Secondly, we explored the effect of STAT3 signaling activation on the EMT and the expression of HIF-1α in human mesothelial cells (Met-5A) induced by high glucose. Finally, peritoneal fibrosis was induced by daily intraperitoneal injection with peritoneal dialysis fluid (PDF) so as to explore the role of pharmacological blockade of STAT3 in this process.
Results
Compared with the new PD patient, the level of phosphorylated STAT3 was up-regulated in peritoneal mesothelial cells from long-term PD patients. High glucose (60 mmol/L) induced over-expression of Collagen I, Fibronectin, α-SMA and reduced the expression of E-cadherin in Met-5A cells, which could be abrogated by STAT3 inhibitor S3I-201 pretreatment as well as by siRNA for STAT3. Furthermore, high glucose-mediated STAT3 activation in mesothelial cells induced the expression of HIF-1α and the profibrotic effect of STAT3 signaling was alleviated by siRNA for HIF-1α. Daily intraperitoneal injection of high-glucose based dialysis fluid (HG-PDF) induced peritoneal fibrosis in the mice, accompanied by the phosphorylation of STAT3. Immunostaining showed that phosphorylated STAT3 was expressed mostly in α-SMA positive cells in the peritoneal membrane induced by HG-PDF. Administration of S3I-201 prevented the progression of peritoneal fibrosis, angiogenesis, macrophage infiltration as well as the expression of HIF-1α in the peritoneal membrane induced by high glucose.
Conclusions
Taken together, these findings identified a novel mechanism linking STAT3/HIF-1α signaling to peritoneal fibrosis during long-term PD treatment. It provided the first evidence that pharmacological inhibition of STAT3 signaling attenuated high glucose-mediated mesothelial cells EMT as well as peritoneal fibrosis.
OBJECTIVE:Sepsis, triggered by microbial infection, is a common and life-threatening systemic illness, often leads to impaired function of vital organs. Ischemic preconditioning induced by transient ...brief episodes of ischemia is a powerful innate mechanism of organ protection. We have reported that a 15-minute renal ischemic preconditioning substantially attenuated subsequent renal ischemia-reperfusion injury. Here, we investigate whether a brief ischemia and reperfusion in kidney can provide protection at local and remote sites against sepsis-induced organ injury, and whether this protection is microRNA-21 dependent.
DESIGN:Laboratory study.
SETTING:University laboratory.
SUBJECTS:Mouse renal tubular epithelial cells, C57BL/6 J wildtype (Animal Center of Fudan University, Shanghai, China) and microRNA-21–/– mice (B6.129-Mir21atm1Smoc, Shanghai Biomodel Organism Science & Technology Development Co. Shanghai, China).
INTERVENTIONS:Mouse renal tubular epithelial cells were treated with hypoxia (2% oxygen). Renal ischemic preconditioning was induced by bilateral renal pedicle clamping for 15 minutes, and sepsis was induced by a single intraperitoneal injection of lipopolysaccharide at a dose of 20 mg/kg or cecal ligation and puncture in mice.
MEASUREMENTS AND MAIN RESULTS:Mice treated with renal ischemic preconditioning were protected from endotoxemia or polymicrobial sepsis-induced multiple organ injury, including kidneys, heart, liver, and lungs. Renal ischemic preconditioning induced activation of hypoxia-inducible factor-1α in kidneys, which up-regulated microRNA-21 at transcriptional level, subsequently, leading to increased expression of microRNA-21 in serum exosomes and remote organs, resulting in decreased apoptosis and reduced proinflammatory cytokines production in these organs. In vivo knockdown of microRNA-21 or genetic deletion of microRNA-21 abrogated the organoprotective effects conferred by renal ischemic preconditioning. Mechanistically, we discovered that knockdown of microRNA-21 increased programmed cell death protein 4 expression and nuclear factor-kappa B activity, decreased expression of anti-apoptotic B-cell lymphoma-2.
CONCLUSION:MicroRNA-21 is required for local and remote ischemic preconditioning in multiple organ protection against sepsis, and up-regulation of miR-21 may be a potential therapy for sepsis.
Renal tubule-interstitial fibrosis is related to chronic kidney disease progression and a typical feature of the aging kidney. Epigenetic modifications of fibrosis-prone genes regulate the ...development of renal fibrosis. As a kind of "epigenetic diet", soy isoflavone genistein was reported to have renal protective action and epigenetic-modulating effects. However, its renal protection role and underlying mechanisms are yet to be fully clarified. Herein, we showed that genistein exhibits a demonstrable anti-fibrotic effect on kidney
UUO (unilateral ureteral occlusion) model and renal epithelial cells
model. The mechanism is strongly associated with epithelial-to-mesenchymal transition and m6A RNA demethylase ALKBH5. Mouse fibrotic kidneys induced by UUO exhibited adverse expression of renal fibrosis-related proteins and significant increases in the total m6A level. As an eraser, ALKBH5 showed severer suppression in the renal fibrosis process. However, genistein pretreatment restored ALKBH5 loss remarkably and reduced renal fibrosis, abnormal protein, and inflammatory markers. The examination of possible mechanisms revealed that genistein promoted ALKBH5 and maybe induced the level of mRNA m6A methylation in some epithelial-to-mesenchymal transition-related transcription factors. We found snail was the critical regulator and critical for the protective role of genistein. To verify the relationship between ALKBH5 and snail, we generated knockdown and overexpression of ALKBH5 cells
. ALKBH5 knockdown enhanced the mesenchymal phenotype marker α-smooth muscle actin and snail expression. In agreement, overexpression ALKBH5 increased epithelial adhesion molecule E-cadherin and reduced snail expression. In conclusion, genistein increased renal ALKBH5 expression in UUO-induced renal fibrosis and reduced RNA m6A levels and ameliorates renal damages.
Hyperuricemia (HUA) is becoming a global public health problem and associated with multiple diseases.
We conducted a systematic review to synthesize the pooled prevalence of HUA in mainland China and ...delineate its demographic, regional, and temporal trends over the past two decades.
Systematic literature searches of PubMed, SCOPUS, Web of Science, the China National Knowledge Infrastructure (CNKI), and the Wanfang digital database were conducted to screen studies published from 1 January 2000 to 31 August 2019, reporting the prevalence of HUA in mainland China. The search strings were ('hyperuricemia' OR 'hyperuricaemia' OR 'uric acid') AND ('prevalence' OR 'epidemiology') AND 'China'. Article quality was appraised quantitatively from 11 items. Before formal meta-analysis, age-standardized prevalence was transformed. The random-effects model was applied to synthesize the pooled prevalence due to its high heterogeneity. Then we stratified the prevalence estimates by age, gender, area, nationality, and publication year for subgroup analysis.
Totally 177 eligible studies with a whole population of 2,277,712 were included in the present meta-analysis. The pooled prevalence in mainland China was estimated at 16.4% (95% CI: 15.3%~17.6%). In studies with the onset age at 20 ~ 29 years old, males had a twice times higher HUA prevalence than females (21.5% vs. 8.9%). The prevalence of HUA was 13.7% (11.8%~15.7%) in people aged 15~ years old, 16.5% in 30~ (14.8%~18.4%), 17.9% in 40~ (16.4%~19.5%), 19.4% in 50~ (17.8%~21.0%), 20.5% in 60~ (18.8%~22.3%), and 24.9% in over 70 (22.9%~27.1%). Stratified by regions, southern (25.5%) and southwestern (21.2%) China shared the highest prevalence, and the lowest prevalence was observed in the northwest (12.6%). From 2001 to 2017, the prevalence estimates of HUA steadily climbed from 8.5% to 18.4% with minor fluctuations. Multiple regression revealed that HUA prevalence was positively correlated to the larger sample size, area, advanced onset age, and published year.
The last two decades witnessed the rapid growth prevalence of HUA in China. Early screening and personalized health education for HUA need to be given enough attention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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