共查询到20条相似文献，搜索用时 15 毫秒
1.
Melissa A. Bellinger James S. Bean Melissa A. Rader Kathleen M. Heinz-Taheny Jairo S. Nunes Joseph V. Haas Laura F. Michael Mark D. Rekhter 《PloS one》2014,9(4)
Background
Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of the kidney excretory function and is strongly associated with increased early and long-term patient morbidity and mortality. Early diagnosis of AKI is challenging; therefore we profiled plasma microRNA in an effort to identify potential diagnostic circulating markers of renal failure. The goal of the present study was to investigate the dynamic relationship of circulating and renal microRNA profiles within the first 24 hours after bilateral ischemia-reperfusion kidney injury in mice.Methodology/Principal Findings
Bilateral renal ischemia was induced in C57Bl/6 mice (n = 10 per group) by clamping the renal pedicle for 27 min. Ischemia-reperfusion caused highly reproducible, progressive, concordant elevation of miR-714, miR-1188, miR-1897-3p, miR-877*, and miR-1224 in plasma and kidneys at 3, 6 and 24 hours after acute kidney injury compared to the sham-operated mice (n = 5). These dynamics correlated with histologic findings of kidney injury and with a conventional plasma marker of renal dysfunction (creatinine). Pathway analysis revealed close association between miR-1897-3p and Nucks1 gene expression, which putative downstream targets include genes linked to renal injury, inflammation and apoptosis.Conclusions/Significance
Systematic profiling of renal and plasma microRNAs in the early stages of experimental AKI provides the first step in advancing circulating microRNAs to the level of promising novel biomarkers. 相似文献2.
Gina M. Howell Hernando Gomez Richard D. Collage Patricia Loughran Xianghong Zhang Daniel A. Escobar Timothy R. Billiar Brian S. Zuckerbraun Matthew R. Rosengart 《PloS one》2013,8(7)
Objective
To determine that 1) an age-dependent loss of inducible autophagy underlies the failure to recover from AKI in older, adult animals during endotoxemia, and 2) pharmacologic induction of autophagy, even after established endotoxemia, is of therapeutic utility in facilitating renal recovery in aged mice.Design
Murine model of endotoxemia and cecal ligation and puncture (CLP) induced acute kidney injury (AKI).Setting
Academic research laboratory.Subjects
C57Bl/6 mice of 8 (young) and 45 (adult) weeks of age.Intervention
Lipopolysaccharide (1.5 mg/kg), Temsirolimus (5 mg/kg), AICAR (100 mg/kg). Measurements and Main Results: Herein we report that diminished autophagy underlies the failure to recover renal function in older adult mice utilizing a murine model of LPS-induced AKI. The administration of the mTOR inhibitor temsirolimus, even after established endotoxemia, induced autophagy and protected against the development of AKI.Conclusions
These novel results demonstrate a role for autophagy in the context of LPS-induced AKI and support further investigation into like interventions that have potential to alter the natural history of disease. 相似文献3.
Fabian Zimmer Frank G. Z?llner Simone Hoeger Sarah Klotz Charalambos Tsagogiorgas Bernhard K. Kr?mer Lothar R. Schad 《PloS one》2013,8(1)
Objectives
To establish arterial spin labelling (ASL) for quantitative renal perfusion measurements in a rat model at 3 Tesla and to test the diagnostic significance of ASL and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a model of acute kidney injury (AKI).Material and Methods
ASL and DCE-MRI were consecutively employed on six Lewis rats, five of which had a unilateral ischaemic AKI. All measurements in this study were performed on a 3 Tesla MR scanner using a FAIR True-FISP approach and a TWIST sequence for ASL and DCE-MRI, respectively. Perfusion maps were calculated for both methods and the cortical perfusion of healthy and diseased kidneys was inter- and intramethodically compared using a region-of-interest based analysis.Results/Significance
Both methods produce significantly different values for the healthy and the diseased kidneys (P<0.01). The mean difference was 147±47 ml/100 g/min and 141±46 ml/100 g/min for ASL and DCE-MRI, respectively. ASL measurements yielded a mean cortical perfusion of 416±124 ml/100 g/min for the healthy and 316±102 ml/100 g/min for the diseased kidneys. The DCE-MRI values were systematically higher and the mean cortical renal blood flow (RBF) was found to be 542±85 ml/100 g/min (healthy) and 407±119 ml/100 g/min (AKI).Conclusion
Both methods are equally able to detect abnormal perfusion in diseased (AKI) kidneys. This shows that ASL is a capable alternative to DCE-MRI regarding the detection of abnormal renal blood flow. Regarding absolute perfusion values, nontrivial differences and variations remain when comparing the two methods. 相似文献4.
Chang Seong Kim Chan Young Oak Ha Yeon Kim Yong Un Kang Joon Seok Choi Eun Hui Bae Seong Kwon Ma Sun-Seog Kweon Soo Wan Kim 《PloS one》2013,8(12)
Background
Postoperative acute kidney injury (AKI), a serious surgical complication, is common after cardiac surgery; however, reports on AKI after noncardiac surgery are limited. We sought to determine the incidence and predictive factors of AKI after gastric surgery for gastric cancer and its effects on the clinical outcomes.Methods
We conducted a retrospective study of 4718 patients with normal renal function who underwent partial or total gastrectomy for gastric cancer between June 2002 and December 2011. Postoperative AKI was defined by serum creatinine change, as per the Kidney Disease Improving Global Outcomes guideline.Results
Of the 4718 patients, 679 (14.4%) developed AKI. Length of hospital stay, intensive care unit admission rates, and in-hospital mortality rate (3.5% versus 0.2%) were significantly higher in patients with AKI than in those without. AKI was also associated with requirement of renal replacement therapy. Multivariate analysis revealed that male gender; hypertension; chronic obstructive pulmonary disease; hypoalbuminemia (<4 g/dl); use of diuretics, vasopressors, and contrast agents; and packed red blood cell transfusion were independent predictors for AKI after gastric surgery. Postoperative AKI and vasopressor use entailed a high risk of 3-month mortality after multiple adjustments.Conclusions
AKI was common after gastric surgery for gastric cancer and associated with adverse outcomes. We identified several factors associated with postoperative AKI; recognition of these predictive factors may help reduce the incidence of AKI after gastric surgery. Furthermore, postoperative AKI in patients with gastric cancer is an important risk factor for short-term mortality. 相似文献5.
Christopher Imokhuede Esezobor Taiwo Augustina Ladapo Babayemi Osinaike Foluso Ebun Afolabi Lesi 《PloS one》2012,7(12)
Background
The modest decline in child mortality in Africa raises the question whether the pattern of diseases associated with acute kidney injury (AKI) in children in Nigeria has changed.Methods
A database of children, aged between one month and 16 years, with AKI (using modified pediatric RIFLE criteria) was reviewed. The cause of AKI was defined as the major underlying disease. The clinical and laboratory features of children with AKI who survived were compared to those who died.Results
Of the 4 015 children admitted into Lagos University Teaching Hospital between July 2010 and July 2012, 70 episodes of AKI were recorded equalling 17.4 cases per 1000 children. The median age of the children with AKI was 4.8 (range 0.1–14.4) years and 68.6% were males. Acute kidney injury was present in 58 (82.9%) children at admission with 70% in ‘failure’ category. Primary kidney disease (38.6%), sepsis (25.7%) and malaria (11.4%) were the commonest causes. The primary kidney diseases were acute glomerulonephritis (11) and nephrotic syndrome (8). Nineteen (28.4%) children with AKI died. Need for dialysis [odds ratio: 10.04 (2.94–34.33)], white cell >15 000/mm3 [odds ratio: 5.72 (1.65–19.89)] and platelet <100 000/mm3 [odds ratio: 9.56 (2.63–34.77)] were associated with death.Conclusion
Acute kidney injury is common in children admitted to hospitals. The common causes remain primary kidney diseases, sepsis and malaria but the contribution of sepsis is rising while malaria and gastroenteritis are declining. Acute kidney injury-related mortality remains high. 相似文献6.
Calpurnia Jayakumar Punithavathi Ranganathan Prasad Devarajan Catherine D. Krawczeski Stephen Looney Ganesan Ramesh 《PloS one》2013,8(3)
Background
Semaphorin 3A is a secreted protein that regulates cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumor progression. However, nothing is known about its role in kidney pathophysiology. Here, we determined whether semaphorin3A is induced after acute kidney injury (AKI) and whether urinary semaphorin 3A can predict AKI in humans undergoing cardiopulmonary bypass (CPB).Methods and Principal Findings
In animals, semaphorin 3A is localized in distal tubules of the kidney and excretion increased within 3 hr after reperfusion of the kidney whereas serum creatinine was significantly raised at 24 hr. In humans, using serum creatinine, AKI was detected on average only 48 hours after CPB. In contrast, urine semaphorin increased at 2 hours after CPB, peaked at 6 hours (2596±591 pg/mg creatinine), and was no longer significantly elevated 12 hours after CPB. The predictive power of semaphorin 3A as demonstrated by area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 12 hours after CPB was 0.88, 0.81, and 0.74, respectively. The 2-hour urine semaphorin measurement strongly correlated with duration and severity of AKI, as well as length of hospital stay. Adjusting for CPB time and gender, the 2-hour semaphorin remained an independent predictor of AKI, with an odds ratio of 2.19.Conclusion
Our results suggest that semaphorin 3A is an early, predictive biomarker in experimental and pediatric AKI, and may allow for the reliable early diagnosis and prognosis of AKI after CPB, much before the rise in serum creatinine. 相似文献7.
Background
The effects of mannitol administration on acute kidney injury (AKI) prevention remain uncertain, as the results from clinical studies were conflicting. Due to the lack of strong evidence, the KDIGO Guideline for AKI did not propose completely evidence-based recommendations on this issue.Methods
We searched PubMed, EMBASE, clinicaltrials.gov and Cochrane Controlled Trials Register. Randomized controlled trials on adult patients at increased risk of AKI were considered on the condition that they compared the effects of intravascular administration of mannitol plus expansion of intravascular volume with expansion of intravascular volume alone. We calculated pooled risk ratios, numbers needed to treat and mean differences with 95% confidence intervals for dichotomous data and continuous data, respectively.Results
Nine trials involving 626 patients were identified. Compared with expansion of intravascular volume alone, mannitol infusion for AKI prevention in high-risk patients can not reduce the serum creatinine level (MD 1.63, 95% CI −6.02 to 9.28). Subgroup analyses demonstrated that serum creatinine level is negatively affected by the use of mannitol in patients undergoing an injection of radiocontrast agents (MD 17.90, 95% CI 8.56 to 27.24). Mannitol administration may reduce the incidence of acute renal failure or the need of dialysis in recipients of renal transplantation (RR 0.34, 95% CI 0.21 to 0.57, NNT 3.03, 95% CI 2.17 to 5.00). But similar effects were not found in patients at high AKI risk, without receiving renal transplantation (RR 0.29, 95% CI 0.01 to 6.60).Conclusions
Intravascular administration of mannitol does not convey additional beneficial effects beyond adequate hydration in the patients at increased risk of AKI. For contrast-induced nephropathy, the use of mannitol is even detrimental. Further research evaluating the efficiency of mannitol infusions in the recipients of renal allograft should be undertaken. 相似文献8.
Xinghua Shao Lei Tian Weijia Xu Zhen Zhang Chunlin Wang Chaojun Qi Zhaohui Ni Shan Mou 《PloS one》2014,9(1)
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. 相似文献9.
Jean-Christophe Orban Eve-Marie Maizière Anis Ghaddab Emmanuel Van Obberghen Carole Ichai 《PloS one》2014,9(10)
Aims
Acute kidney injury is a classical complication of diabetic ketoacidosis. However, to the best of our knowledge, no study has reported the incidence and characteristics of acute kidney injury since the consensus definition was issued.Methods
Retrospective study of all cases of severe diabetic ketoacidosis hospitalised consecutively in a medical surgical tertiary ICU during 10 years. Patients were dichotomised in with AKI and without AKI on admission according to the RIFLE classification. Clinical and biological parameters were compared in these populations. Risk factors of presenting AKI on admission were searched for.Results
Ninety-four patients were included in the study. According to the RIFLE criteria, 47 patients (50%) presented acute kidney injury on admission; most of them were in the risk class (51%). At 12 and 24 hours, the percentage of AKI patients decreased to 26% and 27% respectively. During the first 24 hours, 3 patients needed renal replacement therapy. Acute renal failure on admission was associated with a more advanced age, SAPS 2 and more severe biological impairments. Treatments were not different between groups except for insulin infusion. Logistic regression found 3 risk factors of presenting AKI on admission: age (odds ratio 1.060 [1.020–1.100], p<0.01), blood glucose (odds ratio 1.101 [1.039–1.166], p<0.01) and serum protein (odds ratio 0.928 [0.865–0.997], p = 0.04).Conclusions
Acute kidney injury is frequently associated with severe diabetic ketoacidosis on admission in ICU. Most of the time, this AKI is transient and characterised by a volume-responsiveness to fluid infusion used in DKA treatment. Age, blood glucose and serum protein are associated to the occurrence of AKI on ICU admission. 相似文献10.
Michael E. Matheny Josh F. Peterson Svetlana K. Eden Adriana M. Hung Theodore Speroff Khaled Abdel-Kader Sharidan K. Parr T. Alp Ikizler Edward D. Siew 《PloS one》2014,9(8)
Background
Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort.Methods
We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients.Results
A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients.Conclusions
Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease. 相似文献11.
Emmanuel Canet Lara Zafrani Jerome Lambert Catherine Thieblemont Lionel Galicier David Schnell Emmanuel Raffoux Etienne Lengline Sylvie Chevret Michael Darmon Elie Azoulay 《PloS one》2013,8(2)
Background
Optimal chemotherapy with minimal toxicity is the main determinant of complete remission in patients with newly diagnosed hematological malignancies. Acute organ dysfunctions may impair the patient’s ability to receive optimal chemotherapy.Design and Methods
To compare 6-month complete remission rates in patients with and without acute kidney injury (AKI), we collected prospective data on 200 patients with newly diagnosed high-grade malignancies (non-Hodgkin lymphoma, 53.5%; acute myeloid leukemia, 29%; acute lymphoblastic leukemia, 11.5%; and Hodgkin disease, 6%).Results
According to RIFLE criteria, 137 (68.5%) patients had AKI. Five causes of AKI accounted for 91.4% of cases: hypoperfusion, tumor lysis syndrome, tubular necrosis, nephrotoxic agents, and hemophagocytic lymphohistiocytosis. Half of the AKI patients received renal replacement therapy and 14.6% received suboptimal chemotherapy. AKI was associated with a lower 6-month complete remission rate (39.4% vs. 68.3%, P<0.01) and a higher mortality rate (47.4% vs. 30.2%, P<0.01) than patients without AKI. By multivariate analysis, independent determinants of 6-month complete remission were older age, poor performance status, number of organ dysfunctions, and AKI.Conclusion
AKI is common in patients with newly diagnosed high-grade malignancies and is associated with lower complete remission rates and higher mortality. 相似文献12.
13.
Melanie Meersch Christoph Schmidt Hugo Van Aken Jan Rossaint Dennis G?rlich Dirk Stege Edward Malec Katarzyna Januszewska Alexander Zarbock 《PloS one》2014,9(10)
Background
The lack of early biomarkers for acute kidney injury (AKI) seriously inhibits the initiation of preventive and therapeutic measures for this syndrome in a timely manner. We tested the hypothesis that insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, function as early biomarkers for AKI after congenital heart surgery with cardiopulmonary bypass (CPB).Methods
We prospectively studied 51 children undergoing cardiac surgery with CPB. Serial urine samples were analyzed for [TIMP-2]•[IGFBP7]. The primary outcome measure was AKI defined by the pRIFLE criteria within 72 hours after surgery.Results
12 children (24%) developed AKI within 1.67 (SE 0.3) days after surgery. Children who developed AKI after cardiac surgery had a significant higher urinary [TIMP-2]•[IGFBP7] as early as 4 h after the procedure, compared to children who did not develop AKI (mean of 1.93 ((ng/ml)2/1000) (SE 0.4) vs 0.47 ((ng/ml)2/1000) (SE 0.1), respectively; p<0.05). Urinary [TIMP-2]•[IGFBP7] 4 hours following surgery demonstrated an area under the receiver-operating characteristic curve of 0.85. Sensitivity was 0.83, and specificity was 0.77 for a cutoff value of 0.70 ((ng/ml)2/1000).Conclusions
Urinary [TIMP-2]•[IGFBP7] represent sensitive, specific, and highly predictive early biomarkers for AKI after surgery for congenital heart disease.Trial Registration
www.germanctr.de/, DRKS00005062 相似文献14.
Background
Detachment of photoreceptors from the underlying retinal pigment epithelium is seen in various retinal disorders such as retinal detachment and age-related macular degeneration and leads to loss of photoreceptors and vision. Pharmacologic inhibition of photoreceptor cell death may prevent this outcome. This study tests whether systemic administration of tauroursodeoxycholic acid (TUDCA) can protect photoreceptors from cell death after experimental retinal detachment in rodents.Methodology/Principal Findings
Retinal detachment was created in rats by subretinal injection of hyaluronic acid. The animals were treated daily with vehicle or TUDCA (500 mg/kg). TUNEL staining was used to evaluate cell death. Photoreceptor loss was evaluated by measuring the relative thickness of the outer nuclear layer (ONL). Macrophage recruitment, oxidative stress, cytokine levels, and caspase levels were also quantified. Three days after detachment, TUDCA decreased the number of TUNEL-positive cells compared to vehicle (651±68/mm2 vs. 1314±68/mm2, P = 0.001) and prevented the reduction of ONL thickness ratio (0.84±0.03 vs. 0.65±0.03, P = 0.002). Similar results were obtained after 5 days of retinal detachment. Macrophage recruitment and expression levels of TNF-a and MCP-1 after retinal detachment were not affected by TUDCA treatment, whereas increases in activity of caspases 3 and 9 as well as carbonyl-protein adducts were almost completely inhibited by TUDCA treatment.Conclusions/Significance
Systemic administration of TUDCA preserved photoreceptors after retinal detachment, and was associated with decreased oxidative stress and caspase activity. TUDCA may be used as a novel therapeutic agent for preventing vision loss in diseases that are characterized by photoreceptor detachment. 相似文献15.
Nicholas M. Selby Nitin V. Kolhe Christopher W. McIntyre John Monaghan Nigel Lawson David Elliott Rebecca Packington Richard J. Fluck 《PloS one》2012,7(11)
Background
The high mortality rates that follow the onset of acute kidney injury (AKI) are well recognised. However, the mode of death in patients with AKI remains relatively under-studied, particularly in general hospitalised populations who represent the majority of those affected. We sought to describe the primary cause of death in a large group of prospectively identified patients with AKI.Methods
All patients sustaining AKI at our centre between 1st October 2010 and 31st October 2011 were identified by real-time, hospital-wide, electronic AKI reporting based on the Acute Kidney Injury Network (AKIN) diagnostic criteria. Using this system we are able to generate a prospective database of all AKI cases that includes demographic, outcome and hospital coding data. For those patients that died during hospital admission, cause of death was derived from the Medical Certificate of Cause of Death.Results
During the study period there were 3,930 patients who sustained AKI; 62.0% had AKI stage 1, 20.6% had stage 2 and 17.4% stage 3. In-hospital mortality rate was 21.9% (859 patients). Cause of death could be identified in 93.4% of cases. There were three main disease categories accounting for three quarters of all mortality; sepsis (41.1%), cardiovascular disease (19.2%) and malignancy (12.9%). The major diagnosis leading to sepsis was pneumonia, whilst cardiovascular death was largely a result of heart failure and ischaemic heart disease. AKI was the primary cause of death in only 3% of cases.Conclusions
Mortality associated with AKI remains high, although cause of death is usually concurrent illness. Specific strategies to improve outcomes may therefore need to target not just the management of AKI but also the most relevant co-existing conditions. 相似文献16.
Karoly Kalmar-Nagy Peter Degrell Aliz Szabo Katalin Sumegi Istvan Wittmann Ferenc Gallyas Jr Balazs Sumegi 《PloS one》2013,8(12)
Background
Novel immunosuppressive therapy facilitates long term allograft survival, but acute tubular necrosis and ischemia-reperfusion during transplantation can compromise allograft function. These processes are related to oxidative stress which activates poly- (ADP-ribose) polymerase (PARP) contributing to the activation of cell death pathways. Here we raised the possibility that PARP inhibition curbs cell death pathways and shifts kinase signaling to improved graft survival.Methods Findings
In an acute rat kidney rejection model, we provided evidence that the PARP inhibitor 4-hydroxy-quinazoline (4OHQ) attenuates rejection processes initiated oxidative/nitrosative stress, nuclear poly-ADP-ribosylation and the disintegration of the tubulo-interstitial structures. The PARP inhibitor attenuated rejection processes induced pro-apoptotic pathways by increasing Bcl-2/Bax ratio and suppressing pro-apoptotic t-Bid levels. In transplanted kidneys, the cell death inducing JNK1/2 is normally activated, but PARP inhibition suppressed this activation with having only modest effects on ERK1/2 and p38 MAP kinases. In untreated transplanted kidneys, no significant alterations were detected in the cytoprotective PI-3K-Akt pathway, but the PARP inhibitor significantly activated Akt (by S473 phosphorylation) and suppressed GSK-3β, as well as activated acute NF-kappaB activation contributing to graft protection.Conclusion
These data show the protective role of PARP inhibition on graft survival by attenuating poly-ADP-ribosylation, oxidative stress, suppressing pro-apoptotic and increasing anti-apoptotic protein level, and by shifting MAP kinases and PI-3-K-Akt pathways to cytoprotective direction. Thus, addition of PARP inhibitors to standard immunosuppressive therapies during kidney transplantation may provide increased protection to prolong graft survival. 相似文献17.
Vin-Cent Wu Chen-Yi Wang Chih-Chung Shiao Chia-Hsui Chang Hui-Yu Huang Tao-Min Huang Chun-Fu Lai Meng-Chun Lin Wen-Je Ko Kwan-Dun Wu Chong-Jen Yu Chin-Chung Shu Chih-Hsin Lee Jann-Yuan Wang the National Taiwan University Study Group on Acute Renal Failure Taiwan Anti-Mycobacteria Investigation Group 《PloS one》2013,8(7)
Background
Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited.Methods
This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999–2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization.Results
Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032).Conclusions
AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB. 相似文献18.
Background
A sudden mechanical insult to the spinal cord is usually caused by changing pressure on the surface of the spinal cord. Most of these insults are mechanical force injuries, and their mechanism of injury to the spinal cord is largely unknown.Methods
Using a compression-driven instrument to simulate mechanical force, we applied mechanical pressure of 0.5 MPa to rat dorsal root ganglion (DRG) neurons for 10 min to investigate cytoskeletal alterations and calpain-induced apoptosis after the mechanical force injury.Results
The results indicated that mechanical forces affect the structure of the cytoskeleton and cell viability, induce early apoptosis, and affect the cell cycle of DRG neurons. In addition, the calpain inhibitor PD150606 reduced cytoskeletal degradation and the rate of apoptosis after mechanical force injury.Conclusion
Thus, calpain may play an important role in DRG neurons in the regulation of apoptosis and cytoskeletal alterations induced by mechanical force. Moreover, cytoskeletal alterations may be substantially involved in the mechanotransduction process in DRG neurons after mechanical injury and may be induced by activated calpain. To our knowledge, this is the first report to demonstrate a relationship between cytoskeletal degradation and apoptosis in DRG neurons. 相似文献19.
Chih-Hsiang Chang Pei-Chun Fan Ming-Yang Chang Ya-Chung Tian Cheng-Chieh Hung Ji-Tseng Fang Chih-Wei Yang Yung-Chang Chen 《PloS one》2014,9(10)
Introduction
Acute kidney injury (AKI) is a common and serious complication in intensive care unit (ICU) patients and also often part of a multiple organ failure syndrome. The sequential organ failure assessment (SOFA) score is an excellent tool for assessing the extent of organ dysfunction in critically ill patients. This study aimed to evaluate the outcome prediction ability of SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) III score in ICU patients with AKI.Methods
A total of 543 critically ill patients were admitted to the medical ICU of a tertiary-care hospital from July 2007 to June 2008. Demographic, clinical and laboratory variables were prospectively recorded for post hoc analysis as predictors of survival on the first day of ICU admission.Results
One hundred and eighty-seven (34.4%) patients presented with AKI on the first day of ICU admission based on the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification. Major causes of the ICU admissions involved respiratory failure (58%). Overall in-ICU mortality was 37.9% and the hospital mortality was 44.7%. The predictive accuracy for ICU mortality of SOFA (areas under the receiver operating characteristic curves: 0.815±0.032) was as good as APACHE III in the AKI group. However, cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.001) for SOFA score ≤10 vs. ≥11 in these ICU patients with AKI.Conclusions
For patients coexisting with AKI admitted to ICU, this work recommends application of SOFA by physicians to assess ICU mortality because of its practicality and low cost. A SOFA score of ≥ “11” on ICU day 1 should be considered an indicator of negative short-term outcome. 相似文献20.
Rhea Bhargava Christopher J. Altmann Ana Andres-Hernando Ryan G. Webb Kayo Okamura Yimu Yang Sandor Falk Eric P. Schmidt Sarah Faubel 《PloS one》2013,8(11)