Epigenetic regulation in the acute kidney injury to chronic kidney disease transition

Epigenetic modifications have emerged as a new, important contributor to gene expression regulation in both normal and pathophysiological conditions. Epigenetics have been studied in many diseases and conditions such as acute kidney injury (AKI), a syndrome with a high prevalence that carries a poor prognosis with increased morbidity and mortality. In addition, it has recently been shown that AKI increases the risk for the development of chronic kidney disease (CKD). The specific molecular mechanisms by which AKI increases the risk of CKD and end stage renal disease (ESRD) remain unknown, although there is new evidence supporting a role of epigenetic changes. The most studied epigenetic regulations in AKI are chromatin compaction, DNA methylation, and histone acetylation/deacetylation. These modifications predominantly increase the production of pro‐inflammatory and profibrotic cytokines such as: monocyte chemoattractant protein‐1 (MCP‐1), complement protein 3 (C3), transforming growth factor β (TGF‐β) that have been shown for perpetuating inflammation, promoting epithelial‐to‐mesenchymal transition (EMT) and ultimately causing renal fibrosis. A review of epigenetic mechanisms, the pathophysiology of AKI and recent studies that implicate epigenetic modifications in AKI and in the transition to CKD are discussed below.     

肘关节慢性运动损伤的MRI研究

目的:探讨应用磁共振(MR)成像检查肘关节慢性运动损伤的经验和图像特点。方法:采取MR矢状位、冠状位及轴位扫描,分析2005年9月至2008年5月34名运动员共40侧慢性肘关节损伤的MR特点,男21例,女13例;年龄6～16岁,平均(12.3±3.1)岁。结果:慢性肘关节损伤的MR表现为尺骨鹰嘴滑囊增厚、积液,肱骨下段骨骺、桡骨小头、尺骨鹰嘴、尺骨冠突骨髓水肿,尺侧副韧带损伤。结论:MR检查肘关节可明确显示关节内外的骨骼肌肉组织的损伤情况,是一种敏感有效无创伤的方法。     

Magnetic resonance imaging (MRI): Method and early clinical experiences in diseases of the central nervous system

Summary Magnetic resonance imaging (MRI) has undergone a rapid development which is still continuing. In this article a survey is given of the present status of this new diagnostic tool in the evaluation of diseases of the central nervous system.When atoms with uneven numbers of protons or neutrons in a homogeneous magnetic field are tilted against the main vector of this field by a radiofrequency pulse, nuclear magnetic resonance can be observed. During the relaxation of the little dipoles back to the direction of the underlying magnetic field, a resonance signal is generated. The superposition of variable field gradients enables the scanning of sectional images in the axial, frontal and sagittal plane.The variables of H⁺-magnetic resonance which can be utilized for imaging are: the proton density, the relaxation times T₁ (spin-lattice) and T₂ (spin-spin) and flow effects. While the proton density in organic tissue fluctuates only by some 10%, the relaxation times may vary by several hundred per cent. Tissue contrast, therefore, is mainly based on relaxation times differences. The image character can also be influenced by variations of imaging parameters (i.e. repetition rate, interpulse delay, read out or echo delay) in different imaging sequences, such as the spin-echo and the inversion recovery technique. Depending on these imaging parameters T₁ and T₂ will contribute to the signal to a varying degree. This fact is most important for the diagnostic information of MRI.In initial clinical experiences in the diagnosis of diseases of the central nervous system, MRI has demonstrated high sensitivity in the detection of lesions (such as oedema, neoplasms, demyelinating disease), but less significance in lesion discrimination.In spinal disease the direct sagittal imaging of MRI enables MRI-myelography without contrast medium, superior to conventional myelography in many cases. For detailed evaluation of disc disease, however, the spatial resolution still has to be improved.Promising results have been obtained from flow effects. Depending on the flow velocity of blood, vessels appear white with intensive signals (slow flow) or black due to low signal intensities (rapid flow). MRI-angiography including measurement of blood flow seems possible.MRI-contrast media are not yet available for routine clinical use. Promising results have been reported on the basis of rare-earth elements, such as gadolinium Gd³⁺. These substances decrease T₁ and T₂ with subsequent increase in signal intensity.Concerning harmful side-effects of MRI, three possible sources have to be considered: the static magnetic field, the changing magnetic field, and radiofrequency heating. No permanent damage to organisms has been described up to the present time, in relation to the magnetic field strength used in MRI. However, there is known risk for patients who carry cardiac pace makers or metal implants such as aneurysm clips.     

Decline in kidney function before and after nephrology referral and the effect on survival in moderate to advanced chronic kidney disease.

BACKGROUND: The burden of chronic kidney disease (CKD) is high, but its natural history and the benefit of routine nephrology care is unclear. This study investigated the decline in kidney function prior to and following nephrology referral and its association with mortality. METHODS: This study provides a retrospective review of the individual rates of glomerular filtration rate (GFR) decline (millilitre per minute per 1.73 m(2)/year) for the 5 years before and after referral in 726 new referrals with stages 3-5 CKD to one renal unit between 1997 and 2003. Blood pressures are averages at referral, 1 and 3 years post referral. Logistic regression and Cox's models tested factors predicting post-referral GFR decline and the impact on mortality. RESULTS: Mean (SD) age was 72 (14), and 389 (54%) patients had stages 4-5 CKD. GFR decline slowed significantly from -5.4 ml/min/1.73 m(2)/year (-13. to -2) before to -0.35 ml/min/1.73 m(2)/year (-3 to +3) after referral (P < 0.001). Blood pressure also reduced significantly (155/84 to 149/80, P < 0.05) with most changes occurring within 1 year of referral. Factors predicting a non-progressive post-referral decline included a lower systolic blood pressure at referral and 1 year after referral, a CKD diagnosis other than diabetic nephropathy, less baseline proteinuria and a non-progressive pre-referral GFR decline. A non-progressive post-referral GFR decline was independently associated with significantly better survival (hazard ratio 0.55, 95% CI 0.40-0.75, P 相似文献   

Magnetic resonance imaging and neurological recovery in acute spinal cord injury: observations from the National Acute Spinal Cord Injury Study 3

STUDY DESIGN: Data are from a multicenter, randomized, double blind clinical trial of acute spinal cord injury. OBJECTIVES: To evaluate the prognostic value of magnetic resonance imaging (MRI) for randomized patients in the National Acute Spinal Cord Injury Study 3 (NASCIS). SETTING: Sixteen spinal cord injury centers throughout the United States and Canada. METHODS: Of 499 patients randomized in NASCIS 3 between December 1991 and September 1995, MRI was electively done on 191 patients within 72 h of injury. Indications of hemorrhage, edema, and contusion were recorded by standard protocol. Neurological impairment as determined by motor function, response to pin prick and light touch was assessed at admission to the participating center and 6 weeks after injury. Change in neurological function was obtained by subtracting the score of each neurological parameter at admission from that measured at 6 weeks. Spinal cord surgery performed within the 3 days after injury was noted. Data were analyzed by: chi square, analysis of variance, multiple logistic regression and linear regression models. RESULTS: Patients with hemorrhage were much more likely to have a complete injury (OR=2.88, 95 Cl 1.32, 6.23); however this association was much reduced when the initial neurological examination was taken into account (AOR=1.43, 95% Cl 0.55, 3.73) and was no longer a significant predictor of injury. MRI evidence of cord edema was the strongest predictor of reduced improvement in motor function (-3.34 points, P=0.06) and light touch sensation (-3.41 points, P=0.05) at 6 weeks. CONCLUSIONS: Cord hemorrhage, contusion, and edema on MRI were not associated with diagnosis of a complete cord injury after neurological assessment from the initial clinical examination was taken into account. Prediction of a worse 6 week neurological status was weakly associated with the presence of edema diagnosed by MRI. As MRI technology improves, these diagnostic and predictive capabilities need to be re-assessed. SPONSORSHIP: NASCIS 3 was funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, Washington, DC, USA. Pharmacia and Upjohn provided study drugs and placebos; they also monitored data quality, and funded additional tests, in accordance with Food and Drug Administration regulatory requirements. Dr Bracken has served as an occasional paid consultant to Pharmacia and Upjohn.     

Magnetic resonance imaging and morphometric histologic analysis of prostate tissue composition in predicting the clinical outcome of terazosin therapy in benign prostatic hyperplasia

PURPOSE: To determine whether magnetic resonance imaging (MRI) or quantitative color-imaged morphometric analysis (MA) of the prostate gland are related to the clinical response to terazosin. METHODS: Thirty-six male patients with symptomatic benign prostatic hyperplasia (BPH) with a serum prostate-specific antigen level of 4-10 ng/mL underwent MRI with body coil, transrectal prostate ultrasonography and biopsy prior to terazosin therapy. For MRI-determined stromal and non-stromal BPH, the ratio of the signal intensity of the inner gland to the obturator internus muscle was evaluated. Histologic sections were stained with hematoxylin and eosin. The MA of the specimens was performed by Samba 2000. Results of the two techniques were interpreted according to the terazosin therapy results. RESULTS: The mean stromal percentage was 60.5 +/- 18.0%. No statistically significant relationship was found between the clinical outcome of terazosin and the MRI findings. The MA results showed a significant relationship between the percentage of stroma and the percent change of the peak urinary flow rate, but not with the percent change of the international prostate symptom score after terazosin therapy (P < 0.05). CONCLUSION: Magnetic resonance imaging alone is not sufficient in predicting the response to terazosin therapy. Morphometric analysis of BPH tissue composition can be used in predicting the clinical outcome of terazosin therapy but it is suitable only in patients for whom prostatic biopsy is necessary in order to rule out prostate cancer.     

Comparison between early and delayed acute kidney injury secondary to infectious disease in the intensive care unit

BACKGROUND: Results from a number of studies suggest that the delayed manifestation of acute kidney injury (AKI) is associated with higher in-hospital mortality, while other studies were unable to demonstrate any difference among early and delayed AKI in terms of in-hospital mortality. OBJECTIVE: The aim of this study was to investigate differences in outcome among patients with AKI upon admission to an intensive care unit (ICU) and those who develop AKI post-admission. METHODS: We studied patients with AKI secondary to infectious diseases admitted to the ICU. We retrospectively compared data on patients admitted with AKI (early AKI) with data on those who developed AKI 24 h after admission (delayed AKI). RESULTS: Acute kidney injury occurred in 147 of 829 (17.7%) patients admitted to the ICU. Of these, 96 (65%) had early AKI and 51 (35%) had delayed AKI. Renal failure was classified according to RIFLE criteria-an AKI-specific severity score that is used to place patients into one of five categories: risk, injury, failure, loss or end-stage renal disease. Based on these criteria, 6% of the early AKI and 4% of the delayed AKI patients were in risk category, 18% of the early AKI and 27% of the delayed AKI patients were in the injury category and 76% of the early AKI and 69% of the delayed AKI patients were in the failure category. We found no significant association between RIFLE and death. On admission, patients with early AKI had statistically significantly higher serum urea and creatinine levels than delayed AKI patients (P < 0.0001). Arterial bicarbonate was lower in early AKI (P = 0.02). Sepsis, hypotension and use of mechanical ventilation were more frequent in delayed AKI (P < 0.05). The APACHE II score was higher in early AKI (P = 0.05) patients. In total, 98 (66.7%) patients died, with a tendency towards higher mortality in patients with delayed AKI (61.5 vs. 76.5%, P = 0.07). CONCLUSION: Mortality among patients with infectious diseases-associated AKI admitted to the ICU is high, with a trend to be higher in those who developed delayed AKI.     

Anticoagulation therapy and the risk of perioperative brain injury in neonates with congenital heart disease

ObjectiveThere is considerable variability in anticoagulation use in neonates with transposition of the great arteries (TGA) and single ventricle physiology (SVP) for secondary stroke prevention and primary cardiovascular indications. Leveraging cross-center differences in anticoagulation use, we compared the risk of new postoperative brain injury in neonates with TGA and SVP treated with anticoagulation relative to untreated neonates.MethodsTwo-center observational cohort study of 118 term-born neonates with TGA (n = 83) and SVP (n = 35), undergoing cardiopulmonary bypass surgery and pre- and postoperative brain magnetic resonance imaging. Anticoagulation and antiplatelet therapy details were obtained. Magnetic resonance images were scored for stroke, white matter injury, and hemorrhage. New postoperative injury was compared between neonates with and without anticoagulation for the 2-center cohort, and subsequently stratified by cardiac lesion type and anticoagulation indication.ResultsThirty-six out of 118 neonates (29%) received anticoagulation: 11 (30%) for preoperative stroke, 20 (56%) for preoperative peripheral/intracardiac thrombus, and 5 (14%) for Blalock-Taussig shunt. Five out of 36 neonates (14%) treated with anticoagulation also received antiplatelet therapy. Although no differences were identified for the 2-center cohort or for neonates with TGA separately, significantly more new postoperative parenchymal brain injury (P = .04), particularly stroke, was found in SVP neonates with compared to without anticoagulation (31% vs 5%). In neonates who experienced preoperative stroke, new subdural hemorrhage (36% vs 0%) was more frequent in neonates treated with anticoagulation therapy compared with those without anticoagulation therapy.ConclusionsIn our cohort of neonates with TGA and SVP, anticoagulation for preoperative stroke, preoperative thrombus, and/or Blalock-Taussig shunt did not have the anticipated benefit of preventing new perioperative brain injury. These findings indicate the critical need for rigorous randomized trials on the safety and effectiveness of anticoagulation therapy in this population.