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Find video protocols related to scientific articles indexed in Pubmed.
Prevalence and correlates of gout in a large cohort of patients with chronic kidney disease: the German Chronic Kidney Disease (GCKD) study.
Nephrol. Dial. Transplant.
PUBLISHED: 11-15-2014
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Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study.
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Circulating Long Noncoding RNA TapSAKI Is a Predictor of Mortality in Critically Ill Patients with Acute Kidney Injury.
Clin. Chem.
PUBLISHED: 10-07-2014
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Long noncoding RNAs (lncRNAs) are novel intracellular noncoding ribonucleotides regulating gene expression. Intriguingly, these RNA transcripts are detectable and stable in the blood of patients with cancer and cardiovascular disease. We tested whether circulating lncRNAs in plasma of critically ill patients with acute kidney injury (AKI) at inception of renal replacement therapy were deregulated and might predict survival.
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Total collected dialysate lithium concentration after successful dialysis treatment in case of intoxication.
BMC Pharmacol Toxicol
PUBLISHED: 09-06-2014
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Lithium intoxication has potentially fatal neurologic and cardiac side effects. Extracorporeal removal can therefore be lifesaving. The dialysance of lithium is high as it is a small molecule. Comparable to its neighbor in the periodic table, sodium, its intracellular accumulation hampers its removal by renal replacement therapy, despite its favorable size. For this reason the combination of short intermittent and prolonged dialysis may be a beneficial approach in acute lithium intoxication, yet only a report of such a combination has been published and actual removed lithium has not been quantified.
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Guidelines for reporting case studies on extracorporeal treatments in poisonings: methodology.
Semin Dial
PUBLISHED: 05-29-2014
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A literature review performed by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup highlighted deficiencies in the existing literature, especially the reporting of case studies. Although general reporting guidelines exist for case studies, there are none in the specific field of extracorporeal treatments in toxicology. Our goal was to construct and propose a checklist that systematically outlines the minimum essential items to be reported in a case study of poisoned patients undergoing extracorporeal treatments. Through a modified two-round Delphi technique, panelists (mostly chosen from the EXTRIP workgroup) were asked to vote on the pertinence of a set of items to identify those considered minimally essential for reporting complete and accurate case reports. Furthermore, independent raters validated the clarity of each selected items between each round of voting. All case reports containing data on extracorporeal treatments in poisoning published in Medline in 2011 were reviewed during the external validation rounds. Twenty-one panelists (20 from the EXTRIP workgroup and an invited expert on pharmacology reporting guidelines) participated in the modified Delphi technique. This group included journal editors and experts in nephrology, clinical toxicology, critical care medicine, emergency medicine, and clinical pharmacology. Three independent raters participated in the validation rounds. Panelists voted on a total of 144 items in the first round and 137 items in the second round, with response rates of 96.3% and 98.3%, respectively. Twenty case reports were evaluated at each validation round and the independent raters' response rate was 99.6% and 98.8% per validation round. The final checklist consists of 114 items considered essential for case study reporting. This methodology of alternate voting and external validation rounds was useful in developing the first reporting guideline for case studies in the field of extracorporeal treatments in poisoning. We believe that this guideline will improve the completeness and transparency of published case reports and that the systematic aggregation of information from case reports may provide early signals of effectiveness and/or harm, thereby improving healthcare decision-making.
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Therapeutic plasma exchange as rescue therapy in severe sepsis and septic shock: retrospective observational single-centre study of 23 patients.
BMC Anesthesiol
PUBLISHED: 03-31-2014
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Several case series and small randomized controlled trials suggest that therapeutic plasma exchange (TPE) improves coagulation, hemodynamics and possibly survival in severe sepsis. However, the exact role of TPE in modern sepsis therapy remains unclear.
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Circulating Angiopoietin-2 levels predict mortality in kidney transplant recipients: a 4-year prospective case-cohort study.
Transpl. Int.
PUBLISHED: 02-24-2014
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Angiopoietin 2 (Angpt2) impairs endothelial function by preventing angiopoietin 1 from binding to their common endothelial-specific receptor Tie2. Here, we examined whether circulating Angpt2 predicts outcome in kidney transplant recipients. For this case-cohort study, we selected 130 kidney transplant recipients who had died or returned to dialysis within the first 2 years of follow-up of our cohort study, as well as 130 age- and gender-matched kidney transplant recipients without an event (controls) from a total of 993 kidney transplant recipients. The total of 260 selected patients were followed in median 4 years. Serum Angpt2 at baseline was measured using an in-house immunoluminometric assay. Median Angpt2 concentrations were significantly higher in patients who died [median (interquartile range--IQR) 3.6 (2.8-5.9) ng/ml] as compared to patients who did not die during the study period [2.8 (2.1-4.1) ng/ml; P < 0.001]. Ln (natural log) Angpt2 levels correlated positively with C-reactive protein levels (r = 0.315, P < 0.001) and the Charlson Comorbidity Index (r = 0.188, P = 0.002) and were inversely associated with eGFR (r = -0.301, P < 0.001) hemoglobin (r = -0.269, P < 0.001), and serum albumin concentrations (r = -0.382, P < 0.001). On multivariate analyses, baseline Angpt2 levels independently predicted all-cause mortality (multivariable-adjusted hazard ratio associated with one natural log unit higher Angpt2 level: 1.70 (95% confidence interval: 1.10-2.61)). In our analysis, circulating Angpt2 was an independent predictor of all-cause mortality in stable, prevalent kidney transplant recipients.
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Dimethylarginines ADMA and SDMA: the real water-soluble small toxins?
Semin. Nephrol.
PUBLISHED: 02-17-2014
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Uremia occurs if the kidney loses the ability to eliminate toxic compounds at a sufficient rate into the urine. In 1970, N-N, N-G- and N-G,N?-G-dimethyl-arginine (asymmetric dimethylarginine [ADMA] and symmetric dimethylarginine) were isolated from human urine. It was anticipated that both substances might be important in the pathophysiology and for the diagnosis of various pathologic states. It took 22 years, however, before this idea materialized when it was found that ADMA, which is increased in hemodialysis patients, inhibits the synthesis of the endothelial-derived relaxing factor, identified as nitric oxide. ADMA correlates with traditional and nontraditional cardiovascular risk factors and is a strong predictor of cardiovascular events and death in both patients with chronic kidney disease and in the general population. It also seems to mediate adverse cardiovascular effects of drugs such as proton pump inhibitors. To date, we have no specific pharmacologic therapy at hand to neutralize the deleterious effects of ADMA, curbing the enthusiasm for this marker and mediator of cardiovascular disease.
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A missed opportunity - consequences of unknown levetiracepam pharmacokinetics in a peritoneal dialysis patient.
BMC Nephrol
PUBLISHED: 01-20-2014
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Levetiracetam is a frequently used drug in the therapy of partial onset, myoclonic and generalized tonic-clonic seizures. The main route of elimination is via the kidneys, which eliminate 66% of the unchanged drug as well as 24% as inactive metabolite that stems from enzymatic hydrolysis. Therefore dose adjustments are needed in patients with chronic kidney disease stage 5 D, i.e. patients undergoing dialysis treatment. In this patient population a dose reduction by 50% is recommended, so that patients receive 250-750 mg every 12 hours. However "dialysis" can be performed in using different modalities and treatment intensities. For most of the drugs pharmacokinetic data and dosing recommendations for patients undergoing peritoneal dialysis are not available. This is the first report on levetiracetam pharmacokinetics in a peritoneal dialysis patient.
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Removal characteristics and total dialysate content of glutamine and other amino acids in critically ill patients with acute kidney injury undergoing extended dialysis.
Nephron Clin Pract
PUBLISHED: 01-06-2014
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Acute kidney injury in critically ill patients is associated with the activation of protein catabolism and a negative nitrogen balance. Renal replacement therapy (RRT) aggravates this problem by eliminating a substantial amount of amino acids. However, there is scarce data on the removal characteristics of modern dialysis membranes in extended dialysis.
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Psychiatric symptoms in patients with Shiga toxin-producing E. coli O104:H4 induced haemolytic-uraemic syndrome.
PLoS ONE
PUBLISHED: 01-01-2014
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In May 2011 an outbreak of Shiga toxin-producing enterohaemorrhagic E. coli (STEC) O104:H4 in Northern Germany led to a high number of in-patients, suffering from post-enteritis haemolytic-uraemic syndrome (HUS) and often severe affection of the central nervous system. To our knowledge so far only neurological manifestations have been described systematically in literature.
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Association of angiopoietin-2 and dimethylarginines with complicated course in patients with leptospirosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Leptospirosis is one of the most relevant zoonosis worldwide and a potentially life-threatening infectious disease. While it is frequent in tropic regions, it is uncommon in European industrialized countries. Angiopoietin-2 (Angpt-2) and asymmetric and symmetric dimethylarginine (ADMA and SDMA) are markers of endothelial activation and systemic inflammation. These parameters have been studied recently in the context of sepsis and MODS showing potential to determine disease severity and outcome specific parameters like acute kidney injury (AKI) and survival. These biomarkers were measured in 13 patients with leptospirosis. High levels of Angpt-2 were statistically significant associated with a complicated clinical course with occurrence of AKI, Sepsis and intensive care unit treatment. ADMA was significantly associated with occurrence of AKI and ICU treatment whereas SDMA was associated with AKI. Therefore these endothelial markers may serve as additional tools for risk stratification in these patients.
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Imaging in anatomy: a comparison of imaging techniques in embalmed human cadavers.
BMC Med Educ
PUBLISHED: 08-12-2013
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A large variety of imaging techniques is an integral part of modern medicine. Introducing radiological imaging techniques into the dissection course serves as a basis for improved learning of anatomy and multidisciplinary learning in pre-clinical medical education.
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Increased atherosclerotic lesion formation and vascular leukocyte accumulation in renal impairment are mediated by interleukin-17A.
Circ. Res.
PUBLISHED: 08-01-2013
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Atherosclerosis is a major cause of death in patients with chronic kidney disease. Chronic inflammation of the arterial wall including invasion, proliferation, and differentiation of leukocytes is important in atherosclerotic lesion development. How atherosclerotic inflammation is altered in renal impairment is incompletely understood.
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Successful treatment of life threatening theophylline intoxication in a pregnant patient by hemodialysis.
Clin. Nephrol.
PUBLISHED: 06-26-2013
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High-flux hemodialysis is the extracorporeal treatment of choice for various life threatening intoxications. Most published reports support the use of hemoperfusion in the context of severe theophylline poisoning, but the technique is limited by its significant side-effects. We present a potentially life threatening theophylline overdose treated with hemodialysis in a pregnant patient. For the first time the amount of theophylline removed was measured in the total collected spent dialysate, after a 3.75 hour hemodialysis and an 8 hour extended dialysis.
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Asymmetric dimethylarginine in response to recombinant tissue-type plasminogen activator and erythropoietin in acute stroke.
Stroke
PUBLISHED: 06-20-2013
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In the German Multicenter Erythropoietin (EPO) Stroke Trial, patients not receiving thrombolysis most likely benefited from EPO on clinical recovery, whereas a combination of rtPA and EPO was associated with increased mortality. We investigated whether the combination of rtPA and EPO increased release of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA), and thereby potentially deteriorated ischemic stroke outcome, as suggested from experimental data.
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Serum neutrophil gelatinase-associated lipocalin (NGAL) in patients with Shiga toxin mediated haemolytic uraemic syndrome (STEC-HUS).
Thromb. Haemost.
PUBLISHED: 05-13-2013
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Neutrophil gelatinase-associated lipocalin (NGAL) is an increasingly used biomarker for acute kidney injury (AKI). Its utility in adult patients with AKI caused by Shiga toxin producing Escherichia coli infection (STEC)-associated haemolytic-uraemic syndrome (HUS), remains unknown. We aimed to evaluate the prognostic value of serum NGAL admission levels for the need of renal replacement therapy (RRT) in STEC-HUS patients. Baseline serum NGAL was determined by ELISA in 39 patients with STEC O104:H4 infection cared for at Hannover Medical School during the outbreak in Germany through May-July 2011. Patients with HUS had significant higher NGAL levels than healthy controls (379 [248 - 540] vs 39.0 [37.5-45] ng/ml, p < 0.0001). During clinical course, 24 patients required RRT at a median of five days after admission. NGAL admission levels were higher in patients requiring RRT (476 (344-639) ng/ml) compared to patients not requiring RRT (257 (196-426) ng/ml; p < 0.001). Unadjusted and adjusted logistic regression analyses identified NGAL as an independent predictor for need of RRT. In a combined model, a joint NGAL/AKIN classification approach improved the predictive accuracy for need of RRT over either marker alone. The combined categorical cut-off point defined by NGAL ? 330 ng/ml and presence of AKI (AKIN ? I) on admission correctly identified 20 of 24 patients requiring RRT (odds ratio 20, sensitivity 83%, specificity 80%, negative predictive value 75%, positive predictive value 87%). NGAL may serve as an adjunctive tool to improve risk prediction in patients with STEC-HUS.
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Tissue concentration of paraquat on day 32 after intoxication and failed bridge to transplantation by extracorporeal membrane oxygenation therapy.
BMC Pharmacol Toxicol
PUBLISHED: 04-10-2013
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Paraquat is a highly toxic herbicide, which not only leads to acute organ damage, but also to pulmonary fibrosis. There are only anecdotal reports of rescue lung transplantation, as paraquat is stored and only slowly released from different tissues. Bridging the time to complete depletion of paraquat from the body could render this exceptional therapy strategy possible, but not much is known on the time interval after which transplantation can safely be performed.
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Cotrimoxazole plasma levels, dialyzer clearance and total removal by extended dialysis in a patient with acute kidney injury: risk of under-dosing using current dosing recommendations.
BMC Pharmacol Toxicol
PUBLISHED: 03-20-2013
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Dosing of antibiotics in critically ill patients is challenging. It becomes even more difficult if renal or hepatic impairment ensue. Modern means of renal replacement therapy are capable of removing antibiotics to a higher rate than decades ago, leaving clinicians with a high degree of uncertainty concerning the dose of antibiotics in this patient population. Cotrimoxazole, a combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is frequently used in the treatment of several infections including Pneumocystis jirovecii pneumonia (PCP).
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Quantitative MRI shows cerebral microstructural damage in hemolytic-uremic syndrome patients with severe neurological symptoms but no changes in conventional MRI.
Neuroradiology
PUBLISHED: 03-18-2013
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Severe neurological symptoms in Shiga toxin-producing Escherichia coli infection associated hemolytic-uremic syndrome (STEC-HUS) are often accompanied by none or only mild alterations of cerebral magnetic resonance imaging (MRI). This study aims to analyze if quantitative MRI is able to reveal cerebral pathological alterations invisible for conventional MRI.
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Comprehensive analysis of glomerular mRNA expression of pro- and antithrombotic genes in atypical haemolytic-uremic syndrome (aHUS).
Virchows Arch.
PUBLISHED: 02-15-2013
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Atypical haemolytic-uremic syndrome (aHUS) is, in most cases, due to hereditary or acquired defects in complement regulation and a life-threatening disease. Despite the rapidly grown knowledge about the primary defects in aHUS, the pathogenesis that links complement dysregulation with microthrombus formation in aHUS is still unknown. Thus, we examined the glomerular microvascular expression of pro- and antithrombotic genes. Glomeruli were microdissected from 12 archival paraffin-embedded biopsies with aHUS and from seven control biopsies. Glomerular mRNA expression was quantified by single real-time PCR reactions after preamplification. In addition immunostains were performed for plasminogen activator inhibitor 1 (PAI-1) and for tissue plasminogen activator (tPA). Results were compared between cases and controls and with clinical data. Glomeruli in aHUS had increased mRNA expression of antifibrinolytic, prothrombotic PAI-1, antithrombotic thrombomodulin (THBD) and CD73 and decreased expression of profibrinolytic, antithrombotic tPA compared to controls. Impaired fibrinolysis due to increased microvascular expression of the antifibrinolytic PAI-1 in combination with the decreased expression of the profibrinolytic tPA seems to be a final common pathway in renal thrombotic microangiopathy that is also effective in aHUS. The concomitant induction of antithrombotic transcripts likely indicates counterregulatory efforts, demonstrating that the capillary bed is not a passive victim of complement attack. Future research should investigate if and how complement activation could induce the reported shift in the expression of PAI-1 and tPA.
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Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice.
Nephrol. Dial. Transplant.
PUBLISHED: 01-04-2013
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Symmetrical dimethylarginine (SDMA), the structural isomer of the nitric oxide synthase inhibitor asymmetrical dimethylarginine, has long been regarded as an inert substance. Recent epidemiological and preclinical data suggest that it might be involved in the pathophysiology of renal and cardiovascular diseases. Therefore, we aimed to investigate the effect of chronic SDMA infusion on renal and cardiac function in mice.
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Effect of isovolemic, isothermic hemodialysis on cerebral perfusion and vascular stiffness using contrast computed tomography and pulse wave velocity.
PLoS ONE
PUBLISHED: 01-02-2013
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Patients undergoing hemodialysis treatment have a six-fold increased risk for stroke relative to the general population. However, the effect of hemodialysis on cerebral blood flow is poorly studied and confounding factors like blood pressure and ultrafiltration as well as temperature changes have rarely been accounted for. The aim of our study was to use state-of-the-art technology to evaluate the effect of a single dialysis session on cerebral perfusion as well as on vascular stiffness.
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Angiopoietin-2 in adults with congenital heart disease and heart failure.
PLoS ONE
PUBLISHED: 01-01-2013
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Chronic heart failure is an important cause for morbidity and mortality in adults with congenital heart disease (ACHD). While NT-proBNP is an established biomarker for heart failure of non-congenital origin, its application in ACHD has limitations. The angiogenic factors Angiopoietin-1 and -2 (Ang-1, Ang-2), vascular endothelial growth factor (VEGF), and soluble receptor tyrosine kinase of the Tie family (sTie2) correlate with disease severity in heart failure of non-congenital origin. Their role in ACHD has not been studied.
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Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease.
Nephrol. Dial. Transplant.
PUBLISHED: 11-29-2011
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Thermal sensitivity in uraemia is decreased. Non-selective synthetic nitric oxide synthase (NOS) inhibitors significantly attenuate thermal hyperalgesia in preclinical models. The aim of our study was to evaluate the effect of experimental uraemia, which is associated with an increase of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), on thermal sensitivity in rats. Furthermore, we intended to study the effect of chronic ADMA infusion alone on thermal sensitivity.
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Pathogenic cycle between the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine and the leukocyte-derived hemoprotein myeloperoxidase.
Circulation
PUBLISHED: 11-14-2011
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The nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) and the leukocyte-derived hemoprotein myeloperoxidase (MPO) are associated with cardiovascular diseases. Activation of monocytes and polymorphonuclear neutrophils (PMNs) with concomitant release of MPO is regulated in a nitric oxide-dependent fashion. The aim of the study was to investigate a potential 2-way interaction between ADMA and MPO.
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High-dose erythropoietin has no effect on short- or long-term graft function following deceased donor kidney transplantation.
Kidney Int.
PUBLISHED: 10-19-2011
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We evaluated short- and long-term effects of high-dose recombinant human erythropoietin (rHuEPO) in kidney transplantation in a prospective double-blind, placebo-controlled study. Patients with chronic kidney disease following receipt of a deceased donor kidney allograft were randomized to 3 doses of 40,000 units rHuEPO or placebo. The primary study end point was kidney function 6 weeks after transplantation with secondary end points of incidence of delayed graft function and kidney function 12 months after transplantation. Six weeks or 12 months after transplantation, the difference between estimated glomerular filtration rates was not significant comparing 44 patients who received rHuEPO to 44 patients receiving placebo. There was no significant difference regarding the incidence of delayed graft function (10 of 44 with rHuEPO compared with 14 of 44 on placebo). Protocol biopsies at 6 weeks and 6 months post transplant showed no significant differences in all assessed histological indices. The number and severity of adverse events were comparable between groups, as was patient and graft survival after 12 months. Thus, treatment with high-dose rHuEPO after kidney transplantation, although well tolerated, had no effect on long-term graft function or histology.
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Angiopoietin-2 levels predict mortality in CKD patients.
Nephrol. Dial. Transplant.
PUBLISHED: 10-04-2011
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The pathophysiology of aggravated atherosclerosis in chronic kidney disease (CKD) is still incompletely understood. However, there is an increasing focus on non-traditional risk factors, including endothelial dysfunction. Angiopoietin-2 (Ang-2) impairs endothelial function by inhibiting the binding of Angiopoietin-1 (Ang-1) to their shared receptor Tie2 and is increased in diabetes, hypertension, coronary heart disease and CKD. Furthermore, Ang-2 levels are associated with the prevalent vascular burden of CKD patients. Thus, we aimed to investigate its impact on outcome in CKD, the population most likely to die of cardiovascular events.
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Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO).
Kidney Int.
PUBLISHED: 09-14-2011
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Drug dosage adjustment for patients with acute or chronic kidney disease is an accepted standard of practice. The challenge is how to accurately estimate a patients kidney function in both acute and chronic kidney disease and determine the influence of renal replacement therapies on drug disposition. Kidney Disease: Improving Global Outcomes (KDIGO) held a conference to investigate these issues and propose recommendations for practitioners, researchers, and those involved in the drug development and regulatory arenas. The conference attendees discussed the major challenges facing drug dosage adjustment for patients with kidney disease. In particular, although glomerular filtration rate is the metric used to guide dose adjustment, kidney disease does affect nonrenal clearances, and this is not adequately considered in most pharmacokinetic studies. There are also inadequate studies in patients receiving all forms of renal replacement therapy and in the pediatric population. The conference generated 37 recommendations for clinical practice, 32 recommendations for future research directions, and 24 recommendations for regulatory agencies (US Food and Drug Administration and European Medicines Agency) to enhance the quality of pharmacokinetic and pharmacodynamic information available to clinicians. The KDIGO Conference highlighted the gaps and focused on crafting paths to the future that will stimulate research and improve the global outcomes of patients with acute and chronic kidney disease.
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Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial.
Lancet
PUBLISHED: 09-02-2011
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In May 2011, an outbreak of Shiga toxin-producing enterohaemorrhagic E coli O104:H4 in northern Germany led to a high proportion of patients developing post-enteritis haemolytic uraemic syndrome and thrombotic microangiopathy that were unresponsive to therapeutic plasma exchange or complement-blocking antibody (eculizumab). Some patients needed ventilatory support due to severe neurological complications, which arose 1 week after onset of enteritis, suggesting an antibody-mediated mechanism. Therefore, we aimed to assess immunoadsorption as rescue therapy.
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The German Chronic Kidney Disease (GCKD) study: design and methods.
Nephrol. Dial. Transplant.
PUBLISHED: 08-22-2011
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Chronic kidney disease (CKD) is increasingly recognized as a global health problem. The conditions leading to CKD, the health impact of CKD and the prognosis differ markedly between affected individuals. In particular, renal failure and cardiovascular mortality are competing risks for CKD patients. Opportunities for targeted intervention are very limited so far and require an improved understanding of the natural course of CKD, of the risk factors associated with various clinical end points and co-morbidities as well as of the underlying pathogenic mechanisms.
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Unilateral nephrectomy causes an abrupt increase in inflammatory mediators and a simultaneous decrease in plasma ADMA: a study in living kidney donors.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 08-10-2011
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Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases (NOS). Reducing inducible NOS activity in acute inflammation seems to be desirable. In vitro data show that ADMA increases in response to inflammatory mediators, yet the effect of acute inflammation in vivo is scarcely studied. The aim of the study was to evaluate ADMA plasma levels before, during, and after the acute (nonbacterial) inflammatory-like state. Plasma ADMA, l-arginine, C-reactive protein, and IL-6 were determined in 24 healthy subjects undergoing living related kidney donation before as well as 1, 6, 12, 24, 72, and 168 h thereafter. Six hours after nephrectomy, ADMA levels decreased compared with baseline (0.488 ± 0.075 vs. 0.560 ± 0.060 ?mol/l, P < 0.05). This difference became even more marked 24 h after the operation (0.478 ± 0.083 ?mol/l, P < 0.01 vs. baseline), when the proinflammatory cytokine IL-6 peaked. Seven days after unilateral nephrectomy, ADMA levels were elevated above baseline (0.63 ± 0.05 ?mol/l, P < 0.001 vs. baseline). l-Arginine levels decreased already 1 h after nephrectomy (97.5 ± 22.5 ?mol/l, P < 0.01 vs. baseline) and paralleled the change in ADMA thereafter. At the end of the observation period when inflammation markers were regressing, l-arginine levels were significantly elevated above baseline (160.6 ± 25.1 ?mol/l, P < 0.001 vs. baseline). In summary, this is the first study showing that both ADMA and l-arginine decrease temporarily after unilateral nephrectomy coinciding with the increase in inflammatory mediators. The l-arginine/ADMA ratio, a surrogate for NO production capacity, was only altered for <24 h.
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ABO-incompatible renal transplantation: From saline flushes to antigen-specific immunoadsorption-Tools to overcome the barrier.
Korean J Hematol
PUBLISHED: 08-09-2011
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On April 23, 1951, a 30-year-old woman received the first intentional ABOi (ABO incompatible) renal transplantation in Boston. At that time, it was commonly believed that intensely rinsing the graft to remove blood would be sufficient to overcome any immunological problems associated with blood type incompatibility. However, when the abovementioned patient and another ABOi transplant recipient died within a month, Humes and colleagues arrived at the same conclusion: "We do not feel that renal transplantation in the presence of blood incompatibility is wise." In the decades that followed, we learned that the oligosaccharide surface antigens representing the ABO-blood group antigens are expressed not only on erythrocytes but also on cells from various tissues, including the vascular endothelium. The growing gap between organ demand and availability has sparked efforts to overcome the ABO barrier. After its disappointing results in the early 1970s, Japan became the leader of this endeavor in the 1980s. All protocols are based on 2 strategies: removal of preformed antibodies with extracorporeal techniques and inhibition of ongoing antibody production. Successful ABOi renal transplantation became possible with the advent of splenectomy, new immunosuppressive drugs (e.g., rituximab, a monoclonal antibody against CD20), and extracorporeal methods such as antigen-specific immunoadsorption. This review summarizes the underlying pathophysiology of ABOi transplantation and the different protocols available. Further, we briefly touch potential short- and long-term problems, particularly the incidence of infectious complications and malignancies, that can arise with high-intensity immunosuppressive therapy.
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Quantitative analysis of the antifungal drug anidulafungin by LC-online SPE-MS/MS in human plasma.
Biomed. Chromatogr.
PUBLISHED: 07-07-2011
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The objective of this study was to develop a fast and robust method for the quantitation of the antifungal drug anidulafungin in human plasma samples by generic two-dimensional liquid chromatography (online-SPE/reversed phase LC) coupled to a tandem-quadrupole mass spectrometer (LC-online SPE-MS/MS). Online SPE was performed using an Oasis HLB cartridge column and for reversed-phase chromatography a Nucleodur Gravity C(18) column was used. A 100 ?L aliquot of human plasma was extracted with 200 ?L of 80:20 MeOH-0.2 M ZnSO(4) (v/v) as precipitation reagent containing ascomycin as internal standard (IS). The supernatant was directly injected for analysis. The total run time was 4.5 min. Anidulafungin and ascomycin were detected in the positive ionization mode. The method performance data for anidulafungin, such as limit of detection (0.013 µg/mL), lower limit of quantitation (0.04 µg/mL), linearity (R(2) = 0.9999) and concentration range (0.04-10 µg/mL) were ascertained. Intra- and inter-day precisions were ?6.6% and intra- and inter-day accuracies were 98.5-101.0 and 100.0-102.5%, respectively. The assay was successfully applied for quantitation of anidulafungin in patient plasma samples.
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Chronic renal failure alters endothelial function in cerebral circulation in mice.
Am. J. Physiol. Heart Circ. Physiol.
PUBLISHED: 06-24-2011
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We examined structure, composition, and endothelial function in cerebral arterioles after 4 wk of chronic renal failure (CRF) in a well-defined murine model (C57BL/6J and apolipoprotein E knockout female mice). We also determined quantitative expression of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (on serine 1177 and threonine 495), and caveolin-1; quantitative expression of markers of vascular inflammation or oxidative stress [Rock-1, Rock-2, VCAM-1, and peroxisome proliferator-activated receptor-? (PPAR?)]; and the plasma concentration of L-arginine and asymmetric dimethylarginine (ADMA). Our hypothesis was that endothelial function would be impaired in cerebral arterioles during CRF following either a decrease in NO production (through alteration of eNOS expression or regulation) or an increase in NO degradation (due to oxidative stress or vascular inflammation). Endothelium-dependent relaxation was impaired during CRF, but endothelium-independent relaxation was not. CRF had no effect on cerebral arteriolar structure and composition. Quantitative expressions of eNOS, eNOS phosphorylated on serine 1177, caveolin-1, Rock-1, Rock-2, and VCAM-1 were similar in CRF and non-CRF mice. In contrast, quantitative expression of PPAR? (which exercises a protective role on blood vessels) was significantly lower in CRF mice, whereas quantitative expression of eNOS phosphorylated on the threonine 495 (the inactive form of eNOS) was significantly higher. Lastly, the plasma concentration of ADMA (a uremic toxin and an endogenous inhibitor of eNOS) was elevated and plasma concentration of L-arginine was low in CRF. In conclusion, endothelial function is impaired in a mouse model of early stage CRF. These alterations may be related (at least in part) to a decrease in NO production.
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Circulating miR-210 predicts survival in critically ill patients with acute kidney injury.
Clin J Am Soc Nephrol
PUBLISHED: 06-23-2011
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MicroRNAs (miRNAs) are small ribonucleotides regulating gene expression. MicroRNAs are present in the blood in a remarkably stable form. We tested whether circulating miRNAs in the plasma of critically ill patients with acute kidney injury (AKI) at the inception of renal replacement therapy are deregulated and may predict survival.
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High plasma dimethylarginine levels are associated with adverse clinical outcome after stroke.
J. Atheroscler. Thromb.
PUBLISHED: 05-12-2011
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Increased levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, have been observed in patients with cardiovascular risk factors and atherosclerosis and in patients with a history of stroke. The role of ADMA and its analogue symmetric dimethylarginine (SDMA) in acute ischemic stroke is yet unclear. We hypothesized that plasma dimethylarginine levels increase in the hyper-acute phase after ischemic stroke and that their time course is related to stroke outcome.
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Dosing of antibiotics in critically ill patients undergoing renal replacement therapy.
Curr Pharm Biotechnol
PUBLISHED: 05-11-2011
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On September 11, 1945 Maria Schafstaat was the first patient who successfully underwent a dialysis treatment for acute kidney injury (AKI), formerly known as acute renal failure. Since then, the number of patients with AKI is increasing worldwide. Today AKI is generally one feature of a multiple organ dysfunction syndrome (MODS), which develops in response to major surgery, cardiogenic shock or sepsis. Several clinical studies have shown that early and appropriate antibiotic therapy in those patients is of utter importance, yet it remains one of the most difficult challenges to meet. Even in critically ill patients with conserved renal function a myriad of pathophysiological changes, resulting in increased volume of distribution, decreased protein binding and altered hepatic drug clearance, makes appropriate antibiotic dosin difficult. Adequate pharmacotherapy, i.e. dose of anti-infective agens is becoming even more complicated if it has to be tailored to counteract their removal by different modes and intensities of renal replacement therapy. This review summarizes our sparse knowledge about pharmacokinetic studies and dosing recommendations of drugs in patients with AKI undergoing continuous renal replacement therapies (CRRTs) such as continuous venovenous hemofiltration (CVVH) as well as extended dialysis (ED), an increasingly used method to treat patients with AKI in the intensive care setting. We reflect on failure of several large prospective controlled studies to show a survival benefit of higher doses of renal replacement therapy, a finding that might be caused by the fact that we still adhere to dosing guidelines for antibiotics which are at best ineffectual but might also lead to potentially dangerous underdosing of these life saving drugs. Lastly we address possible strategies to overcome the lack of knowledge, the lack of data and the lack of interest in this important area of critical care medicine. Improvement of clinical outcomes and reduction of antibiotic resistance in this patient population will require nephrologist, intensivists and pharmacists to work together.
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Immunoadsorption therapy for steroid-unresponsive relapses in patients with multiple sclerosis.
Blood Purif.
PUBLISHED: 04-27-2011
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Therapeutic plasma exchange (TPE) in steroid-unresponsive relapses of patients with multiple sclerosis (MS) is an established therapy with response rates of up to 70%. Immunoadsorption (IA) specifically removes immunoglobulins from the patients plasma. It is hypothesized that IA therapy might be better tolerated than and as effective as TPE in the treatment of MS relapses. Experiences with IA therapy of steroid-unresponsive MS relapses are limited.
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Combination of everolimus with calcineurin inhibitor medication resulted in post-transplant haemolytic uraemic syndrome in lung transplant recipients--a case series.
Nephrol. Dial. Transplant.
PUBLISHED: 02-10-2011
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Post-transplant haemolytic uraemic syndrome (HUS) is a rare but serious disease with a high mortality rate, when left untreated. Immunosuppressive drugs like calcineurin inhibitors as well as mammalian target of rapamycin inhibitors have been reported as causative agents for post-transplant HUS.
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Conversion from conventional in-centre thrice-weekly haemodialysis to short daily home haemodialysis ameliorates uremia-associated clinical parameters.
Int Urol Nephrol
PUBLISHED: 02-09-2011
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Under physiological conditions, kidneys work continuously, 168 h/week. In contrast, patients with end-stage renal disease are usually dialysed only 12 h/week. Even if considered adequate by current Kt/V-based dose estimates, this unphysiological dose is associated with an unacceptable annual mortality rate of 10-20%. Increasing dialysis dose might ameliorate this mortality rate.
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Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection.
Crit Care
PUBLISHED: 02-08-2011
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Virus-associated hemophagocytic syndrome (VAHS) is a severe complication of various viral infections often resulting in multiorgan failure and death. The purpose of this study was to describe baseline characteristics, development of VAHS, related treatments and associated mortality rate of consecutive critically ill patients with confirmed 2009 influenza A (H1N1) infection and respiratory failure.
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High permeability dialysis membrane allows effective removal of myoglobin in acute kidney injury resulting from rhabdomyolysis.
Crit. Care Med.
PUBLISHED: 02-08-2011
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The objective of this study was to test the ability of myoglobin removal of a novel, high-permeability polysulphone dialyzer in acute kidney injury as a result of rhabdomyolysis.
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TLR-4+ peripheral blood monocytes and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study.
Nephrol. Dial. Transplant.
PUBLISHED: 01-14-2011
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Atherosclerosis is an inflammatory process mediated by circulating immune cells, including monocytes. There is accumulating evidence for the involvement of Toll-like receptor 4 (TLR-4) as a mediator of atherogenesis.
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Effect of acute kidney injury requiring extended dialysis on 28 day and 1 year survival of patients undergoing interventional lung assist membrane ventilator treatment.
BMC Nephrol
PUBLISHED: 01-03-2011
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Extracorporeal lung assist devices are increasingly used in the intensive care unit setting to improve extracorporeal gas exchange mainly in patients with acute respiratory distress syndrome. ARDS is frequently accompanied by acute kidney injury; however it is so far unknown how the combination of these two conditions affects long term survival of critically ill patients.
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Symmetrical and asymmetrical dimethylarginine as predictors for mortality in patients referred for coronary angiography: the Ludwigshafen Risk and Cardiovascular Health study.
Clin. Chem.
PUBLISHED: 10-29-2010
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Asymmetrical dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, has been linked to cardiovascular risk. The clinical role of its structural isomer symmetrical dimethylarginine (SDMA) remains largely unclear.
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Symmetrical dimethylarginine outperforms CKD-EPI and MDRD-derived eGFR for the assessment of renal function in patients with adult congenital heart disease.
Kidney Blood Press. Res.
PUBLISHED: 08-28-2010
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Adults with congenital heart disease exhibit a 3-fold higher mortality in the presence of chronic kidney disease, hence assessment of renal function is crucial in this patient population. Formulas for the estimation of glomerular filtration rate (GFR) have not been evaluated in this patient population. Therefore, this study compares different markers and equations for the estimation of renal function in adults with congenital heart disease.
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Osteopontin predicts survival in critically ill patients with acute kidney injury.
Nephrol. Dial. Transplant.
PUBLISHED: 08-23-2010
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The cytokine osteopontin is involved in the pathophysiology of experimental acute kidney injury. We have tested the hypothesis that osteopontin levels might serve as a biomarker predicting outcome in critically ill patients requiring renal replacement therapy after acute kidney injury.
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SDMA is an early marker of change in GFR after living-related kidney donation.
Nephrol. Dial. Transplant.
PUBLISHED: 07-09-2010
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Early detection of changes in the glomerular filtration rate (GFR) is crucial in detecting acute kidney injury. There is burgeoning evidence from preclinical and clinical studies that symmetrical dimethylarginine (SDMA) correlates well with different parameters of renal function. In some studies, SDMA even outperformed creatinine as a marker of GFR. It is however unknown how fast SDMA is increasing after reduction in GFR. The aim of our study was therefore to determine the temporal change of SDMA in comparison with cystatin C after a defined reduction in GFR.
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Circulating levels of osteopontin are closely related to glomerular filtration rate and cardiovascular risk markers in patients with chronic kidney disease.
Eur. J. Clin. Invest.
PUBLISHED: 05-22-2010
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The pleiotropic cytokine osteopontin (OPN) is thought to be involved in the pathogenesis of atherosclerosis. However, the relationship between OPN and renal function, a cardiovascular risk factor itself, is not known. Therefore, we assessed the relationship between OPN plasma levels and renal function in patients at different stages of chronic kidney disease (CKD).
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Asymmetric dimethylarginine correlates with measures of disease severity, major adverse cardiovascular events and all-cause mortality in patients with peripheral arterial disease.
Vasc Med
PUBLISHED: 05-19-2010
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Peripheral arterial disease (PAD) is associated with major cardiovascular morbidity and mortality. Abnormalities in nitric oxide metabolism due to excess of the NO synthase inhibitor asymmetric dimethylarginine (ADMA) may be pathogenic in PAD. We explored the association between ADMA levels and markers of atherosclerosis, function, and prognosis. A total of 133 patients with symptomatic PAD were enrolled. Ankle-brachial index (ABI), walking time, vascular function measures (arterial compliance and flow-mediated vasodilatation) and plasma ADMA level were assessed for each patient at baseline. ADMA correlated inversely with ABI (r = -0.238, p = 0.003) and walking time (r = -0.255, p = 0.001), independent of other vascular risk factors. We followed up 125 (94%) of our 133 initial subjects with baseline measurements (mean 35 months). Subjects with ADMA levels in the highest quartile (> 0.84 mumol/l) showed a significantly greater occurrence of a major adverse cardiovascular event (MACE) compared to those with ADMA levels in the lower three quartiles (p = 0.001). Cox proportional-hazards regression analysis revealed that ADMA was a significant predictor of MACE, independent of other risk factors including age, sex, blood pressure, smoking history, diabetes and ABI (hazard ratio = 5.1, p < 0.001). Measures of vascular function, such as compliance, flow-mediated vasodilatation (FMVD) and blood pressure, as well as markers of PAD severity, including ABI and walking time, were not predictive. In conclusion, circulating levels of ADMA correlate independently with measures of disease severity and major adverse cardiovascular events. Agents that target this pathway may be useful for this patient population. Clinical Trial Registration - URL: http:// www.clinicaltrials.gov. Unique identifier: NCT00284076.
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Back to the future: extended dialysis for treatment of acute kidney injury in the intensive care unit.
J. Nephrol.
PUBLISHED: 05-18-2010
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On September 11, 1945, Maria Schafstaat was the first patient who successfully underwent a dialysis treatment for acute kidney injury (AKI). The ingenious design of the first dialysis machine, made of cellophane tubing wrapped around a cylinder that rotated in a bath of fluid, together with the brave determination to treat patients with AKI, enabled the Dutch physician W.J. Kolff to save the life of the 67-year-old woman. By treating her for 690 minutes (i.e., 11.5 hours) with a blood flow rate of 116 ml/min, Kolff also set the coordinates of a renal replacement therapy that has enjoyed an unsurpassed renaissance over the last decade for treatment of severely ill patients with AKI in the intensive care unit (ICU). Prolonged dialysis time with low flow rates - these days, called extended dialysis (ED) - combines several advantages of both intermittent and continuous techniques, which makes it an ideal treatment method for ICU patients with AKI. This review summarizes our knowledge of this method, which is increasingly used in many centers worldwide. We reflect on prospective controlled studies in critically ill patients that have documented that small-solute clearance with ED is comparable with that of intermittent hemodialysis and continuous venovenous hemofiltration, as well as on studies showing that patients cardiovascular stability during ED is similar to that with continuous renal replacement therapy. Furthermore, we report on logistic and economic advantages of this method. We share our view on how extended dialysis offers ample opportunity for a collaborative interaction between nephrologists and intensivists as the nephrology staff, enabling optimal treatment of complex critically ill patients by using the skill and knowledge of 2 indispensable specialties in the ICU. Lastly, we address the problem of ED intensity, which does not seem to have an impact on survival at higher doses, a finding that might be caused by the fact that we still adhere to dosing guidelines for antibiotics which are at best ineffectual but might also lead to potentially dangerous underdosing of these life-saving drugs.
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[Allopurinol-induced hypersensitivity syndrome resulting in death].
Med. Klin. (Munich)
PUBLISHED: 05-11-2010
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The present report describes the case of a 67-year-old patient who developed an allopurinol-induced hypersensitivity syndrome (AHS) with toxic epidermal necrolysis and subsequently died of septic multiorgan failure. Considering the increasing prescription rate of allopurinol, the present case report intends to demonstrate the underestimated threat of AHS.
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Removal of asymmetric dimethylarginine during artificial liver support using fractionated plasma separation and adsorption.
Scand. J. Gastroenterol.
PUBLISHED: 05-06-2010
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Asymmetric dimethylarginine (ADMA) is the most potent endogenous nitric oxide synthase inhibitor. Elevated ADMA levels have been linked to increased mortality in different patient populations. Key regulation of ADMA levels mainly takes place in the liver. Hence, ADMA is elevated in liver disease. There is no specific pharmacological treatment to lower the elevated ADMA levels. Hemodialysis is of limited efficiency in removing ADMA as it is highly protein bound. Prometheus is an extracorporeal liver support system which allows the removal of protein-bound toxins. We assessed the efficiency of the Prometheus system in reducing high ADMA levels in patients with liver failure.
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Endothelial progenitor cells and cardiovascular events in patients with chronic kidney disease--a prospective follow-up study.
PLoS ONE
PUBLISHED: 04-23-2010
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Endothelial progenitor cells (EPCs) mediate vascular repair and regeneration. Their number in peripheral blood is related to cardiovascular events in individuals with normal renal function.
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Removal of elevated circulating angiopoietin-2 by plasma exchange--a pilot study in critically ill patients with thrombotic microangiopathy and anti-glomerular basement membrane disease.
Thromb. Haemost.
PUBLISHED: 02-22-2010
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In critically ill patients, the massive release of angiopoietin-2 (Ang-2) from Weibel-Palade bodies interferes with protective angiopoietin-1 (Ang-1)/Tie2 signalling in endothelial cells, thus leading to vascular inflammation and subsequent organ-dysfunction. We hypothesised that plasma exchange (PE) is efficient for lowering excess Ang-2 levels in critically ill patients with thrombocytic microangiopathy (TMA) or anti-glomerular basement membrane (anti-GBM) disease. Plasma Ang-1 and Ang-2 were measured by immuno-luminometric assays in patients with TMA (n=9) or anti-GBM disease (n=4) before and after up to four PE sessions. Twenty apparently healthy volunteers served as controls. Median (IQR) plasma levels of Ang-2 were markedly increased in patients with TMA (7.3 (2.4-21.1) ng/ml) and anti-GBM disease (5.8 (3.4-7.0) ng/ml) compared to healthy controls (1.0 (0.9-1.4) ng/ml, p <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.62-1.62) ng/ml) and anti-GBM disease patients (0.74 (0.59-3.62) ng/ml) compared to healthy controls (2.5 (1.93-3.47) ng/ml, p <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7 ± 19.6% per treatment (p <0.0001), whereas low Ang-1 plasma levels remained unchanged (0.3 ± 58.5%; p=0.147). Ang-2 levels declined to almost normal values during ?4 PE treatments (Friedman´s test p<0.0001). PE is an effective method to remove excess circulating Ang-2. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity.
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Circulating angiopoietin-2 levels increase with progress of chronic kidney disease.
Nephrol. Dial. Transplant.
PUBLISHED: 02-22-2010
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Angiopoietin-2 (Ang-2) is an antagonistic ligand of the endothelial-specific Tie2 receptor. Patients on dialysis have markedly elevated Ang-2 levels, and those correlate with their atherosclerotic burden. The aim of the current study was to investigate the relationship between the circulating levels of Ang-2 and renal function throughout all stages of chronic kidney disease (CKD). In addition, we aimed to detect a potential link between the nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) and the Ang-2 levels.
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Serum neutrophil gelatinase-associated lipocalin at inception of renal replacement therapy predicts survival in critically ill patients with acute kidney injury.
Crit Care
PUBLISHED: 02-01-2010
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Neutrophil gelatinase-associated lipocalin (NGAL) is a promising novel biomarker that correlates with the severity and outcome of acute kidney injury (AKI). However, its prognostic utility during the late course of AKI, especially in patients that require renal replacement therapy (RRT) remains unknown. The aim of this study was to evaluate the predictive value of serum NGAL in patients with established AKI at inception of RRT in the intensive care unit (ICU).
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Biopsy proven acute interstitial nephritis after treatment with moxifloxacin.
BMC Nephrol
PUBLISHED: 01-21-2010
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Acute interstitial nephritis (AIN) is an important cause of reversible acute kidney injury. At least 70% of AIN is caused by various drugs, mainly penicillins and non-steroidal anti-inflammatory drugs. Quinolones are only rarely known to cause AIN and so far cases have been mainly described with older fluoroquinolones.
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Dosing of daptomycin in intensive care unit patients with acute kidney injury undergoing extended dialysis--a pharmacokinetic study.
Nephrol. Dial. Transplant.
PUBLISHED: 12-22-2009
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Daptomycin is a new intravenous cyclic lipopeptide antibiotic, licensed for the treatment of complicated skin and soft tissue infections caused by Gram-positive organisms including both susceptible and resistant strains of Staphylococcus aureus and for the treatment of various infections due to susceptible organisms, including serious and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis with associated bacteremia. Currently, no dosing recommendations exist for this drug for patients with acute kidney injury (AKI) undergoing renal replacement therapy. The aim of this study was to evaluate pharmacokinetics of daptomycin in critically ill patients with AKI undergoing extended dialysis (ED), a frequently used mean of renal replacement therapies in intensive care units (ICUs) around the world. Patients and methods. A prospective, single-dose pharmacokinetic study was performed in the medical and surgical ICUs of a tertiary care center. The aim was to investigate critically ill patients with anuric AKI being treated with ED and receiving daptomycin (n = 10). Daptomycin (6 mg/kg) was administered 8 h before ED was started.
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Asymmetric dimethylarginine and symmetric dimethylarginine: axis of evil or useful alliance?
Semin Dial
PUBLISHED: 08-28-2009
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Almost 40 years ago, in 1970, Kakimoto and Akazawa were the first to isolate and describe N-N, N-G- and N-G,N-G-dimethyl-arginine from human urine. Today, these substances are known as asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). In their detailed and meticulous publication, Kakimoto and Akazawa speculated about these two compounds: "They may have functional importance in proteins in which they are formed. If they are excreted into the urine as metabolites of body proteins, amounts of these substances in human urine may reflect methylation rate of body proteins and their turnover rates and determination of these substances might be important for the study of various pathological states." The following decades proved them to be right. ADMA, the most potent endogenous nitric oxide synthase (NOS) inhibitor was first found to be elevated in hemodialysis patients. It has been shown to correlate with traditional and nontraditional cardiovascular risk factors. ADMA is also a strong predictor of cardiovascular events and death in both patients with chronic kidney disease (CKD, stage 2-5) and in the general population. Moreover, ADMA predicts the progression of CKD. SDMA, the structural isomer of ADMA, has been shown to be an excellent marker of renal function in human and animal studies. There is emerging evidence that SDMA might also be involved in inflammation and atherosclerosis although it is only thought to be a (weak) indirect inhibitor of NOS. There is burgeoning evidence that these two substances may indeed damage normal physiological functions, or interfere with physiological defense mechanisms in CKD, play a role in the progression of renal disease, induce uremic symptoms, and may even contribute to dialysis-related complications. Hence these compounds are considered uremic toxins. This review summarizes our current concept how these two compounds might play a crucial part in the pathophysiology of uremia, either alone or in their combination. We also allude to the potential physiological role these substances might have.
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Angiopoietin-2 in patients requiring renal replacement therapy in the ICU: relation to acute kidney injury, multiple organ dysfunction syndrome and outcome.
Intensive Care Med
PUBLISHED: 05-19-2009
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Endothelial activation has emerged as an early event in the pathogenesis of microcirculatory dysfunction, capillary leakage and multi-organ dysfunction syndrome (MODS). Angiopoietin-2 (Ang-2), a circulating antagonistic ligand of the endothelial-specific Tie2 receptor, has been identified as a non-redundant gatekeeper of endothelial activation. On the basis of our previous report demonstrating release of Ang-2 in endotoxemia and sepsis, we aimed to study the utility of Ang-2 to serve as an outcome-specific biomarker in patients requiring renal replacement therapy (RRT) in the intensive care unit (ICU).
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Angiotensin II receptor blocker and statins lower elevated levels of osteopontin in essential hypertension--results from the EUTOPIA trial.
Atherosclerosis
PUBLISHED: 05-03-2009
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Osteopontin is a pleiotropic cytokine that has been implicated as a key factor in the development of atherosclerosis, a major complication of hypertension. We have earlier shown that olmesartan reduces mediators of vascular inflammation in patients with hypertension and cardiovascular disease. We aimed at studying the effect of olmesartan and/or pravastatin on osteopontin plasma levels, and the association between vascular inflammation markers and osteopontin in hypertensive patients.
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Circulating angiopoietin-2 in essential hypertension: relation to atherosclerosis, vascular inflammation, and treatment with olmesartan/pravastatin.
J. Hypertens.
PUBLISHED: 04-25-2009
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Endothelial activation has emerged as an early event in the pathogenesis of cardiovascular disease. Angiopoietin-2 (Ang-2) has been identified as a nonredundant endothelial-specific facilitator of vascular responsiveness to inflammatory stimuli. We have earlier shown that angiotensin II receptor blocker (ARB) reduces mediators of vascular inflammation in hypertension and cardiovascular disease. We aimed at studying the effect of ARB and/or 3-hydroxy-3-methyl-glutaryl-CoA blockade on Ang-2 and the association between vascular inflammation markers and Ang-2 levels in hypertensive patients.
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Pharmacokinetics and dialysate levels of daptomycin given intravenously in a peritoneal dialysis patient.
Scand. J. Infect. Dis.
PUBLISHED: 04-07-2009
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In this report we present pharmacokinetic (Pk) data of daptomycin given intravenously in a peritoneal dialysis patient. Daptomycin plasma levels were within therapeutic range; however, half-life of the drug was prolonged compared to haemodialysis. Both plasma and dialysate levels were found to be consistently above the minimal inhibitory concentration for daptomycin sensitive strains.
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Angiopoietin 2 and cardiovascular disease in dialysis and kidney transplantation.
Am. J. Kidney Dis.
PUBLISHED: 03-05-2009
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Accelerated atherosclerosis in patients with chronic kidney disease (CKD) is still incompletely understood. Angiopoietin 1 (Ang-1) and Ang-2 are 55-kDa antagonistic nonredundant gatekeepers of endothelial activation and thus are potential important factors in accelerated atherosclerosis. We aimed to study: (1) angiopoietin levels in patients treated by means of dialysis and kidney transplantation, (2) the association of altered angiopoietin levels with atherosclerosis, and (3) changes in altered levels after renal transplantation.
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Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis.
Nephrol. Dial. Transplant.
PUBLISHED: 02-28-2009
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Extended (daily) dialysis (EDD) is an increasingly popular mode of renal replacement therapy in the ICU (intensive care unit) as it combines the advantages of intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT), i.e. excellent detoxification accompanied by cardiovascular tolerability. The aim of this study was to evaluate pharmacokinetics (PK) of ertapenem, the newest carbapenem with once-daily dosing, in critically ill patients with anuric acute renal failure (ARF) undergoing EDD. Patients and
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Procedure-related pulmonary hypertension in patients with hepatocellular carcinoma undergoing percutaneous ethanol injection--role of ethanol, hemolysis, asymmetric dimethylarginine, and the nitric oxide system.
Crit. Care Med.
PUBLISHED: 02-27-2009
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Local percutaneous tumor ablation with ethanol injection (PEI) under general anesthesia is an established therapy for patients with nonresectable hepatocellular carcinoma (HCC). There are reports of sudden hypotension immediately after PEI therapy, which was attributed to an acute increase in pulmonary vascular resistance. The aim of our study was to objectively confirm pulmonary hypertension by right heart catheterization and to evaluate biochemical markers with relevance to the pulmonary circulation.
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Plasma exchange therapy in steroid-unresponsive relapses in patients with multiple sclerosis.
Blood Purif.
PUBLISHED: 02-19-2009
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Plasma exchange (PE) is well established for conditions such as rapid progressive vasculitis associated with autoantibodies against neutrophil cytoplasmic antigens (ANCA), anti-glomerular basement membrane (GBM) antibody disease, or thrombotic thrombocytopenic purpura (TTP). Also, several neurological disorders, such as acute worsening in myasthenia gravis, Guillan-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), can successfully be treated with PE. Only small case series have previously shown that PE is also effective in relapses in patients with multiple sclerosis (MS).
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Risk of underdosing of ampicillin/sulbactam in patients with acute kidney injury undergoing extended daily dialysis--a single case.
Nephrol. Dial. Transplant.
PUBLISHED: 02-18-2009
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The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. The normal kidneys eliminate approximately 60% of ampicillin (371.39 Da) and sulbactam (255.22 Da). Concomitant with the decline in renal function, the terminal elimination half-life increases from 1 up to 24 h in patients with ESRD. Patients on three times weekly low flux haemodialysis exhibit a half-life of 2.3 h on and 17.4 h off dialysis. In contrast, in the present observation the elimination half-life in a single patient with acute kidney injury undergoing extended daily dialysis (EDD) with a polysulphone membrane was 1.5 h, indicating that the current dosing regimen for haemodialysis outpatients (ampicillin/sulbactam 2.0/1.0 g/day) would result in a significant underdosing for patients undergoing EDD.
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