Preoperative serum uric acid predicts incident acute kidney injury following cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) following cardiac surgery is a frequent complication and several risk factors increasing its incidence have already been characterized. This study evaluates the influence of preoperative increased serum uric acid (SUA) levels in comparison with other known risk factors on the incidence of AKI following cardiac surgery. METHODS: During a period of 5 month, 247 patients underwent elective coronary artery bypass grafting, valve replacement/ repair or combined bypass and valve surgery. Datas were prospectively analyzed. Primary endpoint was the incidence of AKI as defined by the AKI criteria comparing patients with preoperative serum uric acid (SUA) levels below versus above the median. Multivariate logistic regression analysis was used to identify independent predictors of postoperative AKI. RESULTS: Thirty (12.1%) of the 247 patients developed postoperative AKI, 24 of 30 (80%) had preoperative SUA- levels above the median (≥373 µmol/l) (OR: 4.680, CI 95% 1.840; 11.904, p = 0.001). In the multivariate analysis SUA levels above the median (OR: 5.497, CI 95% 1.772; 17.054, p = 0.003), cardiopulmonary bypass (CPB) time > 90 min (OR: 4.595, CI 95% 1.587; 13.305, p = 0.005), cardiopulmonary bypass (CPB) > 30 kg/m2 (OR: 3.208, CI 95% 1.202; 8.562; p = 0.02), and preoperative elevated serum-creatinine levels (OR: 1.015, CI 95% 1.001; 1.029, p = 0.04) were independently associated with postoperative AKI. CONCLUSIONS: Serum uric acid is an independent risk marker for AKI after cardiac surgery. From all evaluated factors it showed the highest odds ratio.

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

[Role of plasmapheresis and immunoadsorption in salvage therapy of rheumatological diseases]. / Rolle von Plasmapherese und Immunadsorption in der Rescue-Therapie rheumatologischer Erkrankungen.

Many rheumatological diseases are either caused by specific known proteins, such as antibodies or mediated by a plethora of cytokines. Both the unspecific immunosuppressive therapy and the specific action of biologics usually require time to be effective; therefore, extracorporeal forms of treatment are increasingly being employed in severe forms of rheumatological diseases as well as in patients who cannot tolerate pharmacological treatment or where the risk of pharmacological treatment may outweigh the potential benefits. Therapeutic plasma exchange (TPE) removes not only pathogenic substances, such as autoantibodies, lipoproteins and circulating immune complexes from the plasma but also cytokines. The removed plasma that is discarded has to be substituted by blood products, e.g. human albumin or fresh frozen plasma. Fresh frozen plasma is always used when missing plasma components must be replenished, such as ADAMTS-13 in thrombotic thrombocytopenic purpura (TTP). The separated plasma can be further processed by pumping into a hollow fiber filter (cut-off of ~700 kD) and in this way low-density lipoprotein cholesterol and IgM can be eliminated. This treatment mode, called cascade filtration is used to treat diseases, such as Waldenström's macroglobulinemia and cryoglobulinemia. A specific way to remove antibodies is by immunoadsorption in which the antibodies are specifically removed by an adsorber. For this procedure there is no need to substitute blood products. This review article describes the principles of the two different treatment methods, the advantages and disadvantages and also summarizes the current evidence for their use in rheumatological diseases.

[Hyperuricemia - more than gout : Impact on cardiovascular risk and renal insufficiency]. / Hyperurikämie - mehr als Gicht : Auswirkung auf das kardiovaskuläre Risiko und die Niereninsuffizienz.

BACKGROUND: Hyperuricemia is not only associated with gout but also with hypertension, atherosclerosis and chronic kidney disease (CKD); however, in cases of disproportionally high serum uric acid levels without symptoms of gout and slowly progressive chronic kidney failure especially in young people, a genetic cause of hyperuricemia needs to be considered. PATHOGENETIC ASSOCIATIONS: The results of experimental studies suggest that hyperuricemia can be a pathophysiologically relevant cardiovascular risk factor. In animal studies hyperuricemia leads to oxidative stress and vascular dysfunction and chronically elevated uric acid levels can result in structural changes of the vessel wall. Epidemiological data show a connection between hyperuricemia and hypertension and uric acid lowering therapy has been shown to lower arterial blood pressure. In CKD, uric acid increases in parallel with the decline in GFR and an increase in proteinuria. Several ongoing prospective clinical trials will clarify if pharmacological lowering of uric acid will translate into reduction of relevant cardiovascular and renal endpoints. THERAPY: The treatment of gout and the medicinal prophylaxis of further gout attacks depend on the comorbidities and especially CKD.

[The EHEC O104:H4 outbreak in Germany 2011 - lessons learned?!]. / Der EHEC O104:H4 Ausbruch 2011 in Deutschland - Lektion gelernt?!

The EHEC O104:H4 outbreak 2011 in Germany provided numerous insights into the recognition and control of such epidemic situations. Food-borne outbreaks and their related dynamics may lead to a critical burden of disease and an eventual capacity overload of the medical care system. Possible difficulties in the microbiological diagnostics of new or significantly altered infectious agents may result in a delayed detection of the outbreak as well as the launching of interventional measures. Besides an early notification of the local public health office by the affected institutions, in which a complete electronic procedure and additional sentinel or surveillance instruments (e. g., in emergency departments of hospitals) may be of great help, an interdisciplinary cooperation of the local public health and food safety agencies is the key to an effective outbreak control. Corresponding organizations on the state and federal level should support the investigation process by microbiological diagnostics and advanced epidemiological analysis as well as examination of the food chains. Finally, successful crisis communication relies on "speaking with one voice" (not necessarily one person). Immediate, transparent, appropriate and honest information of the general public concerning the reasons, consequences and (counter-) measures of a crisis are the best means to keep the trust of the population and to counteract the otherwise inevitable speculations.

[Thrombotic microangiopathy]. / Thrombotische Mikroangiopathien.

Thrombotic microangiopathy should be suspected every time the combination of microangiopathic hemolytic anemia without a coexisting cause, thrombocytopenia as well as renal and/or neurologic abnormalities occurs. The general term thrombotic microangiopathy includes different subtypes of the disease leading to abnormalities in multiple organ systems by endothelial injury and formation of platelet-rich thrombi in small vessels. The main types include thrombotic thrombocytopenic purpura in case of dominant neurologic abnormalities and the hemolytic uremic syndrome in case of acute kidney injury, respectively. Although these syndromes differ in their etiologies, clinical features, response to treatment, and prognosis, an early initiation of a direct therapeutic intervention frequently determines the clinical course of the patient. Irrespectively of the underlying etiology, plasma exchange is an essential component of acute therapeutic intervention while ongoing diagnostics are used to identify the definite treatment.

Renal comorbidity after solid organ and stem cell transplantation.

After transplantation of solid organs or hematopoietic stem cells, a significant acute decrease in renal function occurs in the majority of patients. Depending on the degree of kidney injury, a large number of patients develop chronic kidney disease (CKD) and some develop end-stage renal disease requiring renal replacement therapy. The incidence varies depending on the transplanted organ, but important risk factors for the development of CKD are preexisting renal disease, hepatitis C, diabetes, hypertension, age, sex, posttransplant acute kidney injury and thrombotic microangiopathy. This review article focuses on the risk factors of posttransplant chronic kidney disease after organ transplantation, considering the current literature and integrates the incidence and the associated mortality rates of acute and chronic kidney disease. Furthermore, we introduce the RECAST (REnal Comorbidity After Solid organ and hematopoietic stem cell Transplantation) registry.

[Pharmacotherapy in patients suffering from chronic kidney disease]. / Pharmakotherapie bei Patienten mit chronischer Nierenkrankheit.

The number of patients suffering from chronic kidney disease (CKD) is increasing worldwide and exceeds 15% of the entire population in industrialized countries. Half of the patients aged 70 + years suffer from CKD. The most prevalent underlying diseases leading to CKD are diabetes and hypertension. CKD per se increases the risk of cardiovascular events, cancer, and infections; hence, adequate and intensified pharmacotherapy is of utmost importance in this patient population. About 60% of all regularly used drugs are excreted by the kidney. For those, dose adjustment is of utter importance to avoid untoward effects and serious complications. The first important step for dose adjustment is the accurate estimation of renal function, i.e., glomerular filtration rate (GFR). Renal function cannot be assessed by serum creatinine alone as it only rises after a substantial (> 50%) loss of glomerular function and depends on many factors, e.g., age, gender, weight, and race. GFR can easily be estimated using formulas, e.g., the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.

[Treatment of typical hemolytic-uremic syndrome. Knowledge gained from analyses of the 2011 E. coli outbreak]. / Therapie des typischen hämolytisch-urämischen Syndroms. Erkenntnisse aus dem E.-coli-Ausbruch 2011.

Shiga toxin-associated hemolytic uremic syndrome (HUS) is an entity of thrombotic microangiopathy characterized by hemolytic anemia, thrombocytopenia, central nervous symptoms, and renal insufficiency. In May 2011, an outbreak of enterohemorrhagic Escherichia coli (EHEC; O104:H4) occurred in Northern Germany. By the end of July 2011, the outbreak was over but nearly 4000 patients had an EHEC infection, 855 cases of hemolytic-uraemic syndrome were reported to the Robert Koch Institute, and there were 35 (4.1%) deaths. Shiga toxin-induced HUS is a rare disease and no controlled clinical trials on therapeutic options are available. First analyses of this outbreak suggest that therapeutic plasma exchange, which was used in the majority of patients, had no benefit and might even be harmful. The role of eculizumab, a monoclonal antibody which inhibits the complement system, is being examined in a multicenter study: the results have not been published yet. Promising is the use of some antibiotics. This would change a paradigm that antibiotics should be avoided. Ongoing and future analyses of the epidemic should be awaited before a final recommendation regarding the different treatment strategies can be made.

Elevation of serum CXCL13 in SLE as well as in sepsis.

Recent studies have demonstrated that CXCL13 serum levels correlate significantly with systemic lupus erythematosus (SLE) disease activity. However, experimental studies show that CXCL13 production can also be induced by bacterial exposure as well as in response to inflammatory cytokines. This report asks whether CXCL13 serum levels are elevated in patients with evidence of bacterial infections and whether there is a correlation with the C-reactive protein (CRP) levels or the severity of illness in critically ill patients. CXCL13 levels were compared in 39 patients with active SLE (without concomitant infection), 40 non-SLE patients with sepsis, and 40 healthy controls by enzyme-linked immunosorbent assay (ELISA) methodology. We also tested storage conditions and freeze-thaw cycles for stability of CXCL13 in serum samples. Our studies demonstrated that the median CXCL13 serum levels were significantly elevated in patients with SLE [median 83 pg/ml (interquartile range 38-366)] or sepsis [359 pg/ml (151-459)] compared with healthy controls [32 pg/ml (27-41), p < 0.001]. The CXCL13 serum levels correlated with disease activity in SLE (CXCL13 vs. SLEDAI r = 0.65, p < 0.001), but were not associated with severity of illness score in critically ill patients (CXCL13 vs. SOFA r = -0.15, p = 0.35). However, CXCL13 serum levels were clearly associated with CRP levels in both sepsis (r = 0.45, p = 0.003) and SLE (r = 0.39, p = 0.02). In conclusion, CXCL13 is a stable serum marker for disease activity in SLE patients, but concomitant infections can also lead to increased CXCL13 levels.

Successful treatment of life-threatening pentoxifylline intoxication by high-flux hemodialysis.

High-flux hemodialysis is the method of choice for the treatment of many life threatening intoxications. Reports on intoxication with pentoxifylline are rare, and although pharmacokinetic properties of the drug suggest a potential role for hemodialysis, there are no published reports on extracorporeal treatment attempts. We report the first case of successful treatment of potentially life-threatening pentoxifylline intoxication by high-flux hemodialysis. Based on this single case, dialysis should be considered, especially in anuric patients with pentoxifylline intoxication.

[Fomepizole, ethanol or dialysis in the case of life-threatening ethylenglycol intoxication?] / Fomepizol, Ethanol oder Dialyse bei lebensbedrohlicher Ethylenglykolvergiftung?

The EXTRIP (EXtracorporeal Treatments In Poisoning) workgroup is a collaborative international effort of pharmacologists, toxicologists, critical care physicians and nephrologists reviewing all available evidence in extracorporeal procedures for the treatment of intoxications in a standardized way to distill treatment recommendations for the physician at the bedside. The second round of guidelines will include recommendations for ethylenglycol intoxication. The case reported here is of a 60-year old man with a body weight of 65 kg who ingested approximately half a bottle (500 mL) of Aral Antifreeze in a suicidal attempt and presented around 12 h later with severe metabolic acidosis (venous blood gas analysis: pH 7.13; lactate 30 mmol/l, anion gap 23.3 mmol/l). As fomepizole, the inhibitor of the alcohol dehydrogenase, was not readily available, therapy with intermittent hemodialysis was started, as well as ethanol infusion. The first available ethylenglycol concentration before prolonged intermittent hemodialysis was 1230 mg/L. The total removed amount of ethylenglycol during intermittent hemodialysis, as well as following prolonged intermittent renal replacement therapy, was quantified (102 and 65 g). Based on this case report, the new EXRIP recommendations for the role of extracorporeal treatment in the case of ethylenglycol intoxication are discussed.

Melkersson-Rosenthal syndrome in the context of sarcoidosis: a case report.

BACKGROUND: Melkersson-Rosenthal syndrome is a rare disease characterized by the triad of recurrent orofacial swelling with facial paralysis and fissured dorsal tongue. Histologically, noncaseating granulomatous inflammation occurs that confirms the diagnosis. Overlaps between granulomatous diseases such as sarcoidosis and Crohn's disease are described. Systemic corticosteroid therapy is the treatment of choice for acute attacks. CASE PRESENTATION: We here present a case of a 59-year-old White woman suffering from Melkersson-Rosenthal syndrome with a past history of sarcoidosis on therapy with leflunomide in combination with low-dose tacrolimus successfully treated with the anti-leprosy drug clofazimine after failure of systemic steroid therapy. CONCLUSIONS: We propose clofazimine as an alternative treatment in steroid-refractory cases.

[Nephrogenic systemic fibrosis: a rare disease with grave consequences]. / Nephrogene systemische Fibrose: Eine seltene Erkrankung mit schwerwiegenden Folgen.

Nephrogenic systemic fibrosis (NSF) is a progressive, potentially fatal systemic multiorgan fibrosing disease related to exposure of patients with advanced renal failure to the gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging. Because of this relationship between nephrogenic systemic fibrosis and gadolinium-based contrast agents, the U.S. Food and Drug Administration currently warns against using gadolinium-based contrast agents in patients with a glomerular filtration rate less than 30 ml per minute per 1.73 m(2), or any acute kidney injury related to the hepatorenal syndrome or perioperative liver transplantation. Linear non-ionic GBCAs that are more prone to release free gadolinium are the more likely to cause NSF. The mechanism for NSF is not fully understood, yet risk factors have been described. As there is no established therapy for NSF the prevention of exposure to gadolinium is crucial in high risk patients.

A bitter pill to swallow.

Foreign body aspiration can be a life-threatening emergency requiring immediate intervention. However, unlike in children, clinical presentation of foreign bodies in adults often varies with regard to symptoms and signs and occurs without asphyxia. We here describe the case of a 65-year-old man on maintenance hemodialysis who developed dyspnea and left chest aspiration pneumonia after swallowing one tablet of the phosphate binder sevelamer. This case illustrates that elderly patients with swallowing complaints should be taken serious when they complain about their subsequent frustration of ingestion of their pills.

Fish, flesh and a good red herring: a case of ascending upper limb infection in a renal transplant patient.

While newly developed potent immunosuppressive agents have dramatically reduced the incidence of rejection of transplanted organs, they have increased the patients' susceptibility to opportunistic infections and cancer. Here we report a rare skin infection caused by atypical mycobacterium marinum in a 50-year-old female renal transplant recipient. The patient presented with localized skin lesion on the dorsum of her hand, which was misdiagnosed as gout. Only after the lesions spread in a sporotrichoid pattern, a cutaneous infection with atypical mycobacteria was suspected. The diagnosis was based on histopathological analysis as well as mycobacterial culture, both showing infection with atypical mycobacterium. Three months of antimycobacterial treatment led to a marked regression of the lesions. Sporotrichoid lesions in renal transplant patients are rare and a diagnostic challenge for the physician. A thorough history and a low threshold for skin biopsies could prevent painful and unnecessary surgical interventions.

[Hot rods in the ICU : What is the antibiotic mileage of your renal replacement therapy?] / Boliden auf der Intensivstation : Wie viel Antibiotika verbraucht Ihre Nierenersatztherapie pro Tag?

We would neither be disappointed nor upset if the gas mileage on the sticker of a car didn't match our personal, real-life fuel consumption. Depending on our daily route to work, our style of accelerating and the number of passengers in our carpool, the gas mileage will vary. As soon as the falcon wing door of our car is closed and entrance to the ICU is granted, we tend to forget all of this, even though another hot rod is waiting there for us. Renal replacement therapy is like a car; it fulfills goals, such as the removal of uremic toxins and accumulated fluids, but it also "consumes" (removes) antibiotics. Unlike catecholamines, where we have the mean arterial pressure on our ICU dashboard, we do not have a gauge to measure antibiotic "consumption", i.e. elimination by renal replacement therapy. This manuscript describes the principles and basic knowledge to improve dosing of antibiotics in critically ill patients undergoing renal replacement therapy. As in modern cars, we briefly touch on hybrid therapies combining renal replacement therapy with extracorporeal lung support or adsorbent technologies that remove cytokines or bacteria. Further, the importance of considering body size and body composition is addressed, especially for choosing the right initial dose of antibiotics. Lastly we point out the dire need to increase the availability of timely and affordable therapeutic drug monitoring on the most commonly used antiinfectives, ideally using point-of-care devices at the bedside.

International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

[Metabolic management and nutrition in critically ill patients with renal dysfunction : Recommendations from the renal section of the DGIIN, ÖGIAIN, and DIVI]. / Metabolische Führung und Ernährung von Intensivpatienten mit renaler Dysfunktion : Empfehlungen der Sektionen Niere der DGIIN, ÖGIAIN und DIVI.

BACKGROUND: Intensive care patients with renal failure or insufficiency comprise a heterogeneous group of subjects with widely differing metabolic patterns and nutritional requirements. They include subjects with various stages of acute kidney injury (AKI), acute-on-chronic renal failure (A-CKD), without/with renal replacement therapy (RRT), chronic kidney disease (CKD), and subjects on regular hemodialysis or peritoneal dialysis therapy (HD/PD). GOALS: Development of recommendations by the renal section of DGIIN (Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), ÖGIAIN (Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) for the metabolic management and the planning, indication, implementation, and monitoring of nutrition therapy in this heterogeneous group of patients. MATERIALS AND METHODS: The recommendations are based on recent evidence and current recommendations of DGEM (Deutsche Gesellschaft für Ernährungsmedizin), ASPEN (American Society for Parenteral and Enteral Nutrition) and ESPEN (European Society for Clinical Nutrition and Metabolism) and also the KDGIO (Kidney Disease: Improving Global Outcomes) clinical practice guidelines for AKI and the expert knowledge and clinical experience of the authors. RESULTS: Nutrition support in these patient groups is not fundamentally different from that in other disease states but must consider the multiple variations in metabolism and nutrient requirements. Nutrition therapy must be adapted to the stage of disease and especially, in those patients on RRT. Nutritional needs can differ widely between patients but also in the same patient during the course of the disease. CONCLUSIONS: Thus, the patient with renal failure requires an individualized approach in nutrition support and because of the altered metabolism of many nutrients and intolerances for electrolytes and fluids, the nutrition support in patients with renal insufficiency requires close clinical and laboratory monitoring.