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Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD., Competing Interests: I.D. has received research grants from Baxter, Medtronic and Sanofi and honoraria for advisory boards and speaker meetings from AstraZeneca, Bayer, GSK, Sanofi and Vifor Pharma. M.F. has received consultancy fees from AstraZeneca and GSK. H.F. has received consultancy and speaker fees from AstraZeneca, BMS, Sanofi, GSK and Vifor Pharma. L.G.’s university department (DIMEPRE-J) received research grants from Abionyx and Sanofi; he has received consultancy and speaker fees from AstraZeneca, Baxter, Chinook, GSK, Medtronic, Mundipharma, Novartis, Pharmadoc, F. Hoffmann-La Roche Ltd, Sandoz, Sanofi, Travere, Vifor Pharma, Astellas Pharma, Estor, Fresenius Kabi and Werfen. N.H. is an employee of GSK. R.M. has been a member of advisory boards for Amgen, Astellas Pharma and GSK; has received consultancy fees from Bayer and GSK and has been an invited speaker at meetings supported by Amgen, Astellas Pharma, AstraZeneca and Vifor Pharma. A.P. has received consultancy fees from AstraZeneca and GSK. J.P. has received consultancy and speaker fees from Astellas Pharma, GSK and Vifor Pharma. C.R. has received consultancy and speaker fees from Akebia, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, GSK, Otsuka and Vifor Pharma. J.E.S.A. has received consultancy and speaker fees from Astellas Pharma, Baxter, GSK and Vifor Pharma. P.U.T. has received honoraria for advisory boards and speaker meetings from Amgen, Astellas Pharma, AstraZeneca, Baxter, GSK, Théradial and Vifor Pharma. R.C.V. is an advisor to AstraZeneca, Baxter, Fresenius Kabi, Fresenius Medical Care, GSK, Kibow Biotech, Nextkidney, Nipro and Novartis. C.W. has received consultancy fees from Amgen, Amicus, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Vifor Pharma, Chiesi, Chugai, Fresenius Medical Care, GSK, Idorsia, Eli Lilly, MSD, Novartis and Novo Nordisk and grants and consultancy fees from Boehringer Ingelheim and Sanofi. C.I.B. and D.G.Z. have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: Large international differences exist in kidney transplantation (KT) rates. We aimed to investigate which factors may explain the total, deceased donor and living donor KT rates over the last decade., Methods: KT experts from 39 European countries completed the Kidney Transplantation Rate Survey on measures and barriers and their potential effect on the KT rate in their country. In the analyses, countries were divided into low, middle and high KT rate countries based on the KT rate at the start of study period in 2010., Results: Experts from low KT rate countries reported more frequently that they had taken measures regarding staff, equipment and facilities to increase the total KT rate compared with middle and high KT rate countries. For donor type-specific KT, the largest international differences in measures taken were reported for deceased donor KT, with middle and high KT rate countries taking more measures, such as the use of expanded criteria donor kidneys, the presence of transplantation coordinators and (inter)national exchange of donor kidneys. Once a measure was taken, experts' opinion on its success was similar across the low, middle and high KT rate countries. Experts from low KT rate countries more often reported potential barriers, such as patients' lack of knowledge and distrust in the healthcare system., Conclusions: Particularly in low KT rate countries, the KT rate might be stimulated by optimizing staff, equipment and facilities. In addition, all countries may benefit from measures specific to deceased and living donors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Access to various kidney replacement therapy (KRT) modalities for patients with end-stage kidney disease differs substantially within Europe., Methods: European adults on KRT filled out an online or paper-based survey about factors influencing and experiences with modality choice (e.g. information provision, decision-making and reasons for choice) between November 2017 and January 2019. We compared countries with low, middle and high gross domestic product (GDP)., Results: In total, 7820 patients [mean age 59 years, 56% male, 63% on centre haemodialysis (CHD)] from 38 countries participated. Twenty-five percent had received no information on the different modalities, and only 23% received information >12 months before KRT initiation. Patients were not informed about home haemodialysis (HHD) (42%) and comprehensive conservative management (33%). Besides nephrologists, nurses more frequently provided information in high-GDP countries, whereas physicians other than nephrologists did so in low-GDP countries. Patients from low-GDP countries reported later information provision, less information about other modalities than CHD and lower satisfaction with information. The majority of modality decisions were made involving both patient and nephrologist. Patients reported subjective (e.g. quality of life and fears) and objective reasons (e.g. costs and availability of treatments) for modality choice. Patients had good experiences with all modalities, but experiences were better for HHD and kidney transplantation and in middle- and high-GDP countries., Conclusion: Our results suggest European differences in patient-reported factors influencing KRT modality choice, possibly caused by disparities in availability of KRT modalities, different healthcare systems and varying patient preferences. Availability of home dialysis and kidney transplantation should be optimized., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Access to forms of dialysis, kidney transplantation (Tx) and comprehensive conservative management (CCM) for patients with end-stage kidney disease (ESKD) varies across European countries. Attitudes of nephrologists, information provision and decision-making may influence this access and nephrologists may experience several barriers when providing treatments for ESKD., Methods: We surveyed European nephrologists and kidney transplant surgeons treating adults with ESKD about factors influencing modality choice. Descriptive statistics were used to compare the opinions of professionals from European countries with low-, middle- and high-gross domestic product purchasing power parity (GDP PPP)., Results: In total, 681 professionals from 33 European countries participated. Respondents from all GDP categories indicated that ∼10% of patients received no information before the start of renal replacement therapy (RRT) (P = 0.106). Early information provision and more involvement of patients in decision-making were more frequently reported in middle- and high-GDP countries (P < 0.05). Professionals' attitudes towards several treatments became more positive with increasing GDP (P < 0.05). Uptake of in-centre haemodialysis was sufficient to 73% of respondents, but many wanted increased uptake of home dialysis, Tx and CCM. Respondents experienced different barriers according to availability of specific treatments in their centre. The occurrence of barriers (financial, staff shortage, lack of space/supplies and patient related) decreased with increasing GDP (P < 0.05)., Conclusions: Differences in factors influencing modality choice when providing RRT or CCM to adults with ESKD were found among low-, middle- and high-GDP countries in Europe. Therefore a unique pan-European policy to improve access to treatments may be inefficient. Different policies for clusters of countries could be more useful., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

The aims of this study were to determine the frequency of dialysis and kidney transplantation and to estimate the regularity of comprehensive conservative management (CCM) for patients with kidney failure in Europe. This study uses data from the ERA-EDTA Registry. Additionally, our study included supplemental data from Armenia, Germany, Hungary, Ireland, Kosovo, Luxembourg, Malta, Moldova, Montenegro, Slovenia and additional data from Israel, Italy, Slovakia using other information sources. Through an online survey, responding nephrologists estimated the frequency of CCM (i.e. planned holistic care instead of kidney replacement therapy) in 33 countries. In 2016, the overall incidence of replacement therapy for kidney failure was 132 per million population (pmp), varying from 29 (Ukraine) to 251 pmp (Greece). On 31 December 2016, the overall prevalence of kidney replacement therapy was 985 pmp, ranging from 188 (Ukraine) to 1906 pmp (Portugal). The prevalence of peritoneal dialysis (114 pmp) and home hemodialysis (28 pmp) was highest in Cyprus and Denmark respectively. The kidney transplantation rate was nearly zero in some countries and highest in Spain (64 pmp). In 28 countries with five or more responding nephrologists, the median percentage of candidates for kidney replacement therapy who were offered CCM in 2018 varied between none (Slovakia and Slovenia) and 20% (Finland) whereas the median prevalence of CCM varied between none (Slovenia) and 15% (Hungary). Thus, the substantial differences across Europe in the frequency of kidney replacement therapy and CCM indicate the need for improvement in access to various treatment options for patients with kidney failure., (Copyright © 2021 International Society of Nephrology. All rights reserved.)

Populations in the high-income countries of Western Europe are aging due to increased life expectancy. As the prevalence of diabetes and obesity has increased, so has the burden of kidney failure. To determine the global capacity for kidney replacement therapy and conservative kidney management, the International Society of Nephrology conducted multinational, cross-sectional surveys and published the findings in the International Society of Nephrology Global Kidney Health Atlas. In the second iteration of the International Society of Nephrology Global Kidney Health Atlas, we aimed to describe the availability, accessibility, quality, and affordability of kidney failure care in Western Europe. Among the 29 countries in Western Europe, 21 (72.4%) responded, representing 99% of the region's population. The burden of kidney failure prevalence varied widely, ranging from 760 per million population (pmp) in Iceland to 1612 pmp in Portugal. Coverage of kidney replacement therapy from public funding was nearly universal, with the exceptions of Germany and Liechtenstein where part of the costs was covered by mandatory insurance. Fourteen (67%) of 21 countries charged no fees at the point of care delivery, but in 5 countries (24%), patients do pay some out-of-pocket costs. Long-term dialysis services (both hemodialysis and peritoneal dialysis) were available in all countries in the region, and kidney transplantation services were available in 19 (90%) countries. The incidence of kidney transplantation varied widely between countries from 12 pmp in Luxembourg to 70.45 pmp in Spain. Conservative kidney care was available in 18 (90%) of 21 countries. The median number of nephrologists was 22.9 pmp (range: 9.47-55.75 pmp). These data highlight the uniform capacity of Western Europe to provide kidney failure care, but also the scope for improvement in disease prevention and management, as exemplified by the variability in disease burden and transplantation rates., (© 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rationale & Objective: Previous studies of inflammation and anemia management in hemodialysis (HD) patients may be biased due to patient differences. We used a self-matched longitudinal design to test whether new inflammation, defined as an acute increase in C-reactive protein (CRP) level, reduces hemoglobin response to erythropoiesis-stimulating agent (ESA) treatment., Study Design: Self-matched longitudinal design., Setting & Participants: 3,568 new inflammation events, defined as CRP level > 10 mg/L following a 3-month period with CRP level ≤ 5 mg/L, were identified from 12,389 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018) in 10 countries in which CRP is routinely measured., Predictor: "After" (vs "before") observing a high CRP level., Outcomes: Within-patient changes in hemoglobin level, ESA dose, and ESA hyporesponsiveness (hemoglobin < 10 g/dL and ESA dose > 6,000 [Japan] or >8,000 [Europe] U/wk)., Analytical Approach: Linear mixed models and modified Poisson regression., Results: Comparing before with after periods, mean hemoglobin level decreased from 11.2 to 10.9 g/dL (adjusted mean change, -0.26 g/dL), while mean ESA dose increased from 6,320 to 6,960 U/wk (adjusted relative change, 8.4%). The prevalence of ESA hyporesponsiveness increased from 7.6% to 12.3%. Both the unadjusted and adjusted prevalence ratios of ESA hyporesponsiveness were 1.68 (95% CI, 1.48-1.91). These associations were consistent in sensitivity analyses varying CRP thresholds and were stronger when the CRP level increase was sustained over the 3-month after period., Limitations: Residual confounding by unmeasured time-varying risk factors for ESA hyporesponsiveness., Conclusions: In the 3 months after HD patients experienced an increase in CRP levels, hemoglobin levels declined quickly, ESA doses increased, and the prevalence of ESA hyporesponsiveness increased appreciably. Routine CRP measurement could identify inflammation as a cause of worsened anemia. In turn, these findings speak to a potentially important role for anemia therapies that are less susceptible to the effects of inflammation., (© 2020 The Authors.)

Background: Cross-sectional health-related quality of life (HR-QOL) measures are associated with mortality in hemodialysis (HD) patients. The impact of changes in HR-QOL on outcomes remains unclear. We describe the association of prior changes in HR-QOL with subsequent mortality among HD patients., Methods: A total of 13 784 patients in the Dialysis Outcomes and Practice Patterns Study had more than one measurement of HR-QOL. The impact of changes between two measurements of the physical (PCS) and mental (MCS) component summary scores of the SF-12 on mortality was estimated with Cox regression., Results: Mean age was 62 years (standard deviation: 14 years); 59% were male and 32% diabetic. Median time between HR-QOL measurements was 12 months [interquartile range (IQR): 11, 14]. Median initial PCS and MCS scores were 37.5 (IQR: 29.4, 46.2) and 46.4 (IQR: 37.2, 54.9); median changes in PCS and MCS scores were -0.2 (IQR: -5.5, 4.7) and -0.1 (IQR: -6.8, 5.9), respectively. The adjusted hazard ratio (HR) for a 5-point decline in HR-QOL score was 1.09 [95% confidence interval (CI): 1.06-1.12] for PCS and 1.05 (95% CI: 1.03-1.08) for MCS. Adjusting for the second QOL score, the change was not associated with mortality: HR = 1.01 (95% CI: 0.98-1.05) for delta PCS and 1.01 (95% CI: 0.98-1.03) for delta MCS. Categorizing the first and second scores as predictors, only the second PCS or MCS score was associated with mortality., Conclusions: In our study, only the most recent HR-QOL score was associated with mortality. Hence, the predictive power of a measurement of HR-QOL is not affected by changes in HR-QOL prior to that measurement; more frequent HR-QOL measurements are needed to improve the prediction of outcomes in HD. Further studies are needed to determine the optimal frequency and appropriate instrument to be used for serial measurements., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

In this article, we review approaches for decreasing uremic solute concentrations in chronic kidney disease and in particular, in end-stage renal disease (ESRD). The rationale to do so is the straightforward relation between concentration and biological (toxic) effect for most toxins. The first section is devoted to extracorporeal strategies (kidney replacement therapy). In the context of high-flux hemodialysis and hemodiafiltration, we discuss increasing dialyzer blood and dialysate flows, frequent and/or extended dialysis, adsorption, bioartificial kidney, and changing physical conditions within the dialyzer (especially for protein-bound toxins). The next section focuses on the intestinal generation of uremic toxins, which in return is stimulated by uremic conditions. Therapeutic options are probiotics, prebiotics, synbiotics, and intestinal sorbents. Current data are conflicting, and these issues need further study before useful therapeutic concepts are developed. The following section is devoted to preservation of (residual) kidney function. Although many therapeutic options may overlap with therapies provided before ESRD, we focus on specific aspects of ESRD treatment, such as the risks of too-strict blood pressure and glycemic regulation and hemodynamic changes during dialysis. Finally, some recommendations are given on how research might be organized with regard to uremic toxins and their effects, removal, and impact on outcomes of uremic patients., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Physical activity has been associated with better health status in diverse populations, but the association in patients on maintenance hemodialysis is less established. Patient-reported physical activities and associations with mortality, health-related quality of life, and depression symptoms in patients on maintenance hemodialysis in 12 countries were examined., Design, Setting, Participants, & Measurements: In total, 5763 patients enrolled in phase 4 of the Dialysis Outcomes and Practice Patterns Study (2009-2011) were classified into five aerobic physical activity categories (never/rarely active to very active) and by muscle strength/flexibility activity using the Rapid Assessment of Physical Activity questionnaire. The Kidney Disease Quality of Life scale was used for health-related quality of life. The Center for Epidemiologic Studies Depression scale was used for depression symptoms. Linear regression was used for associations of physical activity with health-related quality of life and depression symptoms scores. Cox regression was used for association of physical activity with mortality., Results: The median (interquartile range) of follow-up was 1.6 (0.9-2.5) years; 29% of patients were classified as never/rarely active, 20% of patients were classified as very active, and 20.5% of patients reported strength/flexibility activities. Percentages of very active patients were greater in clinics offering exercise programs. Aerobic activity, but not strength/flexibility activity, was associated positively with health-related quality of life and inversely with depression symptoms and mortality (adjusted hazard ratio of death for very active versus never/rarely active, 0.60; 95% confidence interval, 0.47 to 0.77). Similar associations with aerobic activity were observed in strata of age, sex, time on dialysis, and diabetes status., Conclusions: The findings are consistent with the health benefits of aerobic physical activity for patients on maintenance hemodialysis. Greater physical activity was observed in facilities providing exercise programs, suggesting a possible opportunity for improving patient outcomes., (Copyright © 2014 by the American Society of Nephrology.)

Disasters result in a substantial number of renal challenges, either by the creation of crush injury in victims trapped in collapsed buildings or by the destruction of existing dialysis facilities, leaving chronic dialysis patients without access to their dialysis units, medications, or medical care. Over the past two decades, lessons have been learned from the response to a number of major natural disasters that have impacted significantly on crush-related acute kidney injury and chronic dialysis patients. In this paper we review the pathophysiology and treatment of the crush syndrome, as summarized in recent clinical recommendations for the management of crush syndrome. The importance of early fluid resuscitation in preventing acute kidney injury is stressed, logistic difficulties in disaster conditions are described, and the need for an implementation of a renal disaster relief preparedness program is underlined. The role of the Renal Disaster Relief Task Force in providing emergency disaster relief and the logistical support required is outlined. In addition, the importance of detailed education of chronic dialysis patients and renal unit staff in the advance planning for such disasters and the impact of displacement by disasters of chronic dialysis patients are discussed.

Background: Accelerated vascular calcification and increased risk of calciphylaxis can be a reason to restrict the use of vitamin K antagonists in dialysis patients. We describe the use of fondaparinux, a prototype indirect factor Xa inhibitor, as an alternative anticoagulant to coumarin derivatives in dialysis patients., Methods: In this case series, we included six chronic haemodialysis patients treated with vitamin K antagonists. Low-molecular-weight heparin given as anticoagulant during dialysis was replaced by fondaparinux. Anti-Xa activity was regularly measured pre- and postdialysis to adapt the dose of fondaparinux. Adequate continuous anticoagulation and circuit patency were registered by evaluating clotting in the bubble trap and dialyser membrane at the end of dialysis., Results: Anticoagulation with fondaparinux at a starting dose of 2.5 mg resulted in an effective anticoagulation in the majority of dialysis sessions. Although median predialysis anti-Xa levels were significantly lower [0.36 IU/mL (0.30-0.42 IU/mL) (P < 0.0001)] than postdialysis levels [0.75 IU/mL (0.65-0.80 IU/mL)], predialysis anti-Xa levels were sufficient to limit the risk of thromboembolism. After an initial period of gradually increasing anti-Xa levels due to accumulation of fondaparinux, stable levels were achieved. Haemodialysis without clotting problems was possible in 96% of the sessions (clotting score ≤1), whereas two episodes (2/459 dialysis sessions) of major clotting were observed, defined as clotting of the extracorporeal circuit necessitating premature termination of the procedure., Conclusions: We demonstrated that fondaparinux is a valuable anticoagulant for patients dialysed with low-flux membranes in need of continuous anticoagulation.

We discuss the performance of novel biomarkers in acute kidney injury (AKI). Comparison of the areas under the receiver operating characteristic curves of several biomarkers with some clinical and/or routine biochemical outcome parameters reveals that none of the biomarkers has demonstrated a clear additional value beyond the traditional approach in clinical decision making in patients with AKI. Unscrutinized use of these biomarkers may distract from adequate clinical evaluation and carries the risk of worse instead of better patient outcome.

Besides victims with acute kidney injury, disasters may also affect the destiny of chronic dialysis patients. This Commentary discusses the article by Kutner et al. describing the outcome of chronic dialysis patients who were victims of Hurricane Katrina. The importance of advance disaster plans, including instructions to chronic dialysis patients, is emphasized. In addition, it is expected that specific recommendations, which are currently being prepared, will offer ad hoc advice to rescuers.

Objectives: Critically ill patients with infection are at increased risk for developing acute renal failure (ARF), and ARF is associated with an increased risk for infection. Both conditions are associated with prolonged length of stay (LOS) and worse outcome; however, little data exist on the epidemiology of infection in this specific cohort. Therefore, we investigated the occurrence of infection in a cohort of critically ill patients with ARF treated with renal replacement therapy (RRT). In addition, we assessed whether this infection worsened outcome., Design: Retrospective cohort study., Setting: General intensive care unit (ICU) in an academic tertiary care center comprising a 22-bed surgical ICU, eight-bed cardiac surgery ICU, 14-bed medical ICU, and six-bed burn center., Patients: Six hundred forty-seven consecutive critically ill patients with ARF treated with RRT, admitted between 2000 and 2004., Interventions: None., Measurements and Main Results: total of 519 (80.2%), 193 (29.8%), 66 (10.2%), and ten (1.5%) patients developed one, two, three, and four episodes of infection, respectively. Of 788 episodes of infection observed, 364 (46.2%) occurred before, 318 (40.3%) during, and 106 (13.4%) after discontinuation of RRT. Pneumonia (54.3%) was most frequent, followed by intra-abdominal (11.9%) and urinary tract infections (9.7%). Infections were caused by Gram-negative organisms in 33.7%, Gram-positive organisms in 21.6%, and yeasts in 9.8%. Patients with infection had higher mortality (p = 0.04) and longer ICU and hospital LOS. They needed more vasoactive therapy and spent more time on mechanical ventilation and RRT (all p < 0.001) than patients without infection. After adjustment for potential confounders, Acute Physiology and Chronic Health Evaluation II score, age, mechanical ventilation, and vasoactive therapy were associated with worse outcome, but infection was not., Conclusions: Infection occurred in four fifths of critically ill patients with ARF treated with RRT and was in an unadjusted analysis associated with longer LOS and higher mortality. After correction for other covariates, infection was no longer associated with in-hospital mortality.

Coronary artery disease (CAD) is a major cause of mortality and morbidity. Noninvasive proteome analysis could guide clinical evaluation and early/preventive treatment. Under routine clinical conditions, urine of 67 patients presenting with symptoms suspicious for CAD were analyzed by capillary electrophoresis directly coupled with mass spectrometry (CE-MS). All patients were subjected to coronary angiography and either assigned to a CAD or non-CAD group. A training set of 29 patients was used to establish CAD and non-CAD-associated proteome patterns of plasma as well as urine. Significant discriminatory power was achieved in urine but not in plasma. Therefore, urine proteomic analysis of further 38 patients was performed in a blinded study. A combination of 17 urinary polypeptides allowed separation of both groups in the test set with a sensitivity of 81%, a specificity of 92%, and an accuracy of 84%. Sequencing of urinary marker peptides identified fragments of collagen alpha1 (I and III), which we furthermore demonstrated to be expressed in atherosclerotic plaques of human aorta. In conclusion, specific CE-MS polypeptide patterns in urine were associated with significant CAD in patients with angina-typical symptoms. These promising findings need to be further evaluated in regard to reliability of a urine-based screening method with the potential of improving the diagnostic approaches for CAD.

Introduction: Antimicrobial resistance negatively impacts on prognosis. Intensive care unit (ICU) patients, and particularly those with acute kidney injury (AKI), are at high risk for developing nosocomial bloodstream infections (BSI) due to multi-drug-resistant strains. Economic implications in terms of costs and length of stay (LOS) attributable to antimicrobial resistance are underevaluated. This study aimed to assess whether microbial susceptibility patterns affect costs and LOS in a well-defined cohort of ICU patients with AKI undergoing renal replacement therapy (RRT) who developed nosocomial BSI., Methods: Historical study (1995-2004) enrolling all adult RRT-dependent ICU patients with AKI and nosocomial BSI. Costs were considered as invoiced in the Belgian reimbursement system, and LOS was used as a surrogate marker for hospital resource allocation., Results: Of the 1330 patients with AKI undergoing RRT, 92 had microbiologic evidence of nosocomial BSI (57/92, 62% due to a multi-drug-resistant microorganism). Main patient characteristics were equal in both groups. As compared to patients with antimicro-4 bial-susceptible BSI, patients with antimicrobial-resistant BSI were more likely to acquire Gram-positive infection (72.6% vs 25.5%, P<0.001). No differences were found neither in LOS (ICU before BSI, ICU, hospital before BSI, hospital, hospital after BSI, and time on RRT; all P>0.05) or hospital costs (all P>0.05) when comparing patients with antimicrobial-resistant vs antimicrobial-susceptible BSI. However, although not statistically significant, patients with BSI caused by resistant Gram-negative-, Candida-, or anaerobic bacteria incurred substantial higher costs than those without., Conclusion: In a cohort of ICU patients with AKI and nosocomial BSI undergoing RRT, patients with antimicrobial-resistant vs antimicrobial-susceptible Gram-positive BSI did not have longer hospital stays, or higher hospital costs. Patients with resistant "other" (i.e. Gram-negative, Candida, or anaerobic) BSI were found to have a distinct trend towards increased resources use as compared to patients with susceptible "other" BSI, respectively.

Kidney failure leads to the uremic syndrome that is the clinical expression of the malfunction of vital organs due to the accumulation of uremic toxins, which are normally cleared by the kidneys. Progressively more uremic retention solutes have been identified and their potential toxicity has been characterized. Polypeptides constitute a heterogeneous group of uremic molecules. Therefore, proteome analysis represents a new and promising analytical approach to identify new uremic toxins. Proteomic technologies cover applicability to a broad molecular mass range. For polypeptides >10 kDa classical proteomic techniques, such as two-dimensional gel electrophoresis followed by mass spectrometry, are able to identify uremic polypeptides. In the mass range from approximately 1 to 10 kDa, capillary electrophoresis coupled to mass spectrometry (CE-MS) emerged as a fast possibility to analyze of up to 1,400 compounds in a single step. This chapter will provide an overview about proteomic technologies as efficient tools for the detection of uremic toxins, emphasizing the features of CE-MS. Subsequently, examples of the application of proteomic techniques to define novel biomarkers for renal diseases and uremic toxins will be discussed.

Background: Arterial stiffness predicts cardiovascular disease (CVD) events and has been well documented in haemodialysis patients. Information in renal transplant recipients (RTR), however, remains limited despite their higher CVD risk compared to the general population. We aimed to assess arterial stiffening and wave reflections in RTR and healthy controls and to evaluate which factors could explain potential differences., Methods: Carotid augmentation index (AI) and carotid-femoral pulse wave velocity (PWV) were measured in 200 RTR and 44 controls using applanation tonometry. The impact of traditional and non-traditional CVD risk factors was assessed using linear regression analysis. Glomerular filtration rate (GFR) was measured by (51)Cr-EDTA (RTR) and estimated using the abbreviated Modification of Diet in Renal Disease formula (RTR and controls)., Results: After correction for age, blood pressure and anthropometry, AI and PWV remained 7.4 +/- 3.6% (P = 0.04) and 0.7 +/- 0.3 m/s (P = 0.01) higher in RTR than controls, corresponding to a difference in vascular age of >10 years. In multivariate analysis, additional independent factors related to AI and PWV were GFR (-1.8% and -0.19 m/s per 10 ml/min) and C-reactive protein (3.2% and 0.21 m/s per logarithm increase)., Conclusions: Increased arterial stiffness and wave reflections in RTR are attributable to incomplete restoration of GFR and the presence of subclinical inflammation.

Studies have produced conflicting findings on outcomes for patients with antimicrobial-resistant infection. This study evaluated whether infection with an antimicrobial-resistant organism affects outcome in critically ill patients with acute kidney injury treated with renal replacement therapy and whose clinical course is complicated with a nosocomial bloodstream infection. We found that infection with an antimicrobial-resistant organism did not adversely affect clinical outcome in this specific cohort, which already has a high mortality rate.

The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal conditions are excreted by healthy kidneys. During recent years major steps have been taken in the area of identification and characterization of uremic retention solutes and in the knowledge of their pathophysiological importance; however, our knowledge remains far from complete. In the present paper the general classification based on their molecular weight and on their protein-binding characteristics, with reflections on their removal, will be discussed. In addition, current knowledge about the main uremic retention products and their clinical and biological effects will be reviewed in detail.

Background: It has been suggested that iron increases oxidative stress and that an excess of iron contributes to cardiovascular disease and infections in haemodialysis patients. In the present study, the effects of parenterally administered iron on leucocyte surface molecule expression and the production of reactive oxygen species (ROS) were evaluated., Methods: Ten chronic haemodialysis (HD) patients without iron overload were studied. To each patient, four different regimens were applied: placebo; iron sucrose, either 30 or 100 mg, administered via the outflow dialyser line; and 100 mg of iron sucrose infused via the inflow dialyser line. Blood was sampled at different time points: before, during and after infusion and immediately before the next dialysis session. Levels of CD11b and CD45 expression on granulocytes and of CD11b, CD14 and CD36 on monocytes were determined using flow cytometric analysis. The generation of ROS was quantified using chemiluminescence with and without ex vivo stimulation by phorbol myristate acetate (PMA)., Results: No significant differences among the four different treatment regimes were found, neither in chemilumescence activity nor in the expression of CD11b and CD45 on granulocytes, and of CD11b, CD14 and CD36 on monocytes., Conclusions: Our results suggest that parenteral infusion of iron sucrose during haemodialysis in patients who have no signs of iron overload has no significant effect on the expression of leucocyte surface molecules and does not increase production of ROS.

Background: Sodium bicarbonate is despite its side effects, considered the standard alkali therapy in metabolic acidosis. THAM is an alternative alkalizing agent; however, there are limited data on the use of THAM in metabolic acidosis. The aim of this study was to compare the efficacy and adverse effects of a single dose of sodium bicarbonate and THAM in intensive care unit (ICU) patients with mild metabolic acidosis., Methods: 18 adult ICU patients with mild metabolic acidosis (serum bicarbonate < 20 mmol/L) were randomized to a single dose of either sodium bicarbonate or THAM, administered over a 1-hour period, and titrated to buffer the excess of acid load., Results: Sodium bicarbonate and THAM had equivalent alkalinizing effect during the infusion period. This was still present 4 hours after start of infusion of sodium bicarbonate, and until 3 hours after start of infusion of THAM. Serum potassium levels decreased after sodium bicarbonate infusion, and remained unchanged after THAM. After sodium bicarbonate, sodium increased, and after THAM, serum sodium decreased., Conclusions: Sodium bicarbonate and THAM had a similar alkalinizing effect in patients with mild metabolic acidosis; however, the effect of sodium bicarbonate was longer lasting. Sodium bicarbonate did decrease serum potassium, and THAM did not; THAM is therefore not recommended in patient with hyperkalemia. As sodium bicarbonate leads to an increase of serum sodium and THAM to a decrease, THAM may be the alkalinizing agent of choice in patients with hypernatremia. Similarly, because sodium bicarbonate increases PaCO2 and THAM may even decrease PaCO2, sodium bicarbonate is contraindicated and THAM preferred in patients with mixed acidosis with high PaCO2 levels.

Background: Detection of renal dysfunction is important in critically ill patients, and in daily practice, serum creatinine is used most often. Other tools allowing the evaluation of renal function are the Cockcroft-Gault and MDRD (Modification of Diet in Renal Disease) equations. These parameters may, however, not be optimal for critically ill patients. The present study evaluated the value of a single serum creatinine measurement, within normal limits, and three commonly used prediction equations for assessment of glomerular function (Cockcroft-Gault, MDRD and the simplified MDRD formula), compared with creatinine clearance (Ccr) measured on a 1 h urine collection in an intensive care unit (ICU) population., Methods: This was a prospective observational study. A total of 28 adult patients with a serum creatinine <1.5 mg/dl, within the first week of ICU admission, were included in the study. Renal function was assessed with serum creatinine, timed 1 h urinary Ccr, and the Cockcroft-Gault, MDRD and simplified MDRD equations., Results: Serum creatinine was in the normal range in all patients. Despite this, measured urinary Ccr was <80 ml/min/1.73 m2 in 13 patients (46.4%), and <60 ml/min/1.73 m2 in seven patients (25%). Urinary creatinine levels were low, especially in patients with low Ccr, suggesting a depressed production of creatinine caused by pronounced muscle loss. Regression analysis and Bland-Altman plots revealed that neither the Cockcroft-Gault formula nor the MDRD equations were specific enough for assessment of renal function., Conclusions: In recently admitted critically ill patients with normal serum creatinine, serum creatinine had a low sensitivity for detection of renal dysfunction. Furthermore, the Cockcroft-Gault and MDRD equations were not adequate in assessing renal function.

Background: Uraemic toxicity results in the dysfunction of many organ systems, provoking an increase in morbidity and mortality. To date, only approximately 90 uraemic retention solutes have been described. To examine unknown uraemic substances thoroughly, the identification of as many compounds as possible in the ultrafiltrate and/or plasma of patients would lead to a less biased definition of the uraemic retention process compared with what is proposed today., Methods: We describe the application of a novel proteomic tool for the identification of a large number of molecules present in ultrafiltrate from uraemic and normal plasma obtained with high- or low-flux membranes. Separation by capillary electrophoresis was coupled on-line to a mass spectrometer, yielding identification of polypeptides based on their molecular weight., Results: Between 500 and >1000 polypeptides with a molecular weight ranging from 800 to 10,000 Da could be detected in individual samples, and were identified via their mass and their particular migration time in capillary electrophoresis. In ultrafiltrate from uraemic plasma, 1394 polypeptides were detected in the high-flux vs 1046 in the low-flux samples, while in ultrafiltrate from normal plasma, 544 polypeptides vs 490 were found in ultrafiltrate from normal plasma obtained from membranes with comparable cut-off. In addition, polypeptides >5 kDa were virtually only detected in the uraemic ultrafiltrate from the high-flux membrane (n = 28 vs n = 5 with the low-flux membrane). To demonstrate the feasibility of further characterizing the detected molecules, polypeptides present exclusively in uraemic ultrafiltrate were chosen for sequencing analyses. A 950.6 Da polypeptide was identified as a fragment of the salivary proline-rich protein. A 1291.8 Da fragment was derived from alpha-fibrinogen., Conclusion: The data presented here strongly suggest that the application of proteomic approaches such as capillary electrophoresis and mass spectrometry will result in the identification of many more uraemic solutes than those known at present. This could enable the introduction of more direct elimination strategies, since it is possible to obtain an extended appreciation of the removal capacities of particular dialyser membranes.

Background: The blunted immune response upon stimulation in chronic renal failure (CRF) is often coupled to a baseline inflammatory status which has been related to atherogenesis. Uremic biologic fluids and several specific uremic retention solutes alter cell-mediated immune responses, as well as the interaction of calcitriol with the immune system., Methods: The present study evaluated the influence of different guanidino compounds on DNA synthesis, chemiluminescence production, and CD14 expression of undifferentiated and calcitriol-differentiated HL-60 cells. In a second setup, these guanidino compounds were evaluated for their specific effect on normal human leukocyte oxidative burst activity and tumor necrosis factor-alpha (TNF-alpha) expression., Results: First, several guanidino compounds elicited proinflammatory effects on leukocytes. Methylguanidine and guanidine stimulated the proliferation of undifferentiated HL-60 cells and the antiproliferative effect of calcitriol (P < 0.05) was neutralized in the presence of methylguanidine (P < 0.05) and guanidinosuccinic acid (P < 0.05). The phorbol-myristate-acetate (PMA)-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was enhanced in the presence of guanidine (P < 0.05). Methylguanidine and guanidinoacetic acid enhanced the lipopolysaccharide (LPS)-stimulated intracellular production of TNF-alpha by normal human monocytes (P < 0.05). Second, several guanidino compounds inhibited the function of leukocytes if they were activated. The PMA-stimulated chemiluminescence production of the calcitriol differentiated HL-60 cells was inhibited by the presence of methylguanidine (P < 0.05), guanidinoacetic acid (P < 0.05) and guanidinosuccinic acid (P < 0.05). After incubation of whole blood in the presence of methylguanidine, the Escherichia coli stimulated oxidative burst activity of the granulocyte population was significantly inhibited (P < 0.05). In addition, guanidinosuccinic acid had an inhibitory effect on the LPS-stimulated intracellular production of TNF-alpha by human monocytes (P < 0.01)., Conclusion: Guanidino compounds exert proinflammatory as well as anti-inflammatory effects on monocyte/macrophage function. This could contribute to the altered prevalence of cardiovascular disease and propensity to infection in patients with CRF.

Critically ill patients with acute renal failure (ARF) treated with renal replacement therapy (RRT) have a high mortality. The authors evaluated a cohort of 704 consecutive intensive care unit (ICU) patients with ARF treated with RRT to determine whether there was an increased incidence of nosocomial bloodstream infection and whether this resulted in a worse outcome. The incidence of nosocomial bloodstream infection was 8.8%, higher than that reported in other series of general ICU patients and also higher than the 3.5% incidence of bloodstream infection in non-ARF patients in the same unit (P < 0.001). There were more bloodstream infections caused by Gram-positive species compared with Gram-negative species or fungi. The distribution over the species was comparable to that reported by others for a general ICU population. The outcome was evaluated with matched cohort analysis. With this technique, patients with bloodstream infection (exposed) were closely matched with patients without bloodstream infection (non-exposed) in a 1:2 ratio. Matching was based on the APACHE II system and length of stay before bloodstream infection (exposure time). Length of stay and mortality were equal in exposed and non-exposed patients. There was also no difference in hospital costs. It can be concluded that critically ill patients with ARF treated with RRT were more susceptible to nosocomial bloodstream infection. Nevertheless, the outcome was not influenced by the presence of bloodstream infection. The high mortality observed in ARF patients could therefore not be attributed to the higher incidence of bloodstream infection.

The uremic syndrome is the result of the retention of solutes, which under normal conditions are cleared by the healthy kidneys. Uremic retention products are arbitrarily subdivided according to their molecular weight. Low-molecular-weight molecules are characterized by a molecular weight below 500 D. The purpose of the present publication is to review the main water soluble, nonprotein bound uremic retention solutes, together with their main toxic effects. We will consecutively discuss creatinine, glomerulopressin, the guanidines, the methylamines, myo-inositol, oxalate, phenylacetyl-glutamine, phosphate, the polyamines, pseudouridine, the purines, the trihalomethanes, and urea per se.

Acute renal failure (ARF) is a common complication in intensive care unit (ICU) patients. Although there are several reports on outcome of septic patients with ARF, there are no data regarding predisposing factors for ARF. Therefore, the incidence of ARF was investigated in 185 sepsis patients admitted in a surgical ICU during a 16-mo period. Variables predisposing to ARF on day 1 of sepsis were evaluated with univariate and multivariable analyses. APACHE II and SOFA scores were compared during a 14-d period. Additionally, the impact of organ failure on mortality was evaluated. ARF developed in 16.2% of the patients, and 70.0% of these needed renal replacement therapy (RRT). Patients with ARF were more severely ill and had a higher mortality. Remarkably, serum creatinine was already increased on day 1. Creatinine > 1 mg/dl and pH < 7.30, both on day 1 of sepsis, were independently associated with ARF. Age, need for vasoactive therapy, mechanical ventilation, and RRT, but not ARF itself, were associated with mortality. In conclusion, ARF was a frequent complication in sepsis. Sepsis patients with ARF were more severely ill and had a higher mortality. Need for RRT was independently associated with mortality. A simple risk model for ARF, on basis of two readily available parameters on day 1 of sepsis, was developed. This model allows initiating specific therapeutic measures earlier in the course of sepsis, hopefully resulting in a lower incidence of ARF and needi for RRT, thereby lowering mortality.

A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules (>500 Da). The prototype of small water-soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water-soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra-dialytic behavior, which is different from that of urea. In addition, the protein-bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high-flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination.

About 100 uremic retention solutes have been identified at present, but not all of these compounds are necessarily toxic. They can be defined as uremic toxins if they exert biochemical/biological actions. Based on their physicochemical characteristics, there are three major groups of uremic retention solutes: 1) the small water-soluble compounds (<500 Da), which are easily removed by standard low-pore-size dialyzer membranes; 2) the protein-bound solutes (also mostly <500 Da), whose dialytic removal is hampered by their protein binding, irrespective of the membrane type; and 3) the so-called middle molecules (>500 Da), which can be removed only by membranes with a large pore size and/or adsorptive capacity. In the present review, we will summarize the currently known information about the toxicity of the uremic retention solutes. Although removal of small water-soluble urea has been recognized for many years as a current measure of dialysis adequacy, data on its toxicity are very scanty. Almost 50 other water-soluble compounds are known to be retained in uremia, but only a few exert biological effects. Most of the toxic water-soluble moieties, such as the guanidines, phosphate, xanthine, and hypoxanthine show an intra-dialytic compartmental behavior, which is different from urea. A substantial number of uremic solutes are protein bound, and most of them exert biological action. Among them are the phenols, indoles, homocysteine, and carboxy-methyl-propyl-furanpropionic acid. Recent data suggest that protein binding acts as a buffer against the toxic effects of these compounds, and that hypoalbuminemia increases both their free fraction and their toxicity. In addition, many middle molecules, such as ss(2)-microglobulin, leptin, and advanced glycation end products, have been related to biological/clinical effects. Our current knowledge of the biological impact of the middle molecules is very likely incomplete. It is concluded that many of the water-soluble compounds exert little or no toxicity, and that urea removal pattern per se is not identical to that of many biologically active molecules. Hence, in dialysis, more than urea removal alone should be pursued.

Background: The Genius single-pass batch system for hemodialysis contains a closed reservoir and dialysate circuit of 75 L dialysate. The unused dialysate is withdrawn at the top of the reservoir and the spent fluid is reintroduced into the container at the bottom. Although it has been claimed that both fractions remain unmixed during the dialysis session, no direct proof of this assumption has yet been provided. In the present study, we investigated whether contamination of the unused dialysate with uremic solutes occurred and at which time point it began. Two different dialysate temperatures were compared., Methods: Ten chronic hemodialysis patients were dialyzed twice with the Genius system, with dialysate prepared at 37 degrees C and 38.5 degrees C, respectively. The sessions lasted 270 minutes with blood/dialysate flow set at 300 mL/min. Dialysate was sampled at 5, 60, 180, 210, 225, 230, 235, 240, 255, and 270 minutes both from the inlet and outlet dialysate line and blood was sampled from the arterial line predialysis, after 4 hours, and postdialysis. All samples were tested for osmolality, urea, creatinine, p-cresol, hippuric acid, and indoxyl sulfate., Results: Uremic solutes appeared in the inlet dialysate line between 3 hours 50 minutes and 4 hours 10 minutes after the start of dialysis, corresponding to 68.6 and 74.7 L spent dialysate, respectively (37 degrees C vs. 38.5 degrees C; P = NS). No difference in the amount of removed solutes and in the serum levels was observed between 37 degrees C and 38.5 degrees C. A Kt/V of 1.17 +/- 0.20 and 1.18 +/- 0.26, respectively, was reached with the 37 degrees C and 38.5 degrees C dialysate temperature (P = NS)., Conclusion: Contamination with uremic solutes occurred at the dialysate inlet only near the end of the session when small quantities of fresh dialysate were left in the container. Differences in dialysate temperature did not result in a different separation between used and unused dialysate, or in differences in removal of toxins or Kt/V.

Middle molecules can be defined as compounds with a molecular weight (MW) above 500 Da. An even broader definition includes those molecules that do not cross the membranes of standard low-flux dialyzers, not only because of molecular weight, but also because of protein binding and/or multicompartmental behavior. Recently, several of these middle molecules have been linked to the increased tendency of uremic patients to develop inflammation, malnutrition, and atheromatosis. Other toxic actions can also be attributed to the middle molecules. In the present publication we will consider whether improved removal of middle molecules by large pore membranes has an impact on clinical conditions related to the uremic syndrome. The clinical benefits of large pore membranes are reduction of uremia-related amyloidosis; maintenance of residual renal function; and reduction of inflammation, malnutrition, anemia, dyslipidemia, and mortality. It is concluded that middle molecules play a role in uremic toxicity and especially in the processes related to inflammation, atherogenesis, and malnutrition. Their removal seems to be related to a better outcome, although better biocompatibility of membranes might be a confounding factor.

Background: There is debate as to whether, in patients with acute lung injury, continuous renal replacement therapy has beneficial effects on pulmonary gas exchange by mechanisms other than fluid removal. Because continuous renal replacement therapy is associated with potential morbidity and mortality, it seems unethical to perform a randomized trial in patients with acute lung injury without renal failure. Therefore, the effects of continuous venovenous haemodiafiltration with zero volume balance on gas exchange were evaluated in patients with acute renal failure and acute lung injury. Because haemofilter conditions should be comparable between patients, we opted for an evaluation of the effects during a 24-h period. Results of this trial can guide future studies in non-renal patients with acute lung injury., Methods: In all 37 patients with acute renal failure and acute lung injury, treated with continuous venovenous haemodiafiltration with zero fluid balance during a 1 year period, ventilatory and haemodynamic parameters were measured every 8 h during the 24 h preceding therapy and during the first 24 h of therapy., Results: We found a slight, although not statistically significant, increase in the PaO(2)/FIO(2) ratio and the oxygenation index, in the total group of patients, and in the subgroups of patients with acute lung injury of extrapulmonary and pulmonary causes., Conclusions: During the first 24 h of treatment, continuous venovenous haemodiafiltration with zero volume balance did not result in a significant improvement of the respiratory status in patients with acute renal failure and acute lung injury, nor in the subgroups of patients with acute lung injury with extrapulmonary causes.

Objective: Peritoneal dialysis (PD) patients frequently suffer from dyspeptic complaints such as nausea, vomiting, abdominal distension, early satiety, and anorexia. Gastroparesis might be, at least partially, a source of dyspeptic complaints in PD patients. The aim of the present study was to determine the influence of the presence and composition of dialysate on gastric emptying in PD patients., Design: Prospective study., Setting: Renal Division, Department of Internal Medicine, Ghent University Hospital, Belgium., Patients: Sixty-one PD patients using different dialysate solutions, and 27 healthy volunteers., Main Outcome Measure: Gastric emptying of solids was assessed by the 13C-octanoic acid breath test., Results: Gastric emptying was impaired in PD patients, regardless of the composition of dialysate and even if tested with an empty peritoneal cavity. Gastric emptying was significantly slower when glucose-containing dialysate was compared to an empty peritoneal cavity, or when glucose-containing dialysate was compared to icodextrin dialysate. No difference in gastric emptying could be demonstrated between glucose-containing dialysate and dialysate containing a mixture of glycerol and amino acids as osmotic agent., Conclusions: These findings suggest that the delay in gastric emptying demonstrated in the presence of peritoneal dialysate is not the consequence of a mere volume or pressure effect, but of the absorption of substrate substances with caloric and/or metabolic activity, such as glucose or glycerol and amino acids.

Studies analyzing the outcome of integrative care of end-stage renal disease (ESRD) patients, whereby patients are transferred from one renal replacement modality to another according to individual needs, are scant. In this study, we analyzed 417 files of 223 hemodialysis (HD) and 194 peritoneal dialysis (PD) patients starting renal replacement therapy between 1979 and 1996, to evaluate the effect of such an approach. Analysis was done for survival of patients on their first modality, for intention-to-treat survival (counting total time on renal replacement therapy, but with exclusion of time on transplantation), and for total survival. Log rank analysis was used and correction for risk factors was performed by Cox proportional hazards regression. Intention-to-treat survival and total survival were not different between PD and HD patients (log rank, P > 0.05). Technique success was higher in HD patients compared to PD patients (log rank, P = 0.01), with a success rate after 3 yr of 61 and 48%, respectively. Thirty-five patients were transferred from HD to PD and 32 from PD to HD. Transfer of PD patients to HD was accompanied by an increase in survival compared to those remaining on PD (log rank, P = 0.001), whereas, in contrast, transfer of patients from HD to PD was not (log rank, P = 0.17). Survival of patients remaining more than 48 mo on their initial modality was lower for PD patients (log rank, P < 0.01). A matched-pair analysis between patients who started on PD and who were transferred to HD later (by definition called integrative care patients), and patients who started and remained on HD, showed a survival advantage for the integrative care patients. These results indicate that patient outcome is not jeopardized by starting patients on PD, at least if patients are transferred in a timely manner to HD when PD-related problems arise.

A potential application of the continuous renal replacement therapies is the extracorporeal removal of inflammatory mediators in septic patients. Cytokine elimination with continuous renal replacement therapies has been demonstrated in several clinical studies, but so far without important effects on their serum concentrations. Improved knowledge of the cytokine removal mechanisms could lead to the development of more efficient treatment strategies. In the present study, 15 patients with septic shock and acute renal failure were observed during the first 24 h of treatment with continuous venovenous hemofiltration (CVVH) with an AN69 membrane. After 12 h, the hemofilter was replaced and the blood flow rate (QB) was switched from 100 ml/min to 200 ml/min or vice versa. Pre- and postfilter plasma and ultrafiltrate concentrations of selected inflammatory and anti-inflammatory cytokines were measured at several time points allowing the calculation of a mass balance. Cytokine removal was highest 1 h after the start of CVVH and after the change of the membrane (ranging from 25 to 43% of the prefilter amount), corresponding with a significant fall in the serum concentration of all cytokines. The inhibitors of inflammation were removed to the same extent as the inflammatory cytokines. Adsorption to the AN69 membrane appeared to be the main clearance mechanism, being most pronounced immediately after installation of a new membrane and decreasing steadily thereafter, indicating rapid saturation of the membrane. A QB of 200 ml/min was associated with a 75% increase of the ultrafiltration rate and a significantly higher convective elimination and membrane adsorption than at a QB of 100 ml/min. The results indicate that optimal cytokine removal with CVVH with an AN69 membrane could be achieved with a combination of a high QB/ultrafiltration rate and frequent membrane changes.

The influence of the pretransplantation hemodialysis strategy on early renal graft function was evaluated in 44 patients receiving hemodialysis in the 24 h preceding kidney transplantation and in 13 patients receiving hemodialysis more than 24 h before transplantation. The patients dialyzed less than 24 h before transplantation were stratified according to treatment with or without complement-activating dialyzers (cuprophane, bioincompatible membrane [BICM] versus polysulfone, biocompatible membrane [BCM]) and with or without ultrafiltration (UF). Serum creatinine (Scr) at days 0, 2, 5, 10, and 30, the time for Scr to decrease 50% (T1/2Scr), the incidence of acute renal failure (ARF; defined as urinary volume < 500 ml/d and/or necessity for posttransplantation hemodialysis), and early graft dysfunction (defined as T1/2Scr > 3.5 d) were registered. Scr was higher in BCM- versus BICM-treated patients (P < 0.0001 by variance analysis) and in patients receiving UF versus those receiving no UF (P = 0.0009). T1/2Scr was higher in treatment with BICM versus BCM (7.4 +/- 7.9 versus 3.1 +/- 2.9 d; P < 0.05) and UF versus no UF (7.1 +/- 7.7 versus 2.7 +/- 2.0 d; P < 0.01). The evolution of Scr was markedly more favorable in the patient group treated with BCM without UF (T1/2Scr 1.7 +/- 0.8 d) compared with the group treated with BICM and UF (T1/2Scr 9.3 +/- 9.1 d; P < 0.01). The remaining groups (BICM without UF and BCM with UF) showed intermediate results. The incidence of ARF and early graft dysfunction was higher in the group on BICM with UF compared to BCM without UF. Functional differences persisted up to 1 mo after transplantation. Patients who underwent dialysis with UF more than 24 h before transplantation had a more beneficial evolution of renal function parameters than those who were dialyzed with UF less than 24 h before transplantation. In conclusion, the use of BICM and the application of UF within 24 h before kidney transplantation enhance the risk of posttransplantation ARF and early graft dysfunction.

The expression of CD14 on monocytes and CD45 on monocytes and granulocytes was evaluated during hemodialysis by flow cytometric analysis in the 'resting state' and after in vitro stimulation with phorbol myristate acetate (PMA). A comparison of complement activating cuprophane (CU) versus less complement activating polysulfone (PS) was undertaken. 'Resting state' CD45 expression on granulocytes increased markedly during CU dialysis compared to time 0, whereas this rise was only moderate with PS (CU vs. PS, p < 0.01). When considering the increase in expression upon PMA stimulation, a lower value was obtained during CU dialysis for both CD14 (monocytes at 60 and 240 min) and for CD45 (monocytes and granulocytes at 15 min). In conclusion, granulocytes in the 'resting state' expressed more CD45 on their cell membranes during CU dialysis, whereas CD14 and CD45 upregulation after ex vivo addition of PMA was blunted during CU dialysis.