Factors influencing kidney transplantation rates: a study from the ERA Registry.

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.

Our shared responsibility: the urgent necessity of global environmentally sustainable kidney care.

In response to Earth's accelerating climate crisis, we, an international group of nephrologists, call on our global community to unite and align kidney care in accordance with United Nation's 26th Conference of the Parties health sector principles. We announce a global and inclusive initiative, "GREEN-K": Global Environmental Evolution in Nephrology and Kidney Care, with a vision of "sustainable kidney care for a healthy planet and healthy kidneys" and mission to "promote and support environmentally sustainable and resilient kidney care globally through advocacy, education, and collaboration." A patient-centric approach that permits climate change mitigation and adaptation is proposed. Multi-stakeholder GREEN-K action and focus areas will include education, sustainable clinical care, and advances toward environmentally sustainable innovations, procurement, and infrastructure. Mindful of the disproportionately high climate impact of kidney therapies, we welcome the opportunity to work together in shared accountability to patients and Earth's natural systems.

Patient-reported factors influencing the choice of their kidney replacement treatment modality.

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.

International Society of Nephrology Global Kidney Health Atlas: structures, organization, and services for the management of kidney failure in Western Europe.

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.

Results of the European EDITH nephrologist survey on factors influencing treatment modality choice for end-stage kidney disease.

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.

Supplemented ERA-EDTA Registry data evaluated the frequency of dialysis, kidney transplantation, and comprehensive conservative management for patients with kidney failure in Europe.

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.

Inflammation and Erythropoiesis-Stimulating Agent Response in Hemodialysis Patients: A Self-matched Longitudinal Study of Anemia Management in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

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.

Association between changes in quality of life and mortality in hemodialysis patients: results from the DOPPS.

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.

Future Avenues to Decrease Uremic Toxin Concentration.

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.

Associations of self-reported physical activity types and levels with quality of life, depression symptoms, and mortality in hemodialysis patients: the DOPPS.

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.

Disaster nephrology: crush injury and beyond.

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.

Fondaparinux as an alternative to vitamin K antagonists in haemodialysis patients.

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.

How to use biomarkers efficiently in acute kidney injury.

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.

Hurricane Katrina and chronic dialysis patients: better tidings than originally feared?

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.

Epidemiology of infection in critically ill patients with acute renal failure.

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.

Evaluation of urine proteome pattern analysis for its potential to reflect coronary artery atherosclerosis in symptomatic patients.

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.

Exploring the uremic toxins using proteomic technologies.

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.