Derivation and External Validation of a Risk Index for Predicting Acute Kidney Injury Requiring Kidney Replacement Therapy After Noncardiac Surgery.

Importance: Severe acute kidney injury (AKI) is a serious postoperative complication. A tool for predicting the risk of AKI requiring kidney replacement therapy (KRT) after major noncardiac surgery might assist with patient counseling and targeted use of measures to reduce this risk. Objective: To derive and validate a predictive model for AKI requiring KRT after major noncardiac surgery. Design, Setting, and Participants: In this prognostic study, 5 risk prediction models were derived and internally validated in a population-based cohort of adults without preexisting kidney failure who underwent noncardiac surgery in Alberta, Canada, between January 1, 2004, and December 31, 2013. The best performing model and corresponding risk index were externally validated in a population-based cohort of adults without preexisting kidney failure who underwent noncardiac surgery in Ontario, Canada, between January 1, 2007, and December 31, 2017. Data analysis was conducted from September 1, 2019, to May 31, 2021. Exposures: Demographic characteristics, surgery type, laboratory measures, and comorbidities before surgery. Main Outcomes and Measures: Acute kidney injury requiring KRT within 14 days after surgery. Discrimination was assessed using the C statistic; calibration was assessed using calibration intercept and slope. Logistic recalibration was used to optimize model calibration in the external validation cohort. Results: The derivation cohort included 92 114 patients (52.2% female; mean [SD] age, 62.3 [18.0] years), and the external validation cohort included 709 086 patients (50.8% female; mean [SD] age, 61.0 [16.0] years). A total of 529 patients (0.6%) developed postoperative AKI requiring KRT in the derivation cohort, and 2956 (0.4%) developed postoperative AKI requiring KRT in the external validation cohort. The following factors were consistently associated with the risk of AKI requiring KRT: younger age (40-69 years: odds ratio [OR], 2.07 [95% CI, 1.69-2.53]; <40 years: OR, 3.73 [95% CI, 2.61-5.33]), male sex (OR, 1.55; 95% CI, 1.28-1.87), surgery type (colorectal: OR, 4.86 [95% CI, 3.28-7.18]; liver or pancreatic: OR, 6.46 [95% CI, 3.85-10.83]; other abdominal: OR, 2.19 [95% CI, 1.66-2.89]; abdominal aortic aneurysm repair: OR, 19.34 [95% CI, 14.31-26.14]; other vascular: OR, 7.30 [95% CI, 5.48-9.73]; thoracic: OR, 3.41 [95% CI, 2.07-5.59]), lower estimated glomerular filtration rate (OR, 0.97; 95% CI, 0.97-0.97 per 1 mL/min/1.73 m2 increase), lower hemoglobin concentration (OR, 0.99; 95% CI, 0.98-0.99 per 0.1 g/dL increase), albuminuria (mild: OR, 1.88 [95% CI, 1.52-2.33]; heavy: OR, 3.74 [95% CI, 2.98-4.69]), history of myocardial infarction (OR, 1.63; 95% CI, 1.32-2.03), and liver disease (mild: OR, 2.32 [95% CI, 1.66-3.24]; moderate or severe: OR, 4.96 [95% CI, 3.58-6.85]). In external validation, a final model including these variables showed excellent discrimination (C statistic, 0.95; 95% CI, 0.95-0.96), with sensitivity of 21.2%, specificity of 99.9%, positive predictive value of 38.1%, and negative predictive value of 99.7% at a predicted risk threshold of 10% or greater. Conclusions and Relevance: The findings suggest that this risk model can predict AKI requiring KRT after noncardiac surgery using routine preoperative data. The model may be feasible for implementation in clinical perioperative risk stratification for severe AKI.

Assessing Nephrology Fellows' Skills in Communicating About Kidney Replacement Therapy and Kidney Biopsy: A Multicenter Clinical Simulation Study on Breaking Bad News.

RATIONALE & OBJECTIVE: Interpersonal communication skills and professionalism competencies are difficult to assess among nephrology trainees. We developed a formative "Breaking Bad News" simulation and implemented a study in which nephrology fellows were assessed with regard to their skills in providing counseling to simulated patients confronting the need for kidney replacement therapy (KRT) or kidney biopsy. STUDY DESIGN: Observational study of communication competency in the setting of preparing for KRT for kidney failure, for KRT for acute kidney injury (AKI), or for kidney biopsy. SETTING & PARTICIPANTS: 58 first- and second-year nephrology fellows assessed during 71 clinical evaluation sessions at 8 training programs who participated in an objective structured clinical examination of simulated patients in 2017 and 2018. PREDICTORS: Fellowship training year and clinical scenario. OUTCOME: Primary outcome was the composite score for the "overall rating" item on the Essential Elements of Communication-Global Rating Scale 2005 (EEC-GRS), as assessed by simulated patients. Secondary outcomes were the score for EEC-GRS "overall rating" item for each scenario, score < 3 for any EEC-GRS item, Mini-Clinical Examination Exercise (Mini-CEX) score < 3 on at least 1 item (as assessed by faculty), and faculty and fellow satisfaction with simulation exercise (via a survey they completed). ANALYTICAL APPROACH: Nonparametric tests of hypothesis comparing performance by fellowship year (primary goal) and scenario. RESULTS: Composite scores for EEC-GRS overall rating item were not significantly different between fellowship years (P = 0.2). Only 4 of 71 fellow evaluations had an unsatisfactory score for the EEC-GRS overall rating item on any scenario. On Mini-CEX, 17% scored < 3 on at least 1 item in the kidney failure scenario; 37% and 53% scored < 3 on at least 1 item in the AKI and kidney biopsy scenarios, respectively. In the survey, 96% of fellows and 100% of faculty reported the learning objectives were met and rated the experience good or better in 3 survey rating questions. LIMITATIONS: Relatively brief time for interactions; limited familiarity with and training of simulated patients in use of EEC-GRS. CONCLUSIONS: The fellows scored highly on the EEC-GRS regardless of their training year, suggesting interpersonal communication competency is achieved early in training. The fellows did better with the kidney failure scenario than with the AKI and kidney biopsy scenarios. Structured simulated clinical examinations may be useful to inform curricular choices and may be a valuable assessment tool for communication and professionalism.

Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.

BACKGROUND: Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation. METHODS: We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I2 values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive. RESULTS: Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94-1.09; P = 0.77; I2 = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23-1.63; P < 0.00001; I2 = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01-1.78; P = 0.04; I2 = 0%). CONCLUSIONS: This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.

Palliative Renal Care and the Covid-19 Pandemic.

INTRODUCTION: Palliative care is an approach aimed at relieving suffering, controlling symptoms and seeking to improve quality of life. It must be offered in conjunction with standard treatment for any disease that threatens the continuation of life, such as a Covid-19 infection. DISCUSSION: The bioethical principles and strategies used by palliative medicine can assist nephrologists in the care of patients with renal dysfunction, who face the difficulties of isolation at the beginning and follow-up of dialysis in outpatient treatment, and those who are at risk for a more serious disease progress. Some of them: - a Shared decision making, which enables the patient and family to participate as facilitators in the systematization of the team's reasoning, in addition to respecting the principle of autonomy; - Symptom Management: which should be a priority to ensure relief of suffering even in times of social isolation; - Communication skills: making it possible to alleviate suffering in announcing bad news or complex decisions through communication techniques;; - Bereavement assistance: which in acute situations such as the pandemic, causing unexpected losses, the importance of sympathy from healthcare professionals becomes even greater. CONCLUSION: The principles of palliative care are essential to face the challenges of a planet-wide crisis, which raises human suffering in all dimensions, and which requires the construction of strategies that can keep patients assisted, comfortable and with measures proportional to their clinical condition and preferences.

Timing of initiation of renal replacement therapy in acute kidney injury: an updated meta-analysis of randomized controlled trials.

Purpose: The results from randomized controlled trials (RCTs) concerning the timing of initiation of renal replacement therapy (RRT) for patients with acute kidney injury (AKI) are still inconsistent.Materials and methods: We searched for RCTs, as well as relevant references, focusing on the timing of RRT for AKI patients in the Medline, Embase, Cochrane Library, Google Scholar and Chinese databases from their inception to December 2018.Results: We included 18 RCTs from 1997 to 2018 involving 2856 patients. Pooled analyses of all RCTs showed no significant difference in mortality between early initiation and delayed initiation of RRT (RR 0.98, 95% CI: 0.89 to 1.08, p = .7) (I2 = 2%), and similar results were found in critically ill and community-acquired AKI patients, as well as in a subgroup of patients with sepsis and in cardiac surgery recipients. There was also no difference in the incidence of dialysis independence (RR 0.75, 95% CI: 0.47 to 1.2, p = .2) (I2 = 0). However, an early RRT strategy was associated with a significantly higher incidence of the need for RRT for AKI patients (RR 1.24, 95% CI: 1.13 to 1.36, p < .01) (I2 = 34%).Conclusions: As no life-threatening complications occurred, there was no evidence to show any benefit of an early RRT strategy for critically ill or community-acquired AKI patients; in contrast, a delayed strategy might avert the need for RRT.

Technical note and clinical instructions for Acute Kidney Injury (AKI) in patients with Covid-19: Brazilian Society of Nephrology and Brazilian Association of Intensive Care Medicine / Nota técnica e orientações clínicas sobre a Injúria Renal Aguda (IRA) em pacientes com Covid-19: Sociedade Brasileira de Nefrologia e Associação de Medicina Intensiva Brasileira

ABSTRACT We produced this document to bring pertinent information to the practice of nephrology, as regards to the renal involvement with COVID-19, the management of acute kidney injury cases, and practical guidance on the provision of dialysis support.As information on COVID-19 evolves at a pace never before seen in medical science, these recommendations, although based on recent scientific evidence, refer to the present moment. The guidelines may be updated when published data and other relevant information become available.

RESUMO Este documento foi desenvolvido para trazer informações pertinentes à prática nefrológica em relação ao conhecimento sobre o acometimento renal da COVID-19, conduta frente aos casos de injúria renal aguda e orientações práticas sobre a provisão do suporte dialítico.Como as informações sobre a COVID-19 evoluem a uma velocidade jamais vista na ciência médica, as orientações apresentadas, embora baseadas em evidências científicas recentes, referem-se ao momento presente. Essas orientaços poderão ser atualizadas à medida que dados publicados e outras informações relevantes venham a ser disponibilizadas.

Palliative renal care and the covid-19 pandemic / Cuidado paliativo renal e a pandemia de Covid-19

ABSTRACT Introduction Palliative care is an approach aimed at relieving suffering, controlling symptoms and seeking to improve quality of life. It must be offered in conjunction with standard treatment for any disease that threatens the continuation of life, such as a Covid-19 infection. Discussion The bioethical principles and strategies used by palliative medicine can assist nephrologists in the care of patients with renal dysfunction, who face the difficulties of isolation at the beginning and follow-up of dialysis in outpatient treatment, and those who are at risk for a more serious disease progress. Some of them: - a Shared decision making, which enables the patient and family to participate as facilitators in the systematization of the team's reasoning, in addition to respecting the principle of autonomy; - Symptom Management: which should be a priority to ensure relief of suffering even in times of social isolation; - Communication skills: making it possible to alleviate suffering in announcing bad news or complex decisions through communication techniques;; - Bereavement assistance: which in acute situations such as the pandemic, causing unexpected losses, the importance of sympathy from healthcare professionals becomes even greater. Conclusion The principles of palliative care are essential to face the challenges of a planet-wide crisis, which raises human suffering in all dimensions, and which requires the construction of strategies that can keep patients assisted, comfortable and with measures proportional to their clinical condition and preferences.

RESUMO Introdução O cuidado paliativo é uma abordagem voltada para alívio do sofrimento, controle de sintomas e melhora da qualidade de vida. Deve ser oferecido em conjunto com o tratamento padrão de qualquer doença que ameace a continuidade da vida, como, por exemplo, a infecção pela Covid-19. Discussão Os princípios bioéticos e as estratégias utilizadas pela medicina paliativa podem auxiliar os nefrologistas no cuidado dos pacientes com disfunção renal, que, além de serem do grupo de risco para evolução mais grave da infecção por coronavírus, enfrentam as dificuldades do isolamento no seguimento do tratamento dialítico e ambulatorial. Essas ferramentas são: I) tomada de decisão compartilhada, que proporciona a participação do paciente e dos familiares como facilitadores na sistematização do raciocínio da equipe, além de respeitar o princípio da autonomia; II) manejo de sintomas, que deve ser prioridade para a garantia do alívio do sofrimento mesmo em momento de isolamento social; III) habilidades em comunicação, sendo possível amenizar dificuldades em anunciar más notícias ou decisões complexas através de técnicas de comunicação; IV) assistência ao luto, em que, em situações agudas como a pandemia, de perdas inesperadas, a importância do acolhimento dos profissionais de saúde torna-se ainda maior. Conclusão Os princípios dos cuidados paliativos são essenciais para enfrentar os desafios de uma crise humanitária, que causa sofrimento ao ser humano em todas as dimensões e exige a construção de estratégias que possam manter os pacientes assistidos, confortáveis e com medidas proporcionais à sua condição clínica e às suas preferências.

Recommendations of the brazilian society of nephrology regarding pediatric patients on renal replacement therapy during the covid-19 pandemic / Recomendações da sociedade brasileira de nefrologia para pacientes pediátricos em terapia de substituição renal durante a pandemia de covid-19

ABSTRACT Introduction The impact of the new coronavirus (SARS-COV-2) and its worldwide clinical manifestations (COVID-19) imposed specific regional recommendations for populations in need of specialized care, such as children and adolescents with kidney diseases, particularly in renal replacement therapies (RRT). We present the recommendations of the Brazilian Society of Nephrology regarding the treatment of pediatric patients with kidney diseases during the COVID-19 pandemic. Methods Articles and documents from medical societies and government agencies on specific recommendations for children on RRT in relation to COVID-19 as well as those focused on epidemiological aspects of this condition in Brazil Were evaluated and analyzed. Results We present recommendations on outpatient care, transportation to dialysis centers, peritoneal dialysis, hemodialysis, and kidney transplantation in children and adolescents during the COVID-19 pandemic in Brazil. Discussion Despite initial observations of higher mortality rates in specific age groups (the elderly) and with comorbidities (obese, diabetics, and those with cardiovascular diseases), patients with chronic kidney disease (CKD) on RRT are particularly prone to develop COVID-19. Specific measures must be taken to reduce the risk of contracting SARS-CoV-2 and developing COVID-19, especially during transport to dialysis facilities, as well as on arrival and in contact with other patients.

RESUMO Introdução O impacto do novo coronavírus (SARS-CoV-2) e as suas manifestações clínicas (Covid-19) em todo o mundo impôs recomendações regionais específicas a populações que necessitam de cuidados especializados, como crianças e adolescentes com doenças renais, particularmente em terapias de substituição renal (TRS). Apresentamos as recomendações da Sociedade Brasileira de Nefrologia em relação ao tratamento de pacientes pediátricos com doenças renais durante a pandemia Covid-19. Método Foram avaliados e analisados os artigos e documentos sobre recomendações específicas para Covid-19 de sociedades médicas e órgãos governamentais sobre crianças em TRS, bem como aqueles focados em aspectos epidemiológicos dessa condição no Brasil. Resultados Apresentamos as recomendações sobre atendimento ambulatorial, transporte para centros de diálise, diálise peritoneal, hemodiálise e transplante renal em crianças e adolescentes durante a pandemia de Covid-19 no Brasil. Discussão Apesar das observações iniciais de taxas de mortalidade mais altas em grupos etários específicos (idosos) e com comorbidades (obesos, diabéticos e aqueles com doenças cardiovasculares), pacientes com doença renal crônica (DRC) em TRS apresentam risco significativo de evoluir com Covid-19. Medidas específicas devem ser tomadas para reduzir o risco de contrair SARS-CoV-2 e desenvolver a Covid-19, principalmente durante o transporte para instalações de diálise, bem como na chegada e no contato com outros pacientes.

Temporal change in characteristics and outcomes of acute kidney injury on renal replacement therapy in intensive care units: analysis of a nationwide administrative database in Japan, 2007-2016.

BACKGROUND: We aimed to examine recent trends in patient characteristics and mortality in patients with acute kidney injury (AKI) receiving renal replacement therapy (RRT), including continuous RRT (CRRT) and intermittent RRT (IRRT), in intensive care units (ICUs). METHODS: From the Diagnosis Procedure Combination database in Japan during 6 months (July-December) from 2007 to 2016, we identified patients with AKI who received RRT in ICUs. We restricted the study participants to those admitted to hospitals (in which both CRRT and IRRT were available) that participated in the Diagnosis Procedure Combination database for all 10 years. We examined the trends in patient characteristics and mortality overall, by RRT modality, and by main diagnosis category subgroup. Logistic regression was used to adjust for patient characteristics. RESULTS: We identified 51,758 patients starting RRT in 287 hospitals, including 39,471 (76.3%) and 12,287 (23.7%) patients starting CRRT and IRRT. The crude in-hospital mortality declined from 44.9 to 36.1% (P for trend < 0.001). Compared with 2007, the adjusted odds ratio (aOR) for in-hospital mortality was 0.66 (95% confidence interval (CI) 0.60-0.72) in 2016, and the decreasing trend was observed in both patients starting CRRT (aOR 0.67, 95% CI 0.61-0.75) and IRRT (0.58, 0.45-0.74), and in all subgroups except for coronary artery disease: sepsis aOR 0.68 (95% CI 0.57-0.81); cardiovascular surgery 0.58 (0.45-0.76); coronary artery disease 0.84 (0.60-1.19); non-coronary heart disease 0.78 (0.64-0.94); central nervous system disorders 0.42 (0.28-0.62); trauma 0.39 (0.21-0.72); and other 0.64 (0.50-0.82). CONCLUSIONS: This nationwide study confirmed a consistent decline in mortality among patients with AKI on RRT in ICUs. The adjusted mortality also declined during the study period; however, physiological variables were not measured in this study and it is possible that RRT may have been indicated for patients with less severe AKI in more recent years.

Permissive fluid volume in adult patients undergoing extracorporeal membrane oxygenation treatment.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a cardiorespiratory support technique for patients with circulatory or pulmonary failure. Frequently, large-volume fluid resuscitation is needed to ensure sufficient extracorporeal blood flow in patients initiating ECMO. However, excessive overhydration is known to increase mortality in critically ill patients. Therefore, in order to define a tolerant volume range in patients undergoing ECMO treatment, the association between cumulative fluid balance (CFB) and outcome was evaluated in patients undergoing ECMO. METHODS: This retrospective multicenter cohort study was conducted with 723 patients who underwent ECMO in three tertiary care hospitals between 2005 and 2016. CFB was calculated as total fluid input minus total fluid output during the first 3 days from ECMO initiation. The patients were divided into groups that initiated ECMO owing to cardiovascular disease (CVD)-related or non-cardiovascular disease (non-CVD)-related causes. The primary endpoint was mortality within 90 days after ECMO commencement. RESULTS: Totals of 406 and 317 patients were included in the CVD and non-CVD groups, respectively. In the CVD group, the mean age was 58.4 ± 17.7 years, and 68.2% were male. The mean age was 55.7 ± 15.7 years, and 65.3% were male in the non-CVD group. The median CFB values were 64.7 and 53.5 ml/kg in the CVD and non-CVD groups, respectively. Multivariable analysis using Cox proportional hazards models revealed a significantly increased risk of 90-day mortality in patients with higher CFB values in both the CVD and non-CVD groups. However, the risks were elevated only in the two CFB quartile groups with the largest CFB amounts. Cubic spline models showed that mortality risk began to increase significantly when CFB was 82.3 ml/kg in the CVD group. In patients with respiratory diseases, the mortality risk increase was significant for those with CFB levels above 189.6 ml/kg. CONCLUSIONS: Mortality risk did not increase until a certain level of fluid overload was reached in patients undergoing ECMO. Adequate fluid resuscitation is critical to improving outcomes in these patients.

Association between diuretics and successful discontinuation of continuous renal replacement therapy in critically ill patients with acute kidney injury.

BACKGROUND: Despite aggressive application of continuous renal replacement therapy (CRRT) in critically ill patients with acute kidney injury (AKI), there is no consensus on diuretic therapy when discontinuation of CRRT is attempted. The effect of diuretics on discontinuation of CRRT in critically ill patients was evaluated. METHODS: This retrospective cohort study enrolled 1176 adult patients who survived for more than 3 days after discontinuing CRRT between 2009 and 2014. Patients were categorized depending on the re-initiation of renal replacement therapy within 3 days after discontinuing CRRT or use of diuretics. Changes in urine output (UO) and renal function after discontinuing CRRT were outcomes. Predictive factors for successful discontinuation of CRRT were also analyzed. RESULTS: The CRRT discontinuation group had a shorter duration of CRRT, more frequent use of diuretics after discontinuing CRRT, and greater UO on the day before CRRT discontinuation [day minus 1 (day - 1)]. The diuretics group had greater increases in UO and serum creatinine elevation after discontinuing CRRT. In the CRRT discontinuation group, continuous infusion of furosemide tended to increase UO more effectively. Multivariable regression analysis identified high day - 1 UO and use of diuretics as significant predictors of successful discontinuation of CRRT. Day - 1 UO of 125 mL/day was the cutoff value for predicting successful discontinuation of CRRT in oliguric patients treated with diuretics following CRRT. CONCLUSIONS: Day - 1 UO and aggressive diuretic therapy were associated with successful CRRT discontinuation. Diuretic therapy may be helpful when attempting CRRT discontinuation in critically ill patients with AKI, by inducing a favorable fluid balance, especially in oliguric patients.

Net ultrafiltration intensity and mortality in critically ill patients with fluid overload.

BACKGROUND: Although net ultrafiltration (UFNET) is frequently used for treatment of fluid overload in critically ill patients with acute kidney injury, the optimal intensity of UFNET is unclear. Among critically ill patients with fluid overload receiving renal replacement therapy (RRT), we examined the association between UFNET intensity and risk-adjusted 1-year mortality. METHODS: We selected patients with fluid overload ≥ 5% of body weight prior to initiation of RRT from a large academic medical center ICU dataset. UFNET intensity was calculated as the net volume of fluid ultrafiltered per day from initiation of either continuous or intermittent RRT until the end of ICU stay adjusted for patient hospital admission body weight. We stratified UFNET as low (≤ 20 ml/kg/day), moderate (> 20 to ≤ 25 ml/kg/day) or high (> 25 ml/kg/day) intensity. We adjusted for age, sex, body mass index, race, surgery, baseline estimated glomerular filtration rate, oliguria, first RRT modality, pre-RRT fluid balance, duration of RRT, time to RRT initiation from ICU admission, APACHE III score, mechanical ventilation use, suspected sepsis, mean arterial pressure on day 1 of RRT, cumulative fluid balance during RRT and cumulative vasopressor dose during RRT. We fitted logistic regression for 1-year mortality, Gray's survival model and propensity matching to account for indication bias. RESULTS: Of 1075 patients, the distribution of high, moderate and low-intensity UFNET groups was 40.4%, 15.2% and 44.2% and 1-year mortality was 59.4% vs 60.2% vs 69.7%, respectively (p = 0.003). Using logistic regression, high-intensity compared with low-intensity UFNET was associated with lower mortality (adjusted odds ratio 0.61, 95% CI 0.41-0.93, p = 0.02). Using Gray's model, high UFNET was associated with decreased mortality up to 39 days after ICU admission (adjusted hazard ratio range 0.50-0.73). After combining low and moderate-intensity UFNET groups (n = 258) and propensity matching with the high-intensity group (n = 258), UFNET intensity > 25 ml/kg/day compared with ≤ 25 ml/kg/day was associated with lower mortality (57% vs 67.8%, p = 0.01). Findings were robust to several sensitivity analyses. CONCLUSIONS: Among critically ill patients with ≥ 5% fluid overload and receiving RRT, UFNET intensity > 25 ml/kg/day compared with ≤ 20 ml/kg/day was associated with lower 1-year risk-adjusted mortality. Whether tolerating intensive UFNET is just a marker for recovery or a mediator requires further research.

Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury.

BACKGROUND: The optimal time to initiate renal replacement therapy (RRT) in intensive care unit (ICU) patients with acute kidney injury (AKI) is unclear. We examined the impact of early RRT on long-term mortality, risk of chronic kidney disease (CKD), and end-stage renal disease (ESRD). METHODS: This cohort study included all adult patients treated with continuous RRT in the ICU at Aarhus University Hospital, Skejby, Denmark (2005-2015). Data were obtained from a clinical information system and population-based registries. Early treatment was defined as RRT initiation at AKI stage 2 or below, and late treatment was defined as RRT initiation at AKI stage 3. Inverse probability of treatment (IPT) weights were computed from propensity scores. The IPT-weighted cumulative risk of CKD (estimated glomerular filtration rate < 60 ml/minute/1.73 m2), ESRD, and mortality was estimated and compared using IPT-weighted Cox regression. RESULTS: The mortality, CKD, and ESRD analyses included 1213, 303, and 617 patients, respectively. The 90-day mortality in the early RRT group was 53.6% compared with 46.0% in the late RRT group (HR 1.24, 95% CI 1.03-1.48). The 90-day to 5-year mortality was 37.7% and 41.5% in the early and late RRT groups, respectively (HR 0.95, 95% CI 0.70-1.29). The 5-year risk of CKD was 35.9% in the early RRT group and 44.9% in the late RRT group (HR 0.74, 95% CI 0.46-1.18). The 5-year risk of ESRD was 13.3% in the early RRT group and 16.7% in the late RRT group (HR 0.79, 95% CI 0.47-1.32). CONCLUSIONS: Early initiation was associated with increased 90-day mortality. In patients surviving to day 90, early initiation was not associated with a major impact on long-term mortality or risk of CKD and ESRD. Despite potential residual confounding due to the observational design, our findings do not support that early RRT initiation is superior to late initiation.

High-volume hemofiltration in adult burn patients with septic shock and acute kidney injury: a multicenter randomized controlled trial.

BACKGROUND: Sepsis and septic shock occur commonly in severe burns. Acute kidney injury (AKI) is also common and often results as a consequence of sepsis. Mortality is unacceptably high in burn patients who develop AKI requiring renal replacement therapy and is presumed to be even higher when combined with septic shock. We hypothesized that high-volume hemofiltration (HVHF) as a blood purification technique would be beneficial in this population. METHODS: We conducted a multicenter, prospective, randomized, controlled clinical trial to evaluate the impact of HVHF on the hemodynamic profile of burn patients with septic shock and AKI involving seven burn centers in the United States. Subjects randomized to the HVHF were prescribed a dose of 70 ml/kg/hour for 48 hours while control subjects were managed in standard fashion in accordance with local practices. RESULTS: During a 4-year period, a total of nine subjects were enrolled for the intervention during the ramp-in phase and 28 subjects were randomized, 14 each into the control and HVHF arms respectively. The study was terminated due to slow enrollment. Ramp-in subjects were included along with those randomized in the final analysis. Our primary endpoint, the vasopressor dependency index, decreased significantly at 48 hours compared to baseline in the HVHF group (p = 0.007) while it remained no different in the control arm. At 14 days, the multiple organ dysfunction syndrome score decreased significantly in the HVHF group when compared to the day of treatment initiation (p = 0.02). No changes in inflammatory markers were detected during the 48-hour intervention period. No significant difference in survival was detected. No differences in adverse events were noted between the groups. CONCLUSIONS: HVHF was effective in reversing shock and improving organ function in burn patients with septic shock and AKI, and appears safe. Whether reversal of shock in these patients can improve survival is yet to be determined. TRIAL REGISTRATION: Clinicaltrials.gov NCT01213914 . Registered 30 September 2010.

Therapy of acute kidney injury in the perioperative setting.

PURPOSE OF REVIEW: The current review analyzes the current pharmacologic approaches in cardiac surgery-associated acute kidney injury and renal replacement/support therapies. RECENT FINDINGS: Hemodynamic management and promising therapies, including atrial natriuretic peptide, calcium sensitizer inodilators, and mesenchymal stem cells have been discussed. Encouraging results from pre-emptive renal replacement therapies have been also addressed. SUMMARY: Cardiac surgery is responsible for the highest risk of renal dysfunction with respect to other surgical settings. A number of different and coacting insults, including toxins, renal hypoperfusion, ischemia-reperfusion injury, and systemic inflammation, are leading causes of this frequent complication. Intense research is ongoing on the treatment of established cardiac surgery-associated acute kidney injury and, in this view, a holistic approach including preoperative data, risk stratification, prevention, timely diagnosis, and aggressive intervention can limit the burdening consequences of renal dysfunction in these patients. Although no specific pharmacologic and nonpharmacologic strategy can be currently recommended outside clinical research, the prompt identification of renal dysfunction and the application of multimodal treatments are fundamental aspects. Right ventricular dysfunction and increased central venous pressure, frequently affecting cardiac surgery patients, potentially lead to congestive renal dysfunction. Hemodynamic management covers a central role in these cases.

New, goal-directed approach to renal replacement therapy improves acute kidney injury treatment after cardiac surgery.

AIM: The aim of this study was to compare the efficacies of goal-directed renal replacement therapy (GDRRT) and daily hemofiltration (DHF) for treating acute kidney injury (AKI) patients after cardiac surgery. METHODS: In our retrospective study, we included 140 cardiac surgery AKI patients who were treated with renal replacement therapy (RRT) from 2002 to 2010. Two patient groups, which comprised 70 patients who received DHF from January 2002 to September 2008 and 70 patients treated with GDRRT from October 2009 to September 2010 were pair-wise compared regarding clinical outcomes, as well as the incidence of adverse events. RESULTS: In-hospital and 30-day mortality rates were 45.7% and 41.4% in the GDRRT and 48.6% and 54.3% in the DHF group, respectively, but without statistically significant differences. GDRRT patients needed statistically significantly shorter hospital and intensive care unit (ICU) stays, less frequent RRT, and shorter RRT sessions, whereas, of 11 analyzed renal outcome parameters, 6 values, including percentage of complete renal recovery and time for complete renal recovery, were significantly superior in the GDRRT group at the time of discharge. There was no significant difference in the incidence of adverse events within the initial 72 treatment hours between the 2 groups. Hospitalization expenses were less in GDRRT group than in DHF group. CONCLUSION: The GDRRT approach is superior to DHF for improving renal outcome, as well as reducing the time and cost of RRT therapy, for cardiac surgery AKI patients.

[Kidney protection therapy in acute limb ischemia]. / Leczenie nefroprotekcyjne w ostrym niedokrwieniu konczyn dolnych.

Acute limb ischaemia is relatively frequent in the population (800:1 million, with about 1000 cases per year in Zachodniopomorskie province) and is a life-threatening condition due to significant mortality (about 15%) and a high percentage of amputation (up to 25%). Early death is mainly caused by metabolic disorders associated with reperfusion syndrome following surgical revascularisation. Muscle injury caused by rhabdomyolysis leads to acute renal failure, cardiopulmonary insufficiency and generalised inflammatory reaction. Prompt treatment according to the current recommendations, including extensive fasciotomy and intensive and early nephroprotective and renal replacement therapy, offers the only chance to reduce early mortality in patients suffering from this disease. Differences in approach to the problem of renal replacement therapy presented by nephrologists/internists and surgeons are frequent and do not improve treatment outcome. The aim of this paper is to establish a standard consensus between the approach of the vascular surgeon, nephrologist and internist to achieve the best possible treatment outcomes in patients with acute limb ischaemia.

Late presentation of patients with end-stage renal disease for renal replacement therapy--is it always avoidable?

BACKGROUND: Twenty-five to 30% of new renal replacement therapy (RRT) patients present late to renal services. The proportion in whom this is avoidable, and whether awareness of chronic kidney disease (CKD) has reduced its incidence is not known. METHODS: Adult patients starting RRT (2003-2008) in a single unit were grouped according to the time interval between first presentation to the unit and start of RRT: <90 days (late presenters); 90-364 days; ≥ 365 days. 'Late presenters' were classified as follows: acute kidney injury--patients who had acute but irreversible renal failure; 'avoidable' late referrals, if they had known pre-existing CKD and 'unavoidable' late referrals, if they had unpredictable rapid progression of their CKD or had no prior contact with health care. Mortality risk associated with late presentation was explored using multivariable Cox regression. RESULTS: Late presentation was common (24.3%) but late referrals accounted for only 7.4% and 3.9% were avoidable. The incidence of late referrals decreased from 9.2% in 2003-2005 to 5.5% in 2006-2008 (trend P = 0.07). Late presentation was associated with increased mortality after adjusting for comorbidity, transplantation and permanent vascular access, and the majority of late presenters died due to malignancy or withdrawal of RRT. CONCLUSIONS: The lower incidence of late referrals and the falling trend could be due to implementation of automated estimated glomerular filtration rate reporting and the increased awareness of CKD in primary care. Future prospective studies are needed to examine the extent to which frailty contributes to this mortality risk.