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BackgroundCorticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration.MethodsWe used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29–84 days).ResultsOf 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively).ConclusionA shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

Background: Kidney injury is a well-described adverse event of tyrosine kinase inhibitors (TKIs), thought to be mediated predominantly through glomerular damage. However, risk factors for kidney injury and the mechanism of injury are poorly defined in a wide range of cancers. Methods: This is a secondary analysis of 539 patients in the control arm of an international randomized clinical trial of patients with hepatocellular carcinoma treated with sorafenib, a vascular endothelial growth-factor receptor (VEGFR) TKI. Risk factors for developing acute kidney injury (AKI) while being treated with sorafenib were evaluated by multivariable logistic regression. We performed subgroup analyses of AKI stratified into proteinuric and non-proteinuric AKI. Results: While on study, 16% of patients developed an AKI. A decrease in systolic blood pressure was positively associated with developing any AKI (OR 1.70, 95% CI 1.03–2.82). In the subgroup analyses, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI (OR 2.15, 95% CI 1.00–4.61), but there was no association with developing a non-proteinuric AKI. Conclusions: In patients with hepatocellular carcinoma taking sorafenib, a decrease in systolic blood pressure was positively associated with developing a proteinuric AKI. However, there was no association between a decrease in blood pressure and the development of a non-proteinuric AKI. Thus, the development of AKI among patients taking VEGFR-TKIs cannot be fully explained by a hemodynamic effect. Our study highlights the need to better understand the varying mechanisms of kidney injury in patients.

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

BACKGROUND AND OBJECTIVES: Immune checkpoint inhibitor use in oncology is increasing rapidly. We sought to determine the frequency, severity, cause, and predictors of AKI in a real-world population receiving checkpoint inhibitors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We included all patients who received checkpoint inhibitor therapy from May 2011 to December 2016 at Massachusetts General Hospital. Baseline serum creatinine, averaged 6 months before checkpoint inhibitor start date, was compared with all subsequent creatinine values within 12 months of starting therapy. AKI was defined by Kidney Disease: Improving Global Outcomes criteria for fold changes in creatinine from baseline. Sustained AKI events lasted at least 3 days and was our primary outcome. The cause of sustained AKI was determined by chart review. Cumulative incidence and subdistribution hazard models were used to assess the relationship between baseline demographics, comorbidities, and medications, and sustained AKI and potential checkpoint inhibitor–related AKI. RESULTS: We included 1016 patients in the analysis. Average age was 63 (SD 13) years, 61% were men, and 91% were white. Mean baseline creatinine was 0.9 mg/dl (SD 0.4 mg/dl), and 169 (17%) had CKD (eGFR

The American Society of Nephrology recommends against routine cancer screening among asymptomatic patients receiving maintenance dialysis on the basis of limited survival benefit. To determine the frequency of colorectal cancer screening among patients on dialysis and the extent to which screening tests were targeted toward patients at lower risk of death and higher likelihood of receiving a kidney transplant, we performed a cohort study of 469,574 Medicare beneficiaries ages ≥50 years old who received dialysis between January 1, 2007 and September 30, 2012. We examined colorectal cancer screening tests according to quartiles of risk of mortality and kidney transplant on the basis of multivariable Cox modeling. Over a median follow-up of 1.5 years, 11.6% of patients received a colon cancer screening test (57.9 tests per 1000 person-years). Incidence rates of colonoscopy, flexible sigmoidoscopy, and fecal occult blood test were 27.9, 0.6, and 29.5 per 1000 person-years, respectively. Patients in the lowest quartile of mortality risk were more likely to be screened than those in the highest quartile (hazard ratio, 1.53; 95% confidence interval, 1.49 to 1.57; 65.1 versus 46.4 tests per 1000 person-years, respectively), amounting to a 33% higher rate of testing. Additionally, compared with patients least likely to receive a transplant, patients most likely to receive a transplant were more likely to be screened (hazard ratio, 1.68; 95% confidence interval, 1.64 to 1.73). Colon cancer screening is being targeted toward patients on dialysis at lowest risk of mortality and highest likelihood of transplantation, but absolute rates are high, suggesting overscreening.

Background Slow gait speed is associated with hospitalization and death. We examined whether predialysis fluid overload contributes to gait speed impairment. Methods We measured predialysis gait speed at baseline and 12 and 24 months among 298 patients recruited in the A Cohort Study to Investigate the Value of Exercise in ESRD/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESRD. We used multivariable linear mixed modeling to examine associations between patient data and gait speed. We then added either bioimpedance-estimated volume of predialysis fluid overload or volume of delivered ultrafiltration to ascertain whether fluid excess was associated with gait speed and its trajectory. We also tested whether fluid overload change with time was predictive of gait speeds. Results The mean baseline gait speed was 1.01 m/s and it declined by an average of 0.08 m/s/year. Older age, nonwhite race, Hispanic ethnicity, diabetes, recent fall, recent hospitalization, tobacco use and lower serum albumin were associated with slower gait speed. Each liter of predialysis fluid overload was associated with a 0.02 m/s slower gait speed [95% confidence interval (CI) 0.01–0.04, P = 0.008] and 0.05 m/s additional slowing per year (95% CI 0.03–0.06, P Conclusions Predialysis fluid overload was associated with slower gait speed and gait speed decline over time. Interventions that limit fluid overload may lead to improvements in physical performance.

Pretende-se com a presente pesquisa estabelecer aproximações entre teoria e prática no ensino de Língua Estrangeira (LE), especificamente Língua Espanhola (E/LE), em um curso de Educação Profissional (EP). Como objeto de investigação foi selecionado para o desenvolvimento desta pesquisa um curso técnico em agropecuária integrado ao Ensino Médio (EM) de um campus de Instituto Federal (IF), por ser atualmente o curso com maior número de alunos matriculados. Como procedimento metodológico foi empregada a pesquisa documental e a análise de conteúdo. Esta pesquisa envolveu quatro fases distintas e objetivou levantar temas que possam iluminar, posteriormente, a elaboração de planos de ensino temáticos destinados ao ensino-aprendizagem de E/LE a estudantes do 3º ano do curso técnico em agropecuária integrado ao EM, em consonância com a discussão crítica das especificidades, particularidades do E/LE no contexto da EP à formação cidadã do educando. Para tal, realizou-se o levantamento de temas categorizados pertinentes a três diferentes disciplinas técnicas (Produção Animal III, Culturas Perenes, Irrigação e Drenagem) do 3º ano do curso, constantes do Projeto Pedagógico de Curso (PPC), e das necessidades latentes dos futuros profissionais, que ingressarão no mundo do trabalho, sem a pretensão de que a ele se subordinem acriticamente. Os resultados apontam no sentido de que os temas elencados propiciam atividades de leitura e de discussão na LE, bem como a participação dos envolvidos em situações comunicativas autênticas. Espera-se que os temas propostos nesta pesquisa possam contribuir como materiais de apoio para docentes de LE na elaboração de planos de ensino temáticos, visando um ensino menos estruturalista.Palavras-chave: Ensino de Língua Espanhola. Educação Profissional Tecnológica. Plano de Ensino Temático. Ensino Médio Integrado.AbstractIt is intended with the present research to establish approximations between theory and practice in the teaching of foreign language (LE), specifically Spanish Language (E/LE), in a Professional Education (PE) course. As research object, for the development of our research a technical course was selected in agriculture integrated into the High School of a campus of the Federal Institute (IF) because it is currently the course with the highest number of enrolled students . As a methodological procedure, documentary research and content analysis were used. This research involved four distinct phases and aimed at raising themes that could later illuminate the elaboration of thematic teaching plans for E/LE teaching and learning to students of the 3rd year of the agricultural technical course integrated to High School, in line with the critical discussion of the specificities, particularities of the E/LE i the context of the PE to the learners’s citizenship education . Therefore, survey was carried out of categorized themes pertinent to three different technical subjects (Animal Production III, Perennial Cultures, Irrigation and Drainage) of the 3rd year of the course, included in the Pedagogical Course Project (PPC), and the latent needs of future professionals who will enter the labor market, without the intention that they subordinate themselves uncritically. The results point out that the topics listed provide LE reading and discussion activities, as well as the participation of those involved in authentic communicative situations. It is hoped that the themes proposed in this research can contribute as materials to support LE teachers in the elaboration of thematic teaching plans, aiming at a less structuralist teaching.Keywords: Teaching Spanish Language. Professional Technological Education. Thematic Teaching Plan. Integrated High School.