ETIENNE MARIA VASCONCELLOS DE MACEDO
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- Timing of Dialysis Initiation in Acute Kidney Injury and Acute-On-Chronic Renal Failure(2013) MACEDO, Etienne; MEHTA, Ravindra L.The decision to provide dialytic support and choosing the ideal moment to initiate therapy are common impasses for physicians treating patients with acute kidney injury (AKI). Although renal replacement therapy (RRT) has been extensively used in clinical practice for more than 30years, there is a paucity of evidence to guide clinicians on the optimal utilization of RRT in AKI. In the absence of traditional or urgent indications, there is no consensus on whether dialysis should be offered and when it should be started. The lack of agreed-upon parameters to guide the decision, the fear of the risk of the procedure, and the possible contribution to worse prognosis with RRT have resulted in a considerable variation in practice among physicians and centers. In this review, we summarize the evidence evaluating time of initiation of RRT and discuss possible approaches for future trials in addressing this issue.
- Rationale and Design of the Genetic Contribution to Drug Induced Renal Injury (DIRECT) Study(2016) AWDISHU, Linda; NIEVERGELT, Caroline M.; DAVENPORT, Andrew; MURRAY, Patrick T.; MACEDO, Etienne; CERDA, Jorge; CHAKARAVARTHI, Raj; RAO, Satish P. Ramachandra; HOLDEN, Arthur; GOLDSTEIN, Stuart L.; MEHTA, Ravindra L.Introduction: Nephrotoxicity from drugs accounts for 18% to 27% of cases of acute kidney injury. Determining a genetic predisposition maypotentially be important in minimizing risk. The aims of this study are as follows: to determine whether a genetic predisposition exists for the development of drug-induced kidney disease (DIKD), using genome-wide association and whole-genome sequencing studies; to describe the frequency, course, risk factors, resolution and outcomes of DIKD cases; to investigate the role of ethnic/racial variability in the genetics of DIKD; and to explore the use of different tools establishing causality of DIKD. Methods: A total of 800 patients will be enrolled worldwide and blood samples for DNA collected. Data on the patient risk factors, vital signs, laboratory parameters, drug exposure, and DIKD course will be recorded. A panel of nephrologists will adjudicate all cases. Genome-wide association studies will be conducted using population controlsmatched on biogeographic ancestry to determine whether there is agenetic predisposition to DIKD. The primary endpoint is the identification of specific drug-related polymorphisms associated with DIKD. Secondary endpoints include the following: frequency of DIKD by causal drug and drug combinations; DIKD genetic variability; exploration of causality assessment tools; risk factor identification; description of the course of DIKD, including mortality and dialysis dependency at hospital discharge and 28 and 90 days post-event. Results: Data are currently being analyzed. Results are pending. Discussion: The Genetic Contribution to Drug Induced Renal Injury (DIRECT) study will be the first observational cohort study to investigate the genetic determinants of DIKD. If the trial is positive, its findings will potentially translate into safer patient outcomes, by genotypic individualization of therapy and minimization of harm.
- Targeting Recovery from Acute Kidney Injury: Incidence and Prevalence of Recovery(2014) MACEDO, Etienne; MEHTA, Ravindra L.Since the creation of Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Renal Disease (RIFLE) criteria in the last 10 years, the use of a standardized definition of acute kidney injury (AKI) has made it possible for epidemiologic studies to document the increasing incidence of AKI, especially in the critical care setting [1]. In addition, several studies applying the criteria of RIFLE, Acute Kidney Injury Network, and, more recently, the Kidney Disease: Improving Global Outcome, were able to establish the association of severity of AKI with adverse clinical outcomes, including the development of chronic kidney disease (CKD) and end-stage renal disease (ESRD) [2-4]. Although, until recently, it was thought that survivors from an AKI episode frequently recover kidney function, cumulative observational data over the past decade have confirmed the association of AKI with the increased risk for permanent kidney damage, with subsequent development of CKD [5]. The epidemiological studies that we will present and discuss in this review confirm and clarify the association of AKI with the development of CKD and ESRD [6-8]. (C) 2014 S. Karger AG, Basel
- Phenotype standardization for drug-induced kidney disease(2015) MEHTA, Ravindra L.; AWDISHU, Linda; DAVENPORT, Andrew; MURRAY, Patrick T.; MACEDO, Etienne; CERDA, Jorge; CHAKARAVARTHI, Raj; HOLDEN, Arthur L.; GOLDSTEIN, Stuart L.Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition.
- Clinical Approach to the Diagnosis of Acute Kidney Injury(2014) MACEDO, Etienne Maria Vasconcellos de; MEHTA, Ravindra L.
- Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study(2016) MEHTA, Ravindra L.; BURDMANN, Emmanuel A.; CERDA, Jorge; FEEHALLY, John; FINKELSTEIN, Fredric; GARCIA-GARCIA, Guillermo; GODIN, Melanie; JHA, Vivekanand; LAMEIRE, Norbert H.; LEVIN, Nathan W.; LEWINGTON, Andrew; LOMBARDI, Raul; MACEDO, Etienne; ROCCO, Michael; ARONOFF-SPENCER, Eliah; TONELLI, Marcello; ZHANG, Jing; REMUZZI, GiuseppeBackground Epidemiological data for acute kidney injury are scarce, especially in low-income countries (LICs) and lower-middle-income countries (LMICs). We aimed to assess regional differences in acute kidney injury recognition, management, and outcomes. Methods In this multinational cross-sectional study, 322 physicians from 289 centres in 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidney injury in hospital and non-hospital settings who met criteria for acute kidney injury. Signs and symptoms at presentation, comorbidities, risk factors for acute kidney injury, and process-of-care data were obtained at the start of acute kidney injury, and need for dialysis, renal recovery, and mortality recorded at 7 days, and at hospital discharge or death, whichever came earlier. We classified countries into high-income countries (HICs), upper-middle-income countries (UMICs), and combined LICs and LMICs (LLMICs) according to their 2014 gross national income per person. Findings Between Sept 29 and Dec 7, 2014, data were collected from 4018 patients. 2337 (58%) patients developed community-acquired acute kidney injury, with 889 (80%) of 1118 patients in LLMICs, 815 (51%) of 1594 in UMICs, and 663 (51%) of 1241 in HICs (for HICs vs UMICs p = 0.33; p < 0.0001 for all other comparisons). Hypotension (1615 [40%] patients) and dehydration (1536 [38%] patients) were the most common causes of acute kidney injury. Dehydration was the most frequent cause of acute kidney injury in LLMICs (526 [46%] of 1153 vs 518 [32%] of 1605 in UMICs vs 492 [39%] of 1260 in HICs) and hypotension in HICs (564 [45%] of 1260 vs 611 [38%%] of 1605 in UMICs vs 440 [38%] of 1153 LLMICs). Mortality at 7 days was 423 (11%) of 3855, and was higher in LLMICs (129 [12%] of 1076) than in HICs (125 [10%] of 1230) and UMICs (169 [11%] of 1549). Interpretation We identified common aetiological factors across all countries, which might be amenable to a standardised approach for early recognition and treatment of acute kidney injury. Study limitations include a small number of patients from outpatient settings and LICs, potentially under-representing the true burden of acute kidney injury in these areas. Additional strategies are needed to raise awareness of acute kidney injury in community healthcare settings, especially in LICs.
- Renal Recovery after Acute Kidney Injury(2016) MACEDO, Etienne; MEHTA, Ravindra L.Until recently, patients surviving an episode of acute kidney injury (AKI) were assumed to have a good renal prognosis. This belief was predominantly based on studies that used heterogeneous AKI definitions and that considered renal recovery as dialysis independence at hospital discharge. Since standardized definitions of AKI have become available, several studies have established an association between AKI and adverse clinical outcomes. It is now well recognized that while the glomerular filtration rate generally improves after AKI, the renal recovery process is often incomplete and can result in a chronic decrease in kidney function. The loss of kidney function can vary from subclinical decreases in the glomerular filtration rate to end-stage renal disease. In this chapter, we review our current understanding of renal recovery following AKI and discuss the main studies that have established associations between AKI and the development of chronic kidney disease and end-stage renal disease [1]. (C) 2016 S. Karger AG, Basel
- Continuous Dialysis Therapies: Core Curriculum 2016(2016) MACEDO, Etienne; MEHTA, Ravindra L.
- Effluent volume and dialysis dose in CRRT: time for reappraisal(2012) MACEDO, Etienne; GRANADO, Rolando Claure-Del; MEHTA, Ravindra L.The results of several studies assessing dialysis dose have dampened the enthusiasm of clinicians for considering dialysis dose as a modifiable factor influencing outcomes in patients with acute kidney injury. Powerful evidence from two large, multicenter trials indicates that increasing the dialysis dose, measured as hourly effluent volume, has no benefit in continuous renal replacement therapy (CRRT). However, some important operational characteristics that affect delivered dose were not evaluated. Effluent volume does not correspond to the actual delivered dose, as a decline in filter efficacy reduces solute removal during therapy. We believe that providing accurate parameters of delivered dose could improve the delivery of a prescribed dose and refine the assessment of the effect of dose on outcomes in critically ill patients treated with CRRT.
- Biomarkers for acute kidney injury: combining the new silver with the old gold(2013) MACEDO, Etienne; MEHTA, Ravindra L.