Acute kidney injury: an increasing global concern Lameire, Norbert H, Prof; Bagga, Arvind, Prof; Cruz, Dinna, MD ...
The Lancet (British edition),
07/2013, Letnik:
382, Številka:
9887
Journal Article
Recenzirano
Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic ...options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.
In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group ...of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.
Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition ...and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 (TIMP-2 × IGFBP7) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.
Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal ...replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO ...guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI; however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.
AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year ...after discharge.
We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records.
Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio aHR, 1.18; 95% confidence interval 95% CI, 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12).
AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge.
INTRODUCTIONAcute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term ...progression to kidney failure is required.METHODSWe enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression.RESULTSHigher MCP-1 and YKL-40 levels were associated with greater eGFR decline and increased incidence of the composite renal outcome, whereas higher UMOD levels were associated with smaller eGFR declines and decreased incidence of the composite kidney outcome. A multimarker score increased prognostic accuracy and reclassification compared with traditional clinical variables alone. The mouse model of renal atrophy showed greater Ccl2 and Chi3l1 mRNA expression in infiltrating macrophages and neutrophils, respectively, and evidence of progressive renal fibrosis compared with the repair model. The repair model showed greater Umod expression in the loop of Henle and correspondingly less fibrosis.CONCLUSIONSBiomarker levels at 3 months after hospitalization identify patients at risk for kidney disease progression.FUNDINGNIH.
No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in ...the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.
The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight PBW), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.
No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.
A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.
The National Heart, Lung, and Blood Institute.
Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general ...epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.
Purpose
To review the mechanisms of action, expected efficacy and side effects of strategies to control hyperkalemia in acutely ill patients.
Methods
We searched MEDLINE and EMBASE for relevant ...papers published in English between Jan 1, 1938, and July 1, 2018, in accordance with the PRISMA Statement using the following terms: “hyperkalemia,” “intensive care,” “acute kidney injury,” “acute kidney failure,” “hyperkalemia treatment,” “renal replacement therapy,” “dialysis,” “sodium bicarbonate,” “emergency,” “acute.” Reports from within the past 10 years were selected preferentially, together with highly relevant older publications.
Results
Hyperkalemia is a potentially life-threatening electrolyte abnormality and may cause cardiac electrophysiological disturbances in the acutely ill patient. Frequently used therapies for hyperkalemia may, however, also be associated with morbidity. Therapeutics may include the simultaneous administration of insulin and glucose (associated with frequent dysglycemic complications), β-2 agonists (associated with potential cardiac ischemia and arrhythmias), hypertonic sodium bicarbonate infusion in the acidotic patient (representing a large hypertonic sodium load) and renal replacement therapy (effective but invasive). Potassium-lowering drugs can cause rapid decrease in serum potassium level leading to cardiac hyperexcitability and rhythm disorders.
Conclusions
Treatment of hyperkalemia should not only focus on the ability of specific therapies to lower serum potassium level but also on their potential side effects. Tailoring treatment to the patient condition and situation may limit the risks.
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