The Experts below are selected from a list of 234 Experts worldwide ranked by ideXlab platform
Scott M. Sutherland - One of the best experts on this subject based on the ideXlab platform.
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Nephrotoxins and nephrotoxic acute kidney injury
Pediatric Nephrology, 2019Co-Authors: Amanda M Uber, Scott M. SutherlandAbstract:Although the concept of nephrotoxicity has been recognized for more than 80 years, interest in Nephrotoxins has intensified dramatically over the past two decades. Much of this attention has rightfully been focused on pharmaceutical agents and iatrogenic harm; however, it is important for providers to recognize that Nephrotoxins can be found in naturally occurring substances as well. Although Nephrotoxins exist in a myriad of forms, the means by which they induce injury can be organized into a few categories. For most of these agents, regardless of the mechanism, the final common pathway is acute kidney injury (AKI). Unfortunately, therapeutic options are limited and no treatments currently exist to reverse nephrotoxic AKI once it occurs. As a result, current strategies focus on increased awareness, Nephrotoxin avoidance, early injury detection, and mitigation of disease severity. The goal of this review is to summarize our current understanding of nephrotoxic mechanisms and the epidemiology of nephrotoxic AKI. Additionally, avoidance and preventative strategies are discussed, screening approaches are suggested, and chronic monitoring recommendations are made.
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electronic health record enabled big data approaches to Nephrotoxin associated acute kidney injury risk prediction
Pharmacotherapy, 2018Co-Authors: Scott M. SutherlandAbstract:Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to Nephrotoxins accounts for 15-25% of AKI cases. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling.
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Electronic Health Record–Enabled Big‐Data Approaches to Nephrotoxin‐Associated Acute Kidney Injury Risk Prediction
Pharmacotherapy, 2018Co-Authors: Scott M. SutherlandAbstract:Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to Nephrotoxins accounts for 15-25% of AKI cases. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling.
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Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery.
Pediatric nephrology (Berlin Germany), 2018Co-Authors: Amanda M Uber, Maria E. Montez-rath, David M. Kwiatkowski, Catherine D. Krawczeski, Scott M. SutherlandAbstract:Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of Nephrotoxins. This study examines the epidemiology of Nephrotoxin exposure and Nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS). This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high Nephrotoxin exposure was defined as receipt of ≥ 3 Nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥ 2. Poisson models were used to compute adjusted relative risk (aRR) of high Nephrotoxin exposure for AKI. One hundred fifty-four children (median age 20.4 months, IQR 2.3–59.5) were included. One hundred thirty-one (85.1%) received at least one Nephrotoxin; 32 (20.8%) received ≥ 3 Nephrotoxins. The most commonly administered medications were ketorolac (n = 74, 48.1%), aspirin (n = 62, 40.3%), ibuprofen (n = 51, 33.1%), vancomycin (n = 39, 25.3%), piperacillin/tazobactam (n = 35, 22.7%), and enalapril (n = 14, 9.1%). AKI occurred more commonly in those exposed to ≥ 3 Nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR = 1.2, 95% CI 0.9–1.7). Severe AKI was similar between those with and without high Nephrotoxin exposure (21.9 vs. 19.7%, p = 0.78). Nephrotoxin use is common following pediatric CHS. While we found no association between high Nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common Nephrotoxins, less injurious agents exist and Nephrotoxin exposure may represent a modifiable risk factor for AKI.
Brenda R. C. Kurnik - One of the best experts on this subject based on the ideXlab platform.
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Cause of acute tubular necrosis affects its prognosis. The Auriculin Anaritide Acute Renal Failure Study Group.
JAMA Internal Medicine, 1997Co-Authors: Lawrence S Weisberg, F. C. Genter, Robin L. Allgren, Brenda R. C. KurnikAbstract:Background: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. Objective: To test the hypothesis that the cause of ATN affects its clinical outcome. Methods: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. Results: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysisfree survival improved significantly and mortality tended to decline with advancing age. Conclusions: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious comorbidities in the ischemic ATN group. Advancing age was associated with improved dialysisfree survival and a tendency toward reduced mortality in patients with ischemic ATN. Arch Intern Med. 1997;157:1833-1838
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cause of acute tubular necrosis affects its prognosis
JAMA Internal Medicine, 1997Co-Authors: Lawrence S Weisberg, F. C. Genter, Robin L. Allgren, Brenda R. C. KurnikAbstract:Background: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. Objective: To test the hypothesis that the cause of ATN affects its clinical outcome. Methods: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. Results: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysisfree survival improved significantly and mortality tended to decline with advancing age. Conclusions: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious comorbidities in the ischemic ATN group. Advancing age was associated with improved dialysisfree survival and a tendency toward reduced mortality in patients with ischemic ATN. Arch Intern Med. 1997;157:1833-1838
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cause of acute tubular necrosis affects its prognosis the auriculin anaritide acute renal failure study group
JAMA Internal Medicine, 1997Co-Authors: Lawrence S Weisberg, F. C. Genter, Robin L. Allgren, Brenda R. C. KurnikAbstract:BACKGROUND: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. OBJECTIVE: To test the hypothesis that the cause of ATN affects its clinical outcome. METHODS: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. RESULTS: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysis-free survival improved significantly and mortality tended to decline with advancing age. CONCLUSIONS: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious commorbidities in the ischemic ATN group. Advancing age was associated with improved dialysis-free survival and a tendency toward reduced mortality in patients with ischemic ATN.
Sandra L. Kane-gill - One of the best experts on this subject based on the ideXlab platform.
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Drug‐Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database
Pharmacotherapy, 2018Co-Authors: Hanna K Welch, John A Kellum, Sandra L. Kane-gillAbstract:Study objective Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Design Retrospective pharmacovigilance disproportionality analysis. Data source Food and Drug Administration Adverse Event Reporting System database. Measurements and main results We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential Nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known Nephrotoxins, 18.6% were possible Nephrotoxins, and 64.8% were new potential Nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each Nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known Nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible Nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential Nephrotoxins. Conclusion Acute kidney injury was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized as nephrotoxic according to our classification system. This report provides data on medications needing further research to determine the risk of AKI with these new potential Nephrotoxins.
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Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury
Drug Safety, 2017Co-Authors: Sandra L. Kane-gill, John A Kellum, Pamela L. Smithburger, Kianoush Kashani, Erin FrazeeAbstract:Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N -acetyl-β- d -glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N -acetyl-β- d -glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.
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Drug-associated acute kidney injury: who's at risk?
Pediatric nephrology (Berlin Germany), 2016Co-Authors: Emily L Joyce, Sandra L. Kane-gill, Dana Y. Fuhrman, John A KellumAbstract:The contribution of nephrotoxic medications to the development of acute kidney injury (AKI) is becoming better understood concomitant with the increased incidence of AKI in children. Treatment of AKI is not yet available, so prevention continues to be the most effective approach. There is an opportunity to mitigate severity and prevent the occurrence of AKI if children at increased risk are identified early and Nephrotoxins are used judiciously. Early detection of AKI is limited by the dependence of nephrologists on serum creatinine as an indicator. Promising new biomarkers may offer early detection of AKI prior to the rise in serum creatinine. Early detection of evolving AKI is improving and offers opportunities for better management of Nephrotoxins. However, the identification of patients at increased risk will remain an important first step, with a focus on the use of biomarker testing and interpretation of the results.
Lawrence S Weisberg - One of the best experts on this subject based on the ideXlab platform.
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Cause of acute tubular necrosis affects its prognosis. The Auriculin Anaritide Acute Renal Failure Study Group.
JAMA Internal Medicine, 1997Co-Authors: Lawrence S Weisberg, F. C. Genter, Robin L. Allgren, Brenda R. C. KurnikAbstract:Background: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. Objective: To test the hypothesis that the cause of ATN affects its clinical outcome. Methods: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. Results: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysisfree survival improved significantly and mortality tended to decline with advancing age. Conclusions: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious comorbidities in the ischemic ATN group. Advancing age was associated with improved dialysisfree survival and a tendency toward reduced mortality in patients with ischemic ATN. Arch Intern Med. 1997;157:1833-1838
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cause of acute tubular necrosis affects its prognosis
JAMA Internal Medicine, 1997Co-Authors: Lawrence S Weisberg, F. C. Genter, Robin L. Allgren, Brenda R. C. KurnikAbstract:Background: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. Objective: To test the hypothesis that the cause of ATN affects its clinical outcome. Methods: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. Results: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysisfree survival improved significantly and mortality tended to decline with advancing age. Conclusions: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious comorbidities in the ischemic ATN group. Advancing age was associated with improved dialysisfree survival and a tendency toward reduced mortality in patients with ischemic ATN. Arch Intern Med. 1997;157:1833-1838
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cause of acute tubular necrosis affects its prognosis the auriculin anaritide acute renal failure study group
JAMA Internal Medicine, 1997Co-Authors: Lawrence S Weisberg, F. C. Genter, Robin L. Allgren, Brenda R. C. KurnikAbstract:BACKGROUND: Acute tubular necrosis (ATN) is the most common type of acute renal failure in hospitalized patients and is associated with a high morbidity and mortality. The cause of ATN can be divided into nephrotoxic, ischemic, or mixed. OBJECTIVE: To test the hypothesis that the cause of ATN affects its clinical outcome. METHODS: The study compares clinical outcomes of patients enrolled in the placebo arm of a multicenter, randomized, double-blinded, placebo-controlled trial of anaritide (Auriculin, synthetic atrial natriuretic peptide, Scios, Mountain View, Calif) in patients with well-defined ATN. Patients were divided prospectively into groups according to the cause of ATN: pure nephrotoxic, pure ischemic, or mixed nephrotoxic and ischemic. Outcomes of interest were dialysis-free survival and all-cause mortality on day 14 and day 21. The causal groups were compared with respect to the prevalence of several comorbidities suspected of affecting the clinical outcomes. RESULTS: Mortality was 10% in the nephrotoxic group and 30% in the ischemic group on day 21. Dialysis-free survival was 66% in the nephrotoxic group and 41% in the ischemic group on day 21. Outcomes in the mixed and ischemic groups were similar. Compared with the nephrotoxic group, there was a significantly higher prevalence of cardiogenic shock, hypotension, sepsis, and respiratory failure and a tendency toward a higher prevalence of acute hepatic dysfunction in the ischemic group. Diabetes mellitus was more prevalent in the nephrotoxic group. Among patients with ischemic ATN, dialysis-free survival improved significantly and mortality tended to decline with advancing age. CONCLUSIONS: Among patients with ATN, those in whom renal ischemia was causative had significantly higher mortality and lower dialysis-free survival than those whose ATN was purely nephrotoxic in origin. This difference in clinical outcomes was associated with a higher prevalence of serious commorbidities in the ischemic ATN group. Advancing age was associated with improved dialysis-free survival and a tendency toward reduced mortality in patients with ischemic ATN.
John A Kellum - One of the best experts on this subject based on the ideXlab platform.
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drug associated acute kidney injury identified in the united states food and drug administration adverse event reporting system database
Pharmacotherapy, 2018Co-Authors: Hanna K Welch, John A Kellum, Sandra L KanegillAbstract:Study objective Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Design Retrospective pharmacovigilance disproportionality analysis. Data source Food and Drug Administration Adverse Event Reporting System database. Measurements and main results We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential Nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known Nephrotoxins, 18.6% were possible Nephrotoxins, and 64.8% were new potential Nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each Nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known Nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible Nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential Nephrotoxins. Conclusion Acute kidney injury was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized as nephrotoxic according to our classification system. This report provides data on medications needing further research to determine the risk of AKI with these new potential Nephrotoxins.
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Drug‐Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database
Pharmacotherapy, 2018Co-Authors: Hanna K Welch, John A Kellum, Sandra L. Kane-gillAbstract:Study objective Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Design Retrospective pharmacovigilance disproportionality analysis. Data source Food and Drug Administration Adverse Event Reporting System database. Measurements and main results We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential Nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known Nephrotoxins, 18.6% were possible Nephrotoxins, and 64.8% were new potential Nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each Nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known Nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible Nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential Nephrotoxins. Conclusion Acute kidney injury was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized as nephrotoxic according to our classification system. This report provides data on medications needing further research to determine the risk of AKI with these new potential Nephrotoxins.
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Clinical Relevance and Predictive Value of Damage Biomarkers of Drug-Induced Kidney Injury
Drug Safety, 2017Co-Authors: Sandra L. Kane-gill, John A Kellum, Pamela L. Smithburger, Kianoush Kashani, Erin FrazeeAbstract:Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury. Such biomarkers may have a role both for detection of drug-induced kidney disease and implementation of preventative and therapeutic strategies designed to mitigate injury. In this article, basic principles of renal biomarker use in practice are summarized, and the existing evidence for six markers specifically used to detect drug-induced kidney injury are outlined, including liver-type fatty acid binding protein, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 times insulin-like growth factor-binding protein 7 ([TIMP-2]·[IGFBP7]), kidney injury molecule-1 and N -acetyl-β- d -glucosaminidase. The results of the literature search for these six kidney damage biomarkers identified 29 unique articles with none detected for liver-type fatty acid binding protein and [TIMP-2]·[IGFBP7]. For three biomarkers, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin and N -acetyl-β- d -glucosaminidase, the majority of the studies suggest utility in clinical practice. While many questions need to be answered to clearly articulate the use of biomarkers to predict drug-induced kidney disease, current data are promising.
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Drug-associated acute kidney injury: who's at risk?
Pediatric nephrology (Berlin Germany), 2016Co-Authors: Emily L Joyce, Sandra L. Kane-gill, Dana Y. Fuhrman, John A KellumAbstract:The contribution of nephrotoxic medications to the development of acute kidney injury (AKI) is becoming better understood concomitant with the increased incidence of AKI in children. Treatment of AKI is not yet available, so prevention continues to be the most effective approach. There is an opportunity to mitigate severity and prevent the occurrence of AKI if children at increased risk are identified early and Nephrotoxins are used judiciously. Early detection of AKI is limited by the dependence of nephrologists on serum creatinine as an indicator. Promising new biomarkers may offer early detection of AKI prior to the rise in serum creatinine. Early detection of evolving AKI is improving and offers opportunities for better management of Nephrotoxins. However, the identification of patients at increased risk will remain an important first step, with a focus on the use of biomarker testing and interpretation of the results.
