Combination of biomarker with clinical risk factors for prediction of severe acute kidney injury in critically ill patients

Abstract Background Acute kidney injury (AKI) occurs commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, the effective use of disease biomarkers is indispensable from an appropriate clinical context. We conducted a retrospective cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors, so as to provide feasible information for AKI prediction. Methods All patients who were admitted in the ICU (from June 2016 to July 2017) participated in the study. The primary outcome was the detection of severe AKI within the first 7 days after patients being admitted to the ICU. The predictors were separated into three categories: chronic risk factors, acute risk factors and biochemical indicators. Results The study included 577 patients. 96 patients developed to severe AKI (16.6%) within 7 days. In addition to NephroCheck (+) (OR = 2.139, 95% CI (1.260–3.630), P = 0.005), age > 65 years (OR = 1.961, 95% CI (1.153–3.336), P = 0.013), CKD (OR = 2.573, 95% CI (1.319–5.018), P = 0.006) and PCT (+)(OR = 3.223, 95% CI (1.643–6.321), P = 0.001) were also the independent predictors of severe AKI within 7 days. Compared to NephroCheck (+) only (AUC = 0.66, 95% CI:0.60–0.72), the combination of NephroCheck (+) and risk factors (age > 65 years, CKD and PCT positive) (AUC = 0.75, 95% CI:0.70–0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within 7 days. Conclusions Although NephroCheck is an effective screening tool for recognizing high-risk patients, we found that combination with biomarker and risk factors (age > 65 years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance to patients with uncertain disease trajectories.

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Combination of biomarker with clinical risk factors for prediction of severe acute kidney injury in critically ill patients

10.21203/rs.3.rs-39774/v3 ◽

2020 ◽

Author(s):

LAN JIA ◽

Xiaohua Sheng ◽

Anna Zamperetti ◽

Yun Xie ◽

Valentina Corradi ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Tissue Inhibitor Of Metalloproteinase ◽

Disease Biomarkers ◽

Area Under Roc Curve ◽

Risk Patients ◽

Novel Biomarkers ◽

Effective Use ◽

Chronic Risk

Abstract Background: Acute kidney injury (AKI) occurs commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, the effective use of disease biomarkers is indispensable from an appropriate clinical context. We conducted a retrospective cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors, so as to provide feasible information for AKI prediction.Methods: All patients who were admitted in the ICU ( from June 2016 to July 2017) participated in the study. The primary outcome was the detection of severe AKI within the first seven days after patients being admitted to the ICU. The predictors were separated into three categories: chronic risk factors, acute risk factors and biochemical indicators. Results: The study included 577 patients. 96 patients developed to severe AKI (16.6%) within seven days. In addition to NephroCheck (+) (OR=2.139, 95% CI (1.260-3.630), P =0.005), age >65 years (OR=1.961, 95% CI (1.153-3.336), P=0.013), CKD (OR=2.573, 95% CI (1.319-5.018), P=0.006) and PCT (+)(OR=3.223, 95% CI (1.643-6.321), P=0.001) were also the independent predictors of severe AKI within seven days. Compared to NephroCheck (+) only (AUC=0.66, 95% CI:0.60-0.72), the combination of NephroCheck (+) and risk factors (age>65years, CKD and PCT positive) (AUC=0.75, 95% CI:0.70-0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within seven days.Conclusions: Although NephroCheck is an effective screening tool for recognizing high-risk patients, we found that combination with biomarker and risk factors (age>65years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance to patients with uncertain disease trajectories.

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Combination of Biomarker with Clinical Risk Factors for Prediction of Severe Acute Kidney Injury in Critically ill Patients

10.21203/rs.3.rs-39774/v1 ◽

2020 ◽

Author(s):

Lan Jia ◽

Xiaohua Sheng ◽

Anna Zamperetti ◽

Yun Xie ◽

Valentina Corradi ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Primary Outcome ◽

Screening Tool ◽

Kidney Injury ◽

Tissue Inhibitor Of Metalloproteinase ◽

Disease Biomarkers ◽

Area Under Roc Curve ◽

Novel Biomarkers ◽

Chronic Risk

Abstract Background: Acute kidney injury (AKI) occur commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, disease biomarkers require appropriate clinical context to be used effectively. We conducted a cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors would provide feasible information for AKI prediction.Methods: All patients who admitted in the ICU (June 2016 to July 2017) participated in the study. The primary outcome was severe AKI within the first 7 days of the ICU. The predictors were separated into 3 categories: chronic risk factors, acute risk factors and biochemical indicators. Results: The study included 577 patients. 96 patients developed to severe AKI (16.6%) within 7 days. In addition to NephroCheck (+) (OR=2.139, 95% CI (1.260-3.630), P =0.005), age >65 years (OR=1.961, 95% CI (1.153-3.336), P=0.013), CKD (OR=2.573, 95% CI (1.319-5.018), P=0.006) and PCT (+)(OR=3.223, 95% CI (1.643-6.321), P=0.001) were also the independent predictor of severe AKI within 7 days. Compared to NephroCheck (+) only (AUC=0.66, 95% CI:0.60-0.72), the combination of NephroCheck (+) and risk factors (age>65years, CKD and PCT positive) (AUC=0.75, 95% CI:0.70-0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within 7 days.Conclusions: Although NephroCheck is an effective screening tool for recognizing patients at high risk, we found that combination with biomarker and risk factors (age>65years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance for patients with uncertain disease trajectories.

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Combination of biomarker with clinical risk factors for prediction of severe acute kidney injury in critically ill patients

10.21203/rs.3.rs-39774/v2 ◽

2020 ◽

Author(s):

LAN JIA ◽

Xiaohua Sheng ◽

Anna Zamperetti ◽

Yun Xie ◽

Valentina Corradi ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Primary Outcome ◽

Screening Tool ◽

Kidney Injury ◽

Tissue Inhibitor Of Metalloproteinase ◽

Disease Biomarkers ◽

Area Under Roc Curve ◽

Novel Biomarkers ◽

Chronic Risk

Abstract Background: Acute kidney injury (AKI) occur commonly in the intensive care unit (ICU). Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2), known as [TIMP-2] x [IGFBP7] (NephroCheck), have been identified as novel biomarkers for the prediction of AKI risk. However, disease biomarkers require appropriate clinical context to be used effectively. We conducted a retrospective cohort study to find risk factors and assess the performance of the combination of NephroCheck with risk factors would provide feasible information for AKI prediction.Methods: All patients who admitted in the ICU (June 2016 to July 2017) participated in the study. The primary outcome was severe AKI within the first 7 days of the ICU. The predictors were separated into 3 categories: chronic risk factors, acute risk factors and biochemical indicators. Results: The study included 577 patients. 96 patients developed to severe AKI (16.6%) within 7 days. In addition to NephroCheck (+) (OR=2.139, 95% CI (1.260-3.630), P =0.005), age >65 years (OR=1.961, 95% CI (1.153-3.336), P=0.013), CKD (OR=2.573, 95% CI (1.319-5.018), P=0.006) and PCT (+)(OR=3.223, 95% CI (1.643-6.321), P=0.001) were also the independent predictor of severe AKI within 7 days. Compared to NephroCheck (+) only (AUC=0.66, 95% CI:0.60-0.72), the combination of NephroCheck (+) and risk factors (age>65years, CKD and PCT positive) (AUC=0.75, 95% CI:0.70-0.81) led to a significant increase in the area under ROC curve for severe AKI prediction within 7 days.Conclusions: Although NephroCheck is an effective screening tool for recognizing patients at high risk, we found that combination with biomarker and risk factors (age>65years, CKD, procalcitonin positive) for risk assessment of AKI has the greatest significance for patients with uncertain disease trajectories.

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Acute Kidney Injury after Cardiac Surgery: Risk Factors and Novel Biomarkers

Brazilian Journal of Cardiovascular Surgery ◽

10.21470/1678-9741-2018-0212 ◽

2019 ◽

Vol 34 (3) ◽

Cited By ~ 1

Author(s):

Shi-Min Yuan

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Kidney Injury ◽

Novel Biomarkers

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Risk factors for acute kidney injury and mortality in high risk patients undergoing cardiac surgery

PLoS ONE ◽

10.1371/journal.pone.0252209 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0252209

Author(s):

Giuseppe Filiberto Serraino ◽

Michele Provenzano ◽

Federica Jiritano ◽

Ashour Michael ◽

Nicola Ielapi ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Logistic Regression ◽

Regression Analysis ◽

Cardiac Surgery ◽

Blood Glucose ◽

Kidney Injury ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Risk Patients

Background Acute Kidney Injury (AKI) represents a clinical condition with poor prognosis. The incidence of AKI in hospitalized patients was about 22–57%. Patients undergoing cardiac surgery (CS) are particularly exposed to AKI because of the related oxidative stress, inflammation and ischemia-reperfusion damage. Hence, the risk profile of patients undergoing CS who develop AKI and who are consequently at increased mortality risk deserves further investigation. Methods We designed a retrospective study examining consecutive patients undergoing any type of open-heart surgery from January to December 2018. Patients with a history of AKI were excluded. AKI was diagnosed according to KDIGO criteria. Univariate associations between clinical variables and AKI were tested using logistic regression analysis. Variable thresholds maximizing the association with AKI were measured with the Youden index. Multivariable logistic regression analysis was performed to assess predictors of AKI through backward selection. Mortality risk factors were assessed through the Cox proportional hazard model. Results We studied 158 patients (mean age 51.2±9.7 years) of which 74.7% were males. Types of procedures performed were: isolated coronary artery bypass (CABG, 50.6%), valve (28.5%), aortic (3.2%) and combined (17.7%) surgery. Overall, incidence of AKI was 34.2%. At multivariable analysis, young age (p = 0.016), low blood glucose levels (p = 0.028), estimated Glomerular Filtration Rate (p = 0.007), pH (p = 0.008), type of intervention (p = 0.031), prolonged extracorporeal circulation (ECC, p = 0.028) and cross-clamp (p = 0.021) times were associated with AKI. The threshold for detecting AKI were 91 and 51 minutes for ECC and cross-clamp times, respectively. At survival analysis, the presence of AKI, prolonged ECC and cross-clamp times, and low blood glucose levels forecasted mortality. Conclusions AKI is common among CS patients and associates with shortened life-expectancy. Several pre-operative and intra-operative predictors are associated with AKI and future mortality. Future studies, aiming at improving prognosis in high-risk patients, by a stricter control of these factors, are awaited.

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Epidemiology of Acute Kidney Injury among Patients Receiving Concomitant Vancomycin and Piperacillin-Tazobactam: Opportunities for Antimicrobial Stewardship

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.03011-15 ◽

2016 ◽

Vol 60 (6) ◽

pp. 3743-3750 ◽

Cited By ~ 36

Author(s):

Shigehiko Karino ◽

Keith S. Kaye ◽

Bhagyashri Navalkele ◽

Bakht Nishan ◽

Madiha Salim ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Combination Therapy ◽

Kidney Injury ◽

Primary Objective ◽

Loading Dose ◽

Case Control Studies ◽

Risk Patients ◽

The Impact ◽

Extended Infusion

Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy.

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Prediction and Prevention of Acute Kidney Injury after Cardiac Surgery

BioMed Research International ◽

10.1155/2016/2985148 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 14

Author(s):

Su Rin Shin ◽

Won Ho Kim ◽

Dong Joon Kim ◽

Il-Woo Shin ◽

Ju-Tae Sohn

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Preventive Intervention ◽

Kidney Injury ◽

Risk Scores ◽

Preventive Strategy ◽

Prediction And Prevention ◽

Novel Biomarkers ◽

Almost All

The incidence of acute kidney injury after cardiac surgery (CS-AKI) ranges from 33% to 94% and is associated with a high incidence of morbidity and mortality. The etiology is suggested to be multifactorial and related to almost all aspects of perioperative management. Numerous studies have reported the risk factors and risk scores and novel biomarkers of AKI have been investigated to facilitate the subclinical diagnosis of AKI. Based on the known independent risk factors, many preventive interventions to reduce the risk of CS-AKI have been tested. However, any single preventive intervention did not show a definite and persistent benefit to reduce the incidence of CS-AKI. Goal-directed therapy has been considered to be a preventive strategy with a substantial level of efficacy. Many pharmacologic agents were tested for any benefit to treat or prevent CS-AKI but the results were conflicting and evidences are still lacking. The present review will summarize the current updated evidences about the risk factors and preventive strategies for CS-AKI.

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Polymyxin Acute Kidney Injury: Dosing and Other Strategies to Reduce Toxicity

Antibiotics ◽

10.3390/antibiotics8010024 ◽

2019 ◽

Vol 8 (1) ◽

pp. 24 ◽

Cited By ~ 16

Author(s):

Roger Nation ◽

Maria Rigatto ◽

Diego Falci ◽

Alexandre Zavascki

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Polymyxin B ◽

Multidrug Resistant ◽

Therapeutic Window ◽

Common Side Effect ◽

Dose Selection ◽

Dosing Strategies ◽

Risk Patients

Polymyxins are valuable antimicrobials for the management of multidrug-resistant Gram-negative bacteria; however, nephrotoxicity associated with these drugs is a very common side effect that occurs during treatment. This article briefly reviews nephrotoxic mechanisms and risk factors for polymyxin-associated acute kidney injury (AKI) and discusses dosing strategies that may mitigate kidney damage without compromising antimicrobial activity. Polymyxins have a very narrow therapeutic window and patients requiring treatment with these drugs are frequently severely ill and have multiple comorbidities, which increases the risk of AKI. Notably, there is a significant overlap between therapeutic and toxic plasma polymyxin concentrations that substantially complicates dose selection. Recent dosing protocols for both colistin and polymyxin B have been developed and may help fine tune dose adjustment of these antibiotics. Minimizing exposure to modifiable risk factors, such as other nephrotoxic agents, is strongly recommended. The dose should be carefully selected, particularly in high-risk patients. The administration of oxidative stress-reducing drugs is a promising strategy to ameliorate polymyxin-associated AKI, but still requires support from clinical studies.

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Acute kidney injury after cardiac surgery in children

Patologiya krovoobrashcheniya i kardiokhirurgiya ◽

10.21688/1681-3472-2021-4-11-22 ◽

2021 ◽

Vol 25 (4) ◽

pp. 11

Author(s):

S. A. Sergeev ◽

V. V. Lomivorotov

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Conflict Of Interest ◽

Kidney Injury ◽

Tissue Inhibitor Of Metalloproteinase ◽

Paediatric Cardiac Surgery ◽

Severe Stage ◽

Prevention And Treatment

Acute kidney injury (AKI) after cardiac surgery in children remains a common clinical concern. The approaches developed recently and applied in clinical practice have sufficiently helped in clarifying the epidemiology, risk factors and pathophysiology of AKI in paediatric cardiac surgery. Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria (pRIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease: Improving Global Outcomes (KDIGO), which are based on changes in serum creatinine levels and urine output rate, enable the identification and ranking of AKI according to severity. However, the diagnostic strategies for AKI have developed beyond creatinine levels and recommend the use of markers of renal tissue damage. Currently, two markers, neutrophil gelatinase-associated lipocalin and TIMP-2/IGFBP-7 (tissue inhibitor of metalloproteinase 2 and protein that binds insulin-like growth factor-7), can be used for the early diagnosis of AKI in paediatric cardiac surgery. Various risk factors, both renal and extrarenal, can predict AKI after cardiac surgery, among which age, the duration of cardiopulmonary bypass and the need for mechanical ventilation and inotropic support before surgery, are the most significant. Strategies for addressing modifiable risk factors (maintaining appropriate perfusion pressure during cardiopulmonary bypass and avoiding nephrotoxic drugs and fluid overload) will reduce the risk of developing AKI. There has been a significant increase in survival rates due to the introduction of ultrafiltration techniques and the early initiation of renal replacement therapy in the postoperative period. The purpose of this review is to analyse the current literature data on AKI in paediatric cardiac surgery. The review results demonstrate the differences in the incidence of AKI associated with cardiac surgery and the effectiveness of certain methods for prevention and treatment of this complication. Further comprehensive research on the issue of AKI in children, creation of medical electronic databases on patients, minimisation of the influence of possible risk factors and timely prevention and treatment of complications would prevent the development of AKI and reduce the possibility of complication progression to a more severe stage.Received 12 April 2021. Revised 24 June 2021. Accepted 25 June 2021.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Contribution of the authors: The authors contributed equally to this article.

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Subclinical Contrast-Induced Acute Kidney Injury in Patients Undergoing Cerebral Computed Tomography

Cardiorenal Medicine ◽

10.1159/000505422 ◽

2020 ◽

Vol 10 (2) ◽

pp. 125-136 ◽

Cited By ~ 3

Author(s):

Andrea Breglia ◽

Ilaria Godi ◽

Grazia Maria Virzì ◽

Gabriele Guglielmetti ◽

Giuseppe Iannucci ◽

...

Keyword(s):

Acute Kidney Injury ◽

Contrast Media ◽

Contrast Medium ◽

Kidney Injury ◽

Tissue Inhibitor Of Metalloproteinase ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Increased Risk ◽

Cerebral Computed Tomography ◽

Novel Biomarkers ◽

Neutrophil Gelatinase

Introduction: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. Objective: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. Methods: This is a prospective observational monocentric study. Urinary sample was collected at 4–8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. Results: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman’s rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16–17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. Conclusions: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.

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