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Correction of intravascular hypovolemia is a key component of the prevention and management of acute kidney injury (AKI), but excessive fluid administration is associated with poor outcomes, including the development and progression of AKI. There is growing evidence that fluid administration should be individualized and take into account patient characteristics, nature of the acute illness and trajectories, and risks and benefits of fluids. Existing data support the preferential use of buffered solutions for fluid resuscitation of patients at risk of AKI who do not have hypochloremia. There is a limited role for albumin, and starches should be avoided. Fluids should only be administered until intravascular hypovolemia has been corrected and euvolemia has been achieved using the minimum amount of fluid required to achieve and maintain euvolemia. Oliguria alone should not be viewed as a trigger for fluid administration. If fluid overload occurs, fluid therapy needs to be discontinued, and fluid removal using diuretic agents or extracorporeal therapies should be considered. [ABSTRACT FROM AUTHOR]

Aims: To evaluate sex‐specific disparities in acute kidney injury (AKI) complicating acute myocardial infarction‐related cardiogenic shock (AMI‐CS) in the United States. Methods and results: This was a retrospective cohort study from 2000 to 2014 from the National Inpatient Sample (20% sample of all hospitals in the United States). Patients >18 years admitted with a primary diagnosis of AMI and concomitant CS that developed AKI were included. The endpoints of interest were the prevalence, trends, and outcomes of men and women with AKI in AMI‐CS. Multivariable hierarchical logistic regression was used to control for confounding, and a two‐sided P < 0.05 was considered statistically significant. During this 15 year period, 440 257 admissions with AMI‐CS met the inclusion criteria, with AKI noted in 155 610 (35.3%). Women constituted 36.3% of the cohort and were older, of non‐White race, and with higher co‐morbidity compared with men. Women with AKI less often received coronary angiography (59% vs. 66%), percutaneous coronary intervention (39% vs. 43%), mechanical circulatory support (39% vs. 48%), mechanical ventilation (49% vs. 54%), and haemodialysis (9% vs. 10%) compared with men (all P < 0.001). Adjusted in‐hospital mortality was higher in women—odds ratio 1.16 (95% confidence interval 1.14–1.19); P < 0.001—compared with men. Women had shorter lengths of stay (12 ± 14 vs. 13 ± 14 days), lower hospital costs ($150 071 ± 180 796 vs. $181 260 ± 209 674), and were less often discharged to home (19% vs. 31%) (all P < 0.001). Conclusions: Women with AKI in AMI‐CS received fewer cardiac and non‐cardiac interventions, had higher in‐hospital mortality, and were less often discharged to home compared with men. [ABSTRACT FROM AUTHOR]

Main objectives: Echocardiographic parameters have been used to predict outcomes for specific intensive care unit (ICU) populations. We sought to define echocardiographic parameters for ICU patients receiving continuous renal replacement therapy (CRRT). Design, setting, participants, and measurements: This is a historical cohort study of consecutive ICU patients at Mayo Clinic (Rochester, Minnesota) who received CRRT from December 9, 2006, through November 13, 2015. Only patients with an echocardiographic examination within 7 days of CRRT initiation were considered. Results: The study included 1,276 patients. Decreased left ventricular ejection fraction (LVEF; ≤45%) was noted in 361/1,120 (32%) and increased right ventricular systolic pressure (RVSP; ≥40 mm Hg) was noted in 529/798 (66%). Right ventricular systolic dysfunction was observed in 320/820 (39%). The most common valvular abnormality was tricuspid regurgitation (244/1,276 [19%]). Stratification of these parameters by ICU type (medical, surgical, cardiothoracic, cardiac) showed that most echocardiographic abnormalities were significantly more prevalent among cardiac ICU patients: LVEF ≤45% (67/105 [64%]), RVSP ≥40 mm Hg (63/79 [80%]) and tricuspid regurgitation (50/130 [38%]). We compared patients with acute kidney injury (AKI) vs end-stage renal disease and showed that decreased LVEF (284/921 [31%] vs 78/201 [39%]), was significantly less prevalent among patients with AKI, but increased RVSP was more prevalent (445/651 [68%] vs 84/147 [57%]) with AKI. Conclusions: ICU patients who required CRRT had increased prevalence of pulmonary hypertension and right and left ventricular systolic dysfunction. Prediction of adverse outcomes with echocardiographic parameters in this patient population can lead to identification of modifiable risk factors. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a very common complication of acute illnesses and is associated with poor short- and long-term outcomes [[1]]. Modifications of the AKI clinical course may be achievable by biomarker-guided timely adjustment of disease-modifying, patient-specific interventions according to Kidney Disease: Improving Global Outcomes (KDIGO) bundle [[13]]. In only one-fourth of patients, AKI reversal was complete or near-complete within 7 days, another fourth did not recover, about 10% had a late reversal, and the remaining patients relapsed after AKI reversal, with (22%) or without (15%) ultimate recovery. [Extracted from the article]

Background: To evaluate the clinical features and outcomes of acute cardiorenal syndrome type-5 in patients with severe sepsis and septic shock. Methods: Historical cohort study of all adult patients with severe sepsis and septic shock admitted to the intensive care units (ICU) at Mayo Clinic Rochester from January 1, 2007 through December 31, 2014. Patients with prior renal or cardiac dysfunction were excluded. Patients were divided into groups with and without cardiorenal syndrome type-5. Acute Kidney Injury (AKI) was defined by both serum creatinine and urine output criteria of the AKI Network and the cardiac injury was determined by troponin-T levels. Outcomes included in-hospital mortality, ICU and hospital length of stay, and one-year survival. Results: Of 602 patients meeting the study inclusion criteria, 430 (71.4%) met criteria for acute cardiorenal syndrome type-5. Patients with cardiorenal syndrome type-5 had higher severity of illness, greater vasopressor and mechanical ventilation use. Cardiorenal syndrome type-5 was associated higher unadjusted in-hospital mortality, ICU and hospital lengths of stay, and lower one-year survival. When adjusted for age, gender, severity of illness and mechanical ventilation, cardiorenal syndrome type-5 was independently associated with 1.7-times greater odds of in-hospital mortality (p = .03), but did not predict one-year survival (p = .06) compared to patients without cardiorenal syndrome. Conclusions: In sepsis, acute cardiorenal syndrome type-5 is associated with worse in-hospital mortality compared to patients without cardiorenal syndrome. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common after coronary artery bypass grafting (CABG) and is associated with poor outcome. Increased hospital procedure volume has been associated with better outcomes. However, the impact of hospital CABG volume on AKI needing dialysis (AKI-D) is less clear. We designed this study to examine (i) the impact of number of annual CABG procedures per hospital (CABG-vol) on AKI-D and inpatient mortality and (ii) if it modifies the relationship between AKI-D and mortality. Methods: Using the Nationwide Inpatient Sample database from 2000 to 2010, we identified admissions with CABG and those with AKI-D using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Multivariable logistic regressions were used to assess the impact of CABG-vol on AKI-D and mortality. We used restricted cubic splines to account for the nonlinear relationship between CABG-vol and mortality. We also evaluated the a priori interaction term between CABG-vol and AKI-D in the model for mortality. Results: Of 4 002 730 hospitalizations for CABG, 0.7% (24 126) had AKI-D. On adjusted analysis, CABG-vol did not correlate with odds of developing AKI-D [odds ratio (OR) 0.99; 95% confidence interval (CI) 0.99-1.00] but was associated with mortality, though the association was nonlinear. AKI-D was a significant predictor of mortality with OR 7.58 (95% CI 6.81-8.44). The interaction of CABG-vol and AKI-D was not significant (P=0.8). Conclusions: Lower annual CABG hospital procedure volume is significantly associated with higher mortality but not with a higher incidence of AKI-D. AKI-D is associated with higher mortality in those undergoing CABG. However, there is no differential effect of hospital volume on odds of mortality due to AKI-D [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in hospitalized patients and is associated with increased morbidity, mortality, and cost. Currently, AKI is diagnosed after symptoms manifest; available diagnostic tests (e.g., serum creatinine, urine microscopy, urine output) have limited ability to identify subclinical AKI. Because of the lack of treatment strategies, AKI typically is managed with supportive measures. However, strategies exist that may prevent renal insults in critically ill patients; therefore, early recognition of AKI is crucial for minimizing damage propagation. Content: Experimental and clinical studies have identified biomarkers that may facilitate earlier recognition of AKI or even identify patients at risk of AKI. Such biomarkers might aid in earlier implementation of preventive strategies to slow disease progression and potentially improve outcomes. This review describes some of the most promising novel biomarkers of AKI, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (lL-18), liver-type fatty-acid-binding protein (L-FABP), insulin-like-growth-factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinase 2 (TIMP-2). Summary: We discuss biomarker test characteristics, their strengths and weaknesses, and future directions of their clinical implementation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Given the known deleterious effects seen with bicarbonate supplementation for acidemia, we hypothesized that utilizing high bicarbonate concentration replacement solution in continuous venovenous hemofiltration (CVVH) would be independently associated with higher mortality. Methods: In a propensity score-matched historical cohort study conducted at a single tertiary care center from December 9, 2006, through December 31, 2009, a total of 287consecutive adult critically ill patients with Stage III acute kidney injury (AKI) requiring CVVH were enrolled. We excluded patients on maintenance dialysis, those who received other modalities of continuous renal replacement therapies, and patients that received a mixed of 22 and 32 mEq/L bicarbonate solution pre- and post-filter. The primary outcome was in-hospital and 90-day mortality rates. Results: Among enrollees, 68 were used 32 mEq/L bicarbonate solution, and 219 received 22mEq/L bicarbonate solution for CVVH. Patients on 32 mEq/L bicarbonate solution were more often non-surgical, had lower pH and bicarbonate level but had higher blood potassium and phosphorus levels in comparison with those on 22 mEq/L bicarbonate solution. After adjustment for the baseline characteristics, the use of 32 bicarbonate solution was significantly associated with increased in-hospital (HR = 1.94; 95% CI 1.02–3.79) and 90-day mortality (HR = 1.50; 95% CI 1.03–2.14). There was a significant increase in the hospital (p = .03) and 90-day (p = .04) mortality between the 22 vs. 32 mEq/L bicarbonate solution groups following propensity matching. Conclusion: Our data showed there is a strong association between using high bicarbonate solution and mortality independent of severity of illness and comorbid conditions. These findings need to be evaluated further in prospective studies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to examine the association between renal recovery status at hospital discharge after acute kidney injury (AKI) and long-term mortality following transcatheter aortic valve replacement (TAVR). Methods: We screened all adult patients who survived to hospital discharge after TAVR for aortic stenosis at a quaternary referral medical center from January 1, 2008, through June 30, 2014. An AKI was defined as an increase in serum creatinine level of 0.3 mg/dL or a relative increase of 50% from baseline. Renal outcome at the time of discharge was evaluated by comparing the discharge serum creatinine level to the baseline level. Complete renal recovery was defined as no AKI at discharge, whereas partial renal recovery was defined as AKI without a need for renal replacement therapy at discharge. No renal recovery was defined as a need for renal replacement therapy at discharge. Results: The study included 374 patients. Ninty-eight (26%) patients developed AKI during hospitalization: 55 (56%) had complete recovery; 39 (40%), partial recovery; and 4 (4%), no recovery. AKI development was significantly associated with increased risk of 2-year mortality (hazard ratio [HR], 2.20 [95% CI, 1.37–3.49]). For patients with AKI, the 2-year mortality rate for complete recovery was 34%; for partial recovery, 43%; and for no recovery, 75%; compared with 20% for patients without AKI (P < .001). In adjusted analysis, complete recovery (HR, 1.87 [95% CI, 1.03–3.23]); partial recovery (HR, 2.65 [95% CI, 1.40–4.71]) and no recovery (HR, 10.95 [95% CI, 2.59–31.49]) after AKI vs no AKI were significantly associated with increased risk of 2-year mortality. Conclusion: The mortality rate increased for all patients with AKI undergoing TAVR. A reverse correlation existed for progressively higher risk of death and the extent of AKI recovery. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death. These novel AKI biomarkers complement serum creatinine (SCr) and urine output, which are the standard diagnostic tools for AKI detection. In this article, we review the available literature on characteristics of promising AKI biomarkers that are currently the focus of preclinical and clinical investigations. These biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein, interleukin 18 (lL-18), insulin-like growth factor-binding protein 7, tissue inhibitor of metalloproteinase 2 (TIMP-2), calprotectin, urine angiotensinogen (AGT), and urine microRNA. We then describe the clinical performance of these biomarkers for diagnosis and prognostication. We also appraise each AKI biomarker's advantages and limitations as a tool for early AKI recognition and prediction of clinical outcomes after AKI. Finally, we review the current and future states of implementation of biomarkers in the clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Frailty is a common condition in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). The aim of this systematic review was to assess the impact of frailty status on acute kidney injury (AKI) and mortality after TAVR. Methods: A systematic literature search was conducted using MEDLINE, EMBASE, and Cochrane databases from the inception through November 2016. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016052350). Studies that reported odds ratios, relative risks or hazard ratios comparing the risk of AKI after TAVR in frail vs. non-frail patients were included. Mortality risk was evaluated among the studies that reported AKI-related outcomes. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: Eight cohort studies with a total of 10,498 patients were identified and included in the meta-analysis. The pooled RR of AKI after TAVR among the frail patients was 1.19 (95% CI 0.97–1.46, I2 = 0), compared with non-frail patients. When the meta-analysis was restricted only to studies with standardized AKI diagnosis according to Valve Academic Research Consortium (VARC)-2 criteria, the pooled RRs of AKI in frail patients was 1.16 (95% CI 0.91–1.47, I2 = 0). Within the selected studies, frailty status was significantly associated with increased mortality (RR 2.01; 95% CI 1.44–2.80, I2 = 58). Conclusion: The findings from our study suggest no significant association between frailty status and AKI after TAVR. However, frailty status is associated with mortality after TAVR and may aid appropriate patient selection for TAVR. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication of acute illnesses with significant impact on the mortality and morbidity. Early recognition of AKI allows clinicians to provide prophylactic interventions and to improve the outcomes of this deadly syndrome. Growing utilization and capabilities of electronic health records allow AKI risk stratification and early recognition with a potential effect on the processes of care and outcomes. We evaluate the current level of evidence on the impact of the AKI e-alert on the processes of care and outcomes. We then discuss the impacts of e-alerting in the design of the future of nephrology service within the hospital practices with suggestions regarding the role of nephrologists in management of AKI e-alert systems in order to improve the quality of care provided to AKI patients. [ABSTRACT FROM AUTHOR]

Background: Although 28% to 49% of severe sepsis hospitalizations have been described as being "culture negative," there are very limited data on the epidemiology and outcomes of those with culture-negative severe sepsis (CNSS). The objectives of this study were to investigate the proportion and trends of CNSS and its association with mortality.Methods: Using the Nationwide Inpatient Sample (NIS) database from 2000 to 2010, we identified adults hospitalized with severe sepsis. Those without any specific organism codes were identified as "with CNSS." We examined the proportion of CNSS hospitalizations and rates of mortality associated with it. We also assessed the independent effect of CNSS on mortality.Results: Of 6,843,279 admissions of patients with severe sepsis, 3,226,406 (47.1%) had culture-negative results. The age-adjusted proportion of CNSS increased from 33.9% in 2000 to 43.5% in 2010 (P < .001). Those with CNSS had more comorbidities, acute organ dysfunction (respiratory, cardiac, hepatic, and renal dysfunction), and in-hospital mortality (34.6% vs 22.7%; P < .001), although acute kidney injury requiring dialysis was less frequent (5.3% vs 6.1%; P < .001). CNSS was an independent predictor of mortality in those with severe sepsis (OR, 1.75; 95% CI, 1.72-1.77).Conclusions: CNSS among hospitalized patients is common, and its proportion is on the rise. CNSS is associated with greater acute organ dysfunction and mortality. Having CNSS is an independent predictor of death. [ABSTRACT FROM AUTHOR]

Aim This study aimed to determine the incidence and risk factors of acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR). Methods We included all adult patients undergoing TAVR for aortic stenosis from 1 January 2008 to 30 June 2014 at a tertiary referral hospital. AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. We performed a multivariate logistic regression to identify factors associated with post-procedural AKI occurrence. Results Three hundred eighty-six patients met the inclusion criteria, of which 106 (28%) developed AKI. In multivariate analysis, AKI development was independently associated with a transapical approach (odds ratio (OR), 2.81; 95% confidence interval (CI), 1.72-4.65 compared with transfemoral approach) and the need for an intra-aortic balloon pump (OR, 9.11; 95% CI, 1.77-68.29). Higher baseline renal function (OR, 0.78 per 10 mL/min per 1.73 m2 increment in glomerular filtration rate; 95% CI, 0.68-0.87) was significantly associated with a decreased risk of AKI. After adjustment for the Society of Thoracic Surgeons' risk score, post-procedural AKI development remained significantly associated with an increased in-hospital (OR, 4.74; 95% CI, 1.39-18.48) and 6-month mortality (OR, 4.66; 95% CI, 2.32-9.63). Conclusion In a cohort of patients undergoing TAVR for aortic stenosis, AKI commonly occurred and was significantly associated with increased mortality. Baseline renal function, procedure approach and the need for circulatory support were important predictive factors for post-procedural AKI occurrence. [ABSTRACT FROM AUTHOR]

Objective The goal of this systematic review was to assess the effects of contrast media volume on transcatheter aortic valve replacement-related acute kidney injury. Methods A literature search was performed using Medline, EMbase, the Cochrane Database of Systematic Reviews, and from the inception of these databases through December 2015. Studies that reported relative risk, odds ratio, or hazard ratio comparing the risks of acute kidney injury following transcatheter aortic valve replacement in patients who received high contrast media volume were included. Pooled risk ratio (RR) and 95% confidence intervals (95% CI) were calculated using a random-effect, generic inverse variance method. Results Four cohort studies composed of 891 patients were included in the analyses to assess the risk of acute kidney injury after transcatheter aortic valve replacement in patients who received high contrast media volume. The pooled RR of acute kidney injury after transcatheter aortic valve replacement in patients who received a large volume of contrast media was 1.41 (95% CI, 0.87 to 2.28) compared with low contrast media volume. The meta-analysis was limited to studies using standard acute kidney injury definitions, and the pooled RR of acute kidney injury in patients who received high contrast media volume is 1.12 (95% CI, 0.78 to 1.62). Conclusion Our meta-analysis shows no significant association between contrast media volume and risk of acute kidney injury after transcatheter aortic valve replacement. [ABSTRACT FROM AUTHOR]

Background: Baseline serum creatinine (SCr) level is frequently not measured in clinical practice. The aim of this study was to investigate the effect of various methods of baseline SCr determination measurement on accuracy of acute kidney injury (AKI) diagnosis in critically ill patients.Methods: This was a retrospective cohort study. All adult intensive care unit (ICU) patients admitted at a tertiary referral hospital from January 1, 2011 through December 31, 2011, with at least one measured SCr value during ICU stay, were included in this study. The baseline SCr was considered either an admission SCr (SCrADM) or an estimated SCr, using MDRD formula, based on an assumed glomerular filtration rate (GFR) of 75 ml/min/1.73 m(2) (SCrGFR-75). Determination of AKI was based on the KDIGO SCr criterion. Propensity score to predict the likelihood of missing SCr was used to generate a simulated cohort of 3566 patients with baseline outpatient SCr, who had similar characteristics with patients whose outpatient SCr was not available.Results: Of 7772 patients, 3504 (45.1 %) did not have baseline outpatient SCr. Among patients without baseline outpatient SCr, AKI was detected in 571 (16.3 %) using the SCrADM and 997 (28.4 %) using SCrGFR-75 (p < .001). Compared with non-AKI patients, patients who met AKI only by SCrADM, but not SCrGFR-75, were significantly associated with 60-day mortality (OR 2.90; 95 % CI 1.66-4.87), whereas patients who met AKI only by SCrGFR-75, but not SCrADM, had a non-significant increase in 60-day mortality risk (OR 1.33; 95 % CI 0.94-1.88). In a simulated cohort of patients with baseline outpatient SCr, SCrGFR-75 yielded a higher sensitivity (77.2 vs. 50.5 %) and lower specificity (87.8 vs. 94.8 %) for the AKI diagnosis in comparison with SCrADM.Conclusions: When baseline outpatient SCr was not available, using SCrGFR-75 as surrogate for baseline SCr was found to be more sensitive but less specific for AKI diagnosis compared with using SCrADM. This resulted in higher incidence of AKI with larger likelihood of false-positive cases. [ABSTRACT FROM AUTHOR]

Aim This study aimed to investigate how varied methods of determining baseline serum creatinine ( SCr) would affect acute kidney injury ( AKI) diagnosis and prediction of 60 day mortality in critically ill patients following an episode of AKI. Methods This is a single-centre retrospective study conducted at a tertiary referral hospital. All adult intensive care unit ( ICU) patients between January and December 2011, who had at least one SCr values measured between 7 days and 180 days before hospital admission and during ICU stay, were analyzed. The baseline SCr was calculated using either the most recent ( SCrmost recent) or the minimum (SCrmin) value of SCr measurement over the specified assessment period before hospital admission. AKI was defined based on KDIGO SCr definition. The primary outcome was 60 day mortality after ICU admission. Results A total of 4020 patients were included in the analysis. AKI was detected in 1204 (30.0%) using the SCrmin and 945 (23.5%) using the SCrmost recent ( P < 0.001). Compared with patients without AKI regardless of baseline SCr methodology, the 60 day mortality risk of patients who developed AKI using the SCrmin and SCrmost recent was significantly increased (odds ratio ( OR) = 3.74; 95% confidence interval ( CI) 2.98-4.70). Similarly, the risk of 60 day mortality in patients who met AKI criteria using the SCrmin but not the SCrmost recent was significant higher than in patients without AKI ( OR = 2.04; 95% CI 1.36-3.00). Conclusion Using the minimum value of preadmission SCr as a baseline kidney function not only can detect more AKI cases, but also provides the better predictive ability for 60 day mortality. [ABSTRACT FROM AUTHOR]

Background In the current acute kidney injury (AKI) definition, the urine output (UO) criterion does not specify which body weights (BW), i.e. actual (ABW) versus ideal (IBW), should be used to diagnose and stage AKI, leading to heterogeneity across research studies. Methods This is a single center, retrospective, observational study conducted at a tertiary referral hospital. All adult patients who were admitted to intensive care units (ICUs) at our institution for a minimum of 6 continuous hours between January and March 2010 and had a urinary catheter for hourly urine output monitoring were eligible for this study. Patients' AKI stages, based on UO criterion, were assessed by calculating each milliliter of urine per kilogram per hour, using ABW versus IBW. Results A total of 493 ICU patients were included in the analysis. The median ABW and IBW were 82 (IQR 68-96) and 70 (IQR 60-77) kg, respectively. Using the IBW criterion, 154 patients (31.2%) were diagnosed with AKI, while 204 (41.4%) were diagnosed using the ABW measurement (P-value < .01). Patients who had AKI regardless of BW type had an adjusted odds ratio of 1.76 (95% CI 1.05-2.95) for 90-day mortality, whereas patients who had AKI according to ABW but not IBW had no significant increase in the risk of 90-day mortality, adjusted OR 0.76; (95% CI 0.25-1.91), compared to patients who had no AKI. Conclusions Using ABW to diagnose and stage AKI by UO criterion is more sensitive and less specific than IBW. Based on the application of the definition, different BW types could be utilized. [ABSTRACT FROM AUTHOR]

Background Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers. Methods We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease: Improving Global Outcomes Stages 2–3 AKI within 12 h using data from a previously published multicenter cohort (Sapphire). Next, we verified these cutoffs in a new study (Opal) enrolling 154 critically ill adults from six sites in the USA. Results One hundred subjects (14%) in Sapphire and 27 (18%) in Opal met the primary end point. The results of the Opal study replicated those of Sapphire. Relative risk (95% CI) in both studies for subjects testing at ≤0.3 versus >0.3–2 were 4.7 (1.5–16) and 4.4 (2.5–8.7), or 12 (4.2–40) and 18 (10–37) for ≤0.3 versus >2. For the 0.3 cutoff, sensitivity was 89% in both studies, and specificity 50 and 53%. For 2.0, sensitivity was 42 and 44%, and specificity 95 and 90%. Conclusions Urinary [TIMP-2]•[IGFBP7] values of 0.3 or greater identify patients at high risk and those >2 at highest risk for AKI and provide new information to support clinical decision-making. Clinical Trials Registration Clintrials.gov # NCT01209169 (Sapphire) and NCT01846884 (Opal). [ABSTRACT FROM PUBLISHER]

Introduction: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP- 2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. [ABSTRACT FROM AUTHOR]

Background: To examine the relationship between delta mean arterial pressure (ΔMAP; MAP change between pre-admission minus post-resuscitation) and acute kidney injury (AKI) among patients with septic shock. In this retrospective, single-center cohort study of adult patients pre-admission MAP is defined as the median MAP recorded from 365 to 7 days before admission. Post-resuscitation MAP was median MAP during the 7th hour after initiating resuscitation.Results: In our cohort (N = 233; 55% male), the median (interquartile range [IQR]) age was 71 (58-81) years and the median (IQR) acute physiology, age, chronic health evaluation (APACHE) III score was 81 (66-97). Although those in the lowest ΔMAP quartile (−24.5 to 3.9 mmHg) had no demographic differences compared with the rest of the cohort, the odds ratio for AKI was 0.26 (95% CI 0.11-0.57) after adjustment for other known AKI risk factors. Among patients with a history of hypertension, the lowest quartile had an odds ratio for AKI of 0.12 (95% CI 0.04-0.37) after adjusting for risk factors for AKI in this cohort.Conclusions: The incidence of AKI was lowest among those whose post-resuscitation MAP was closest to or higher than their pre-admission MAP. Further study regarding the effect of targeting the pre-admission MAP for post-resuscitation on the incidence of AKI is warranted. [ABSTRACT FROM AUTHOR]

Objectives: Decreased urine output and/or increased serum creatinine may herald the development of acute kidney injury or reflect normal physiology. In this secondary analysis of the Sapphire study, we examined biomarkers of cell cycle arrest in the settings of oliguria and/or azotemia to improve risk assessment when used with conventional indices in predicting severe acute kidney injury (Kidney Disease: Improving Global Outcomes 3 defined by the need for renal replacement therapy or changes in urine output, serum creatinine or both) or death.Design: Prospective, international, Sapphire study.Setting: Academic Medical Center.Patients: Patients without acute kidney injury Kidney Disease: Improving Global Outcomes stage 2 or 3.Interventions: None.Measurements and Main Results: The primary endpoint being development of severe acute kidney injury or death within 1 week. Secondary analysis examined the relationship between tissue inhibitor of metalloproteinases-2 ([TIMP-2]) and insulin growth factor binding protein 7 ([IGFBP7]) and 9-month death or dialysis conditioned on progression to stage 2-3 acute kidney injury within 1 week. Seventy-nine patients reached the primary endpoint and were more likely to be surgical, with higher nonrenal Acute Physiology and Chronic Health Evaluation III scores and more chronic kidney disease. Stage 1 urine output, serum creatinine, and urinary [TIMP-2]•[IGFBP7] greater than 2.0 were all predictive of progression to the primary endpoint independent from nonrenal Acute Physiology and Chronic Health Evaluation III score. Combinations of predictors increased the hazard ratios considerably (from 2.17 to 4.14 to 10.05, respectively). In the presence of acute kidney injury (stage 1), [TIMP-2]•[IGFBP7] greater than 2.0 leads to an increased risk of death or dialysis at 9 months even in the absence of progression of acute kidney injury (stage 2-3) within 7 days.Conclusions: Cell cycle arrest biomarkers, TIMP-2 and IGFBP7, improve risk stratification for severe outcomes in patients with stage 1 acute kidney injury by urine output, serum creatinine or both, with risk increasing with each acute kidney injury indicator. Longer term outcomes demonstrate that the associated risks of a [TIMP-2]•[IGFBP7] greater than 2.0 is equivalent to acute kidney injury progression even where no progression from stage 1 acute kidney injury is observed. [ABSTRACT FROM AUTHOR]

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy.Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial.Setting: ICUs.Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively).Interventions: IV angiotensin II or placebo.Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively.Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b We hypothesized that acute kidney injury (AKI) in intensive care unit (ICU) patients is associated with major adverse kidney events (MAKE). B Results: b KDIGO classified 83% of patients as non-AKI (stages 0 or 1) and 17% of patients as having AKI (stages 2 or 3). We found a significantly higher incidence of MAKE30, MAKE60, and MAKE90 among patients with AKI when compared with the non-AKI group (p<0.0001 for all time points). [Extracted from the article]