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1.  Plasma neutrophil gelatinase-associated lipocalin in acute kidney injury superimposed on chronic kidney disease after cardiac surgery: a multicenter prospective study 
Critical Care  2013;17(6):R270.
Introduction
Plasma neutrophil gelatinase-associated lipocalin (NGAL) is reportedly useful for post-cardiac surgery acute kidney injury (AKI). Although chronic kidney disease (CKD) is a strong risk factor for AKI development, no clinical evaluation of plasma NGAL has specifically examined AKI occurring in patients with CKD. This study evaluated plasma NGAL in AKI superimposed on CKD after cardiac surgery.
Methods
This study prospectively evaluated 146 adult patients with scheduled cardiac surgery at 2 general hospitals. Plasma NGAL was measured before surgery, at ICU arrival after surgery (0 hours), and 2, 4, 12, 24, 36, and 60 hours after ICU arrival.
Results
Based on the Kidney Disease Improving Global Outcomes (KDIGO) CKD guideline, 72 (49.3%) were diagnosed as having CKD. Of 146 patients, 53 (36.3%) developed AKI after surgery. Multiple logistic regression analysis revealed that preoperative plasma NGAL, estimated glomerular filtration rate (eGFR), and operation time are significantly associated with AKI occurrence after surgery. Plasma NGAL in AKI measured after surgery was significantly higher than in non-AKI irrespective of CKD complication. However, transient decrease of plasma NGAL at 0 to 4 hours was observed especially in AKI superimposed on CKD. Plasma NGAL peaked earlier than serum creatinine and at the same time in mild AKI and AKI superimposed on CKD with increased preoperative plasma NGAL (>300 ng/ml). Although AKI superimposed on CKD showed the highest plasma NGAL levels after surgery, plasma NGAL alone was insufficient to discriminate de novo AKI from CKD without AKI after surgery. Receiver operating characteristics analysis revealed different cutoff values of AKI for CKD and non-CKD patients.
Conclusions
Results show the distinct features of plasma NGAL in AKI superimposed on CKD after cardiac surgery: 1) increased preoperative plasma NGAL is an independent risk factor for post-cardiac surgery AKI; 2) plasma NGAL showed an earlier peak than serum creatinine did, indicating that plasma NGAL can predict the recovery of AKI earlier; 3) different cutoff values of post-operative plasma NGAL are necessary to detect AKI superimposed on CKD distinctly from de novo AKI. Further investigation is necessary to confirm these findings because this study examined a small number of patients.
doi:10.1186/cc13104
PMCID: PMC4056897  PMID: 24215663
2.  Acute kidney injury following transcatheter aortic valve implantation: predictive factors, prognostic value, and comparison with surgical aortic valve replacement 
European Heart Journal  2009;31(7):865-874.
Aims
Very few data exist on the occurrence of acute kidney injury (AKI) associated with transcatheter aortic valve implantation (TAVI). The objectives of the present study were (i) to determine the incidence, predictive factors, and prognostic value of AKI following TAVI, and (ii) to compare the occurrence of AKI in TAVI vs. surgical aortic valve replacement (SAVR) in patients with pre-procedural chronic kidney disease (CKD).
Methods and results
A total of 213 patients (mean age 82 ± 8 years) undergoing TAVI for the treatment of severe aortic stenosis were included in the study. Acute kidney injury was defined as a reduction of >25% in estimated glomerular filtration rate (eGFR) within 48 h following the procedure or the need for haemodialysis during index hospitalization. Those patients with pre-procedural CKD (eGFR <60 mL/min/1.73 m2, n = 119) were compared with 104 contemporary patients with CKD who underwent isolated SAVR. The incidence of AKI following TAVI was 11.7%, with 1.4% of the patients requiring haemodialysis. Predictive factors of AKI were hypertension (OR: 4.66; 95% CI: 1.04–20.87), chronic obstructive pulmonary disease (OR: 2.64, 95% CI: 1.10–6.36), and peri-operative blood transfusion (OR: 3.47, 95% CI: 1.30–9.29). Twenty-one patients (9.8%) died during index hospitalization, and the logistic EuroSCORE (OR: 1.03 for each increase of 1%; 95% CI: 1.01–1.06) and occurrence of AKI (OR: 4.14, 95% CI: 1.42–12.13) were identified as independent predictors of postoperative mortality. Patients with CKD who underwent TAVI were older, had a higher logistic EuroSCORE and lower pre-procedural eGFR values compared with those who underwent SAVR (P < 0.0001 for all). The incidence of AKI was lower (P = 0.001; P = 0.014 after propensity score adjustment) in CKD patients who underwent TAVI (9.2%, need for haemodialysis: 2.5%) compared with those who underwent SAVR (25.9%, need for haemodialysis: 8.7%).
Conclusion
Acute kidney injury occurred in 11.7% of the patients following TAVI and was associated with a greater than four-fold increase in the risk of postoperative mortality. Hypertension, chronic obstructive pulmonary disease, and blood transfusion were predictive factors of AKI. In those patients with pre-procedural CKD, TAVI was associated with a significant reduction of AKI compared with SAVR.
doi:10.1093/eurheartj/ehp552
PMCID: PMC2848323  PMID: 20037180
Aortic stenosis; Transcatheter aortic valve implantation; Acute renal failure; Surgical aortic valve replacement
3.  Brain natriuretic peptide levels have diagnostic and prognostic capability for cardio-renal syndrome type 4 in intensive care unit patients 
Critical Care  2009;13(3):R70.
Introduction
Limited data are available regarding the diagnostic and prognostic utility of brain natriuretic peptide (BNP) in patients with chronic kidney disease (CKD) in the intensive care unit (ICU) setting.
Methods
All patients with CKD and a serum creatinine (Cr) of 2.0 mg/dl or higher admitted to the ICU between January 2006 and September 2007 were enrolled in this study. The CKD group was divided according to the presence or absence of acute decompensated heart failure (ADHF) into CKD + ADHF and CKD - ADHF groups, respectively. Other patients with ADHF having low Cr (<1.2 mg/dl) in the coronary care unit were also recruited as a control group during the same period. BNP levels at the time of admission (admission BNP) were compared amongst these groups. We then sought to determine whether BNP levels could predict the outcome in patients with CKD.
Results
Of 136 patients with CKD for whom data were available, including 58 on dialysis (42.6%), 81 (59.6%) had ADHF and their estimated glomerular filtration rate (eGFR) was 12.8 ± 7.3 ml/min/1.73 m2. BNP levels at admission were 2708.6 ± 1246.9, 567.9 ± 491.7 and 1418.9 ± 1126.5 pg/ml in the CKD + ADHF, CKD - ADHF and control groups (n = 33), respectively (P = 0.000). The optimal cutoff level in patients with CKD was 1020.5 pg/ml (area under the curve = 0.944) to detect ADHF from the receiver operating characteristic (ROC) curve. This level was not associated with in-hospital mortality, all-cause death or a composite event (all-cause death and/or new cardiac event). However, a borderline significant association was observed with new cardiac events (hazard ratio (HR) = 4.551; P = 0.078) during the follow-up period (521.1 ± 44.7 days). Furthermore, continuous variables of BNP and BNP quartiles were significantly associated with new cardiac events in the multivariate Cox model (HR = 1.001, P = 0.041; HR = 2.212, P = 0.018).
Conclusions
The findings suggest that the level of BNP at the time of admission may be a useful marker for detecting ADHF and predicting cardiac events in patients with CKD in the ICU setting.
doi:10.1186/cc7878
PMCID: PMC2717430  PMID: 19445682
4.  Association of Non-alcoholic Fatty Liver Disease with Chronic Kidney Disease: A Systematic Review and Meta-analysis 
PLoS Medicine  2014;11(7):e1001680.
In a systematic review and meta-analysis, Giovanni Musso and colleagues examine the association between non-alcoholic fatty liver disease and chronic kidney disease.
Please see later in the article for the Editors' Summary
Background
Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD.
Methods and Findings
English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69–2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65–1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58–4.05) and incidence (HR 2.12, 95% CI 1.42–3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14–8.61) and incidence (HR 3.29, 95% CI 2.30–4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies.
Conclusion
The presence and severity of NAFLD are associated with an increased risk and severity of CKD.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Chronic kidney disease (CKD)—the gradual loss of kidney function—is becoming increasingly common. In the US, for example, more than 10% of the adult population (about 26 million people) and more than 25% of individuals older than 65 years have CKD. Throughout life, the kidneys perform the essential task of filtering waste products (from the normal breakdown of tissues and from food) and excess water from the blood to make urine. CKD gradually destroys the kidneys' filtration units, the rate of blood filtration decreases, and dangerous amounts of waste products build up in the blood. Symptoms of CKD, which rarely occur until the disease is very advanced, include tiredness, swollen feet, and frequent urination, particularly at night. There is no cure for CKD, but progression of the disease can be slowed by controlling high blood pressure and diabetes (two risk factors for CKD), and by adopting a healthy lifestyle. The same interventions also reduce the chances of CKD developing in the first place.
Why Was This Study Done?
CKD is associated with an increased risk of end-stage renal (kidney) disease and of cardiovascular disease. These life-threatening complications are potentially preventable through early identification and treatment of CKD. Because early recognition of CKD has the potential to reduce its health-related burden, the search is on for new modifiable risk factors for CKD. One possible new risk factor is non-alcoholic fatty liver disease (NAFLD), which, like CKD is becoming increasingly common. Healthy livers contain little or no fat but, in the US, 30% of the general adult population and up to 70% of patients who are obese or have diabetes have some degree of NAFLD, which ranges in severity from simple fatty liver (steatosis), through non-alcoholic steatohepatitis (NASH), to NASH with fibrosis (scarring of the liver) and finally cirrhosis (extensive scarring). In this systematic review and meta-analysis, the researchers investigate whether NAFLD is a risk factor for CKD by looking for an association between the two conditions. A systematic review identifies all the research on a given topic using predefined criteria, meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 33 studies that assessed NAFLD and CKD in nearly 64,000 participants, including 20 cross-sectional studies in which participants were assessed for NAFLD and CKD at a single time point and 13 longitudinal studies in which participants were assessed for NAFLD and then followed up to see whether they subsequently developed CKD. Meta-analysis of the data from the cross-sectional studies indicated that NAFLD was associated with a 2-fold increased risk of prevalent (pre-existing) CKD (an odds ratio [OR]of 2.12; an OR indicates the chance that an outcome will occur given a particular exposure, compared to the chance of the outcome occurring in the absence of that exposure). Meta-analysis of data from the longitudinal studies indicated that NAFLD was associated with a nearly 2-fold increased risk of incident (new) CKD (a hazard ratio [HR] of 1.79; an HR indicates often a particular event happens in one group compared to how often it happens in another group, over time). NASH was associated with a higher prevalence and incidence of CKD than simple steatosis. Similarly, advanced fibrosis was associated with a higher prevalence and incidence of CKD than non-advanced fibrosis.
What Do These Findings Mean?
These findings suggest that NAFLD is associated with an increased prevalence and incidence of CKD and that increased severity of liver disease is associated with an increased risk and severity of CKD. Because these associations persist after allowing for established risk factors for CKD, these findings identify NAFLD as an independent CKD risk factor. Certain aspects of the studies included in this meta-analysis (for example, only a few studies used biopsies to diagnose NAFLD; most used less sensitive tests that may have misclassified some individuals with NAFLD as normal) and the methods used in the meta-analysis may limit the accuracy of these findings. Nevertheless, these findings suggest that individuals with NAFLD should be screened for CKD even in the absence of other risk factors for the disease, and that better treatment of NAFLD may help to prevent CKD.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001680.
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about all aspects of kidney disease; the US National Digestive Diseases Information Clearinghouse provides information about non-alcoholic liver disease
The US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories, and information on non-alcoholic fatty liver disease
The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish)
The not-for-profit UK National Kidney Federation provides support and information for patients with kidney disease and for their carers
The British Liver Trust, a not-for-profit organization, provides information about non-alcoholic fatty liver disease, including a patient story
doi:10.1371/journal.pmed.1001680
PMCID: PMC4106719  PMID: 25050550
5.  A Single-Centre Study of Acute Cardiorenal Syndrome: Incidence, Risk Factors and Consequences 
Cardiorenal Medicine  2012;2(3):168-176.
Objective
Cardiac and kidney diseases are common, and the impact of acute kidney injury (AKI) on patient outcome is well known. We aimed to investigate the incidence of acute cardiorenal syndrome (CRS) and the risk factors and outcomes associated with the disease.
Methods
We conducted a retrospective cohort study comprising 289 patients with acute coronary syndrome (ACS) and acute decompensated heart failure (ADHF), examining the incidence of AKI defined according to the Acute Kidney Injury Network (AKIN) classification, the factors contributing to AKI, and the impact of AKI on in-hospital mortality and hospital re-admission.
Results
Of 71 patients with AKI, 36 (50.7%) had ACS and 35 (49%) had ADHF. Overall in-hospital mortality was 5.5% (n = 16). Multivariate logistic regression identified the following independent predictors of AKI in male patients with ACS: previous myocardial infarction at age >65 years (OR 5.967, 95% CI 1.16–30.47, p = 0.03), chronic kidney disease (OR 3.72, 95% CI 1.31–16.61, p = 0.01), and decreased hemoglobin levels (OR 0.684, 95% CI 0.53–0.88, p = 0.03). No variable was identified as an independent risk factor in ADHF patients. Kaplan-Meier survival curves indicated that patients with ACS plus AKI had significantly higher in-hospital mortality (log rank = 0.007).
Conclusion
Acute CRS (type 1 CRS) is more frequent in patients with ADHF and can be considered multifactorial. Although CRS is less frequent in ACS patients, it is associated with longer hospital stay and with higher in-hospital mortality. The heart-kidney interaction should be managed collaboratively between cardiologists and nephrologists to increase our knowledge and enhance clinical approaches.
doi:10.1159/000337714
PMCID: PMC3433012  PMID: 22969772
Acute renal failure; Chronic kidney disease; Statistics and epidemiology; Acute cardiorenal syndrome; Acute kidney injury; Acute coronary syndrome; Acute decompensated heart failure
6.  Influence of acute kidney injury on short- and long-term outcomes in patients undergoing cardiac surgery: risk factors and prognostic value of a modified RIFLE classification 
Critical Care  2013;17(6):R293.
Introduction
The development of acute kidney injury (AKI) is associated with poor outcome. The modified RIFLE (risk, injury, failure, loss of kidney function, and end-stage renal failure) classification for AKI, which classifies patients with renal replacement therapy needs according to RIFLE failure class, improves the predictive value of AKI in patients undergoing cardiac surgery. Our aim was to assess risk factors for post-operative AKI and the impact of renal function on short- and long-term survival among all AKI subgroups using the modified RIFLE classification.
Methods
We prospectively studied 2,940 consecutive cardiosurgical patients between January 2004 and July 2009. AKI was defined according to the modified RIFLE system. Pre-operative, operative and post-operative variables usually measured on and during admission, which included main outcomes, were recorded together with cardiac surgery scores and ICU scores. These data were evaluated for association with AKI and staging in the different RIFLE groups by means of multivariable analyses. Survival was analyzed via Kaplan-Meier and a risk-adjusted Cox proportional hazards regression model. A complete follow-up (mean 6.9 ± 4.3 years) was performed in 2,840 patients up to April 2013.
Results
Of those patients studied, 14% (n = 409) were diagnosed with AKI. We identified one intra-operative (higher cardiopulmonary bypass time) and two post-operative (a longer need for vasoactive drugs and higher arterial lactate 24 hours after admission) predictors of AKI. The worst outcomes, including in-hospital mortality, were associated with the worst RIFLE class. Kaplan-Meier analysis showed survival of 74.9% in the RIFLE risk group, 42.9% in the RIFLE injury group and 22.3% in the RIFLE failure group (P <0.001). Classification at RIFLE injury (Hazard ratio (HR) = 2.347, 95% confidence interval (CI) 1.122 to 4.907, P = 0.023) and RIFLE failure (HR = 3.093, 95% CI 1.460 to 6.550, P = 0.003) were independent predictors for long-term patient mortality.
Conclusions
AKI development after cardiac surgery is associated mainly with post-operative variables, which ultimately could lead to a worst RIFLE class. Staging at the RIFLE injury and RIFLE failure class is associated with higher short- and long-term mortality in our population.
doi:10.1186/cc13159
PMCID: PMC4056889  PMID: 24330769
7.  Long-Term Survival and Dialysis Dependency Following Acute Kidney Injury in Intensive Care: Extended Follow-up of a Randomized Controlled Trial 
PLoS Medicine  2014;11(2):e1001601.
Martin Gallagher and colleagues examine the long-term outcomes of renal replacement therapy (RRT) dosing in patients with acute kidney injury randomized to normal vs. augmented RRT.
Please see later in the article for the Editors' Summary
Background
The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.
Methods and Findings
We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0–48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96–1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63–2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.
Conclusions
Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.
Trial registration
www.ClinicalTrials.gov NCT00221013
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Throughout life, the kidneys perform the essential task of filtering waste products (from the normal breakdown of tissues and from food) and excess water from the blood to make urine. Chronic kidney disease (caused, for example, by diabetes) gradually destroys the kidneys' filtration units (the nephrons), eventually leading to life-threatening end-stage kidney disease. However, the kidneys can also stop working suddenly because of injury, infection, or poisoning. Acute kidney injury (AKI) is much more common than end-stage kidney disease and its incidence is increasing worldwide. In the US, for example, the number of hospitalizations that included an AKI diagnosis rose from 4,000 in 1996 to 23,000 in 2008. Moreover, nearly half of patients with AKI will die shortly after the condition develops. Symptoms of AKI include changes in urination, swollen feet and ankles, and tiredness. Treatments for AKI aim to prevent fluid and waste build up in the body and treat the underlying cause (e.g., severe infection or dehydration) while allowing the kidneys time to recover. In some patients, it is sufficient to limit the fluid intake and to reduce waste build-up by eating a diet that is low in protein, salt, and potassium. Other patients need renal replacement therapy (RRT), life-supporting treatments such as hemodialysis and hemofiltration, two processes that clean the blood by filtering it outside the body.
Why Was This Study Done?
The long-term outcomes of AKI (specifically, death and chronic kidney disease) and the effects of different RRT modalities on these outcomes are unclear. A recent controlled trial that randomly assigned patients with AKI who were managed in intensive care units (ICUs) to receive two different intensities of continuous hemodiafiltration (a combination of hemodialysis and hemofiltration) found no difference in all-cause mortality (death) at 90 days. Here, the researchers extend the follow-up of this trial (the Randomized Evaluation of Normal vs. Augmented Levels of renal replacement therapy [RENAL] study) to investigate longer-term mortality, the variables that predict mortality, treatment with long-term dialysis (an indicator of chronic kidney disease), and functional outcomes in patients with AKI treated with different intensities of continuous RRT.
What Did the Researchers Do and Find?
For the Prolonged Outcomes Study of RENAL (POST-RENAL), the researchers extended the follow-up of the RENAL participants up to 4 years. Over an average follow-up of 43.9 months, 63% of patients in the lower intensity treatment group died compared to 62% of patients in the higher intensity group. Overall, a third of patients who survived to 90 days died during the extended follow-up. Among the survivors to day 90, 5.1% and 5.8% of patients in the lower and higher intensity groups, respectively, were treated with maintenance dialysis during the extended follow-up. Among survivors who consented to analysis, 40% and 44% of patients in the lower and higher intensity groups, respectively, had albuminuria (protein in the urine, an indicator of kidney damage). Patients in both groups had a similar quality life (determined through telephone interviews). Finally, increasing age, APACHE III score (a scoring system that predicts the survival of patients in ICU), and serum creatinine level (an indicator of kidney function) at randomization were all predictors of long-term mortality.
What Do These Findings Mean?
These findings indicate that patients with AKI in ICUs who require RRT have a high long-term mortality. They show that few survivors require maintenance dialysis for chronic kidney disease but that there is a substantial rate of albuminuria among survivors despite relative preservation of kidney function. The findings also suggest that the intensity of RRT has no significant effect on mortality or the need for dialysis. Because these findings were obtained in a randomized controlled trial, they may not be generalizable to other patient populations. Moreover, although data on mortality and maintenance dialysis were available for all the trial participants, clinical and biochemical outcomes were only available for some participants and may not be representative of all the participants. Despite these study limitations, these findings suggest that survivors of AKI may be at a high risk of death or of developing chronic kidney disease. Survivors of AKI are, therefore, at high risk of further illness and long-term albuminuria reduction strategies may offer a therapeutic intervention for this group of patients.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001601.
The US National Kidney and Urologic Diseases Information Clearinghouse provides information about the kidneys and about all aspects of kidney disease and its treatment; the US National Kidney Disease Education Program provides resources to help improve the understanding, detection, and management of kidney disease (in English and Spanish)
The Mayo Clinic provides information for patients about acute kidney injury
Wikipedia has a page on acute kidney injury (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The not-for-profit UK National Kidney Federation provides support and information for patients with kidney disease and for their carers, including a link to a video about acute kidney injury
World Kidney Day, a joint initiative between the International Society of Nephrology and the International Federation of Kidney Foundations (IFKF), aims to raise awareness about kidneys and kidney disease; its website provides information about acute kidney injury
The MedlinePlus Encyclopedia has a pages about acute kidney failure and about renal dialysis
The UK National Institute for Health and Care Excellence (NICE) recently published new guidelines on the treatment of acute kidney injury; a clinical practice guideline for acute kidney injury produced by KDIGO (a not-for-profit organization that aims to improve the care and outcomes of kidney disease patients worldwide through the development and implementation of global clinical practice guidelines) is available; the Acute Kidney Injury app provides a fast and simple way to explore guidelines on the diagnosis, prevention, and management of AKI
doi:10.1371/journal.pmed.1001601
PMCID: PMC3921111  PMID: 24523666
8.  A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients 
Critical Care  2012;16(5):R200.
Introduction
The Risk, Injury, Failure, Loss, and End-Stage Renal Disease (RIFLE) is a consensus-based classification system for diagnosing acute kidney insufficiency (AKI), based on serum creatinine (SCr) and urine output criteria (RIFLESCr+UO). The urine output criteria, however, are frequently discarded and many studies in the literature applied only the SCr criteria (RIFLESCr). We diagnosed AKI using both RIFLE methods and compared the effects on time to AKI diagnosis, AKI incidence and AKI severity.
Methods
This was a prospective observational cohort study during four months in adult critically ill patients admitted to the ICU for at least 48 hours. During the first week patients were scored daily for AKI according to RIFLESCr+UO and RIFLESCr. We assessed urine output hourly and fluid balance daily. The baseline SCr was estimated if a recent pre-ICU admission SCr was unknown. Based on the two RIFLE methods for each patient we determined time to AKI diagnosis (AKI-0) and maximum RIFLE grade.
Results
We studied 260 patients. A pre-ICU admission SCr was available in 101 (39%) patients. The two RIFLE methods resulted in statistically significantly different outcomes for incidence of AKI, diagnosis of AKI for individual patients, distribution of AKI-0 and distribution of the maximum RIFLE grade. Discarding the RIFLE urine criteria for AKI diagnosis significantly underestimated the presence and grade of AKI on admission and during the first ICU week (P < 0,001) and significantly delayed the diagnosis of AKI (P < 0.001). Based on RIFLESCr 45 patients had no AKI on admission but subsequently developed AKI. In 24 of these patients (53%) AKI would have been diagnosed at least one day earlier if the RIFLE urine criteria had been applied. Mortality rate in the AKI population was 38% based on RIFLESCr and 24% based on RIFLESCr+UO (P = 0.02).
Conclusions
The use of RIFLE without the urine criteria significantly underscores the incidence and grade of AKI, significantly delays the diagnosis of AKI and is associated with higher mortality.
doi:10.1186/cc11808
PMCID: PMC3682302  PMID: 23078781
9.  Early acute kidney injury and sepsis: a multicentre evaluation 
Critical Care  2008;12(2):R47.
Introduction
We conducted a study to evaluate the incidence, risk factors and outcomes associated with early acute kidney injury (AKI) in sepsis.
Methods
The study was a retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were collected from 57 intensive care units (ICUs) across Australia. In total, 120,123 patients admitted to ICU for more than 24 hours from 1 January 2000 to 31 December 2005 were included in the analysis. The main outcome measures were clinical and laboratory data and outcomes.
Results
Of 120,123 patients admitted, 33,375 had a sepsis-related diagnosis (27.8%). Among septic patients, 14,039 (42.1%) had concomitant AKI (septic AKI). Sepsis accounted for 32.4% of all patients with AKI. For septic AKI stratified by RIFLE (risk of renal failure, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease) category, 38.5% of patients belonged to the risk category, 38.8% to the injury category and 22.7% to the failure category. Septic AKI patients had greater acuity of illness (P < 0.0001), lower blood pressure (P < 0.0001), higher heart rates (P < 0.0001), worse pulmonary function measures by arterial oxygen tension/fraction of inspired oxygen ratio (P < 0.0001), greater acidaemia (P < 0.0001) and higher white cell counts (P < 0.0001) compared with patients with nonseptic AKI. Septic AKI was also associated with greater severity of AKI (RIFLE category injury or failure) compared with nonseptic AKI. Septic AKI was associated with a significantly higher crude and co-variate adjusted mortality in the ICU (19.8% versus 13.4%; odds ratio 1.60, 95% confidence interval 1.5 to 1.7; P < 0.001) and in hospital (29.7% versus 21.6%; odds ratio 1.53, 95% confidence interval 1.46 to 1.60; P < 0.001) compared with nonseptic AKI. Septic AKI was associated with higher ICU and hospital mortality across all strata of RIFLE categories. Septic AKI patients had longer durations of stay in both ICU and hospital across all strata of RIFLE categories.
Conclusion
Septic AKI is common during the first 24 hours after ICU admission. Patients with septic AKI are generally sicker, with a higher burden of illness, and have greater abnormalities in acute physiology compared with patients with nonseptic AKI. Moreover, septic AKI is independently associated with higher odds of death and longer duration of hospitalization.
doi:10.1186/cc6863
PMCID: PMC2447598  PMID: 18402655
10.  Spectrum of acute kidney injury in critically ill patients: A single center study from South India 
Indian Journal of Nephrology  2014;24(5):280-285.
Acute kidney injury (AKI) is common in intensive care unit (ICU) and carries a high mortality rate. Reliable and comparable data about the clinical spectrum of AKI is necessary for optimizing management. The study was conducted to describe epidemiology, etiology, clinical characteristics and outcome of AKI in critically ill patients without pre-existing renal disease, diagnosed using RIFLE criteria. We retrospectively analyzed data of 500 adult patients admitted to ICU with AKI or who developed AKI in ICU. Patients with pre-existing renal disease, renal transplant recipients were excluded. AKI was predominantly encountered in older males. Diabetes, hypertension, coronary artery disease were the most commonly prevalent comorbidities. Sepsis was the most common cause of AKI, accounting for 38.6% of patients. 24.4% belonged to risk class, 37.0% to injury class, 35.0% to failure class, 3% to loss and 0.6% to ESRD class of the RIFLE criteria. Renal replacement therapy (RRT) was required in 37.2% (n = 186) of patients. About 60% recovered complete renal function. Chronic kidney disease (CKD) was a sequel in 2.4% (n = 12) of patients. Average duration of ICU stay was 5.6 days. Crude mortality rate was 37.6% (n = 188). In critically ill patients without pre-existing renal disease, elderly age, male sex, type 2 diabetes along with a primary diagnosis of sepsis were most commonly associated with AKI. Majority of the patients’ recovered complete renal function.
doi:10.4103/0971-4065.132991
PMCID: PMC4165051  PMID: 25249716
Acute kidney injury; critically ill patients; end stage criteria; failure; India; injury; loss; risk; spectrum
11.  Neutrophil Gelatinase-Associated Lipocalin (NGAL) predicts renal injury in acute decompensated cardiac failure: a prospective observational study 
Background
Acute Decompensated Cardiac Failure (ADCF) is frequently associated with deterioration in renal function. Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We aimed to determine if NGAL measured at admission predicts in-hospital acute kidney injury (AKI) in ADCF.
Methods
A prospective observational study measured NGAL and B-natriuretic peptide (BNP) from patients with ADCF presenting to two tertiary hospitals. Patients received standard care and were followed up daily as inpatients. ADCF was defined by PRIDE score ≥ 6 and AKI by RIFLE criteria.
Results
One hundred and two patients (median age 80, IQR 69-84 years, 52% male) were enrolled. AKI developed in 22 (25%) of 90 for whom outcome data was available. Seven patients died. NGAL was significantly elevated in those who developed AKI versus those who did not (median 130 ng/ml vs 69 ng/ml, p = 0.002). NGAL was also higher in those who died (median 136 ng/ml vs 68 ng/ml, p = 0.005). AKI was significantly associated with risk of death (5/22 (23%) vs 1/68 (1.5%), p = 0.001), but not length of hospital stay. NGAL significantly correlated with admission eGFR but not BNP. For prediction of AKI, NGAL > 89 ng/ml had sensitivity of 68% and specificity of 70% with area under the receiver operator characteristic (ROC) curve of 0.71 (0.58-0.84). After adjustment for baseline renal function, the odds ratio (OR) for AKI was 3.73 (1.26-11.01) if admission NGAL > 89 ng/ml.
Conclusions
Elevated NGAL at admission is associated with in-hospital AKI and mortality in patients with ADCF. However, it has only moderate diagnostic accuracy in this setting.
doi:10.1186/1471-2261-12-8
PMCID: PMC3299625  PMID: 22340728
12.  Long term outcome of acute kidney injury due to leptospirosis? A longitudinal study in Sri Lanka 
BMC Research Notes  2014;7:398.
Background
Leptospirosis is an important zoonotic disease of variable severity and is a common cause of acute kidney injury (AKI) in tropics. However the knowledge on long term renal outcome in leptospirosis is scarce. This study aims to assess the long-term renal outcome of AKI caused by leptospirosis.
Findings
Hospital records of patients who had developed AKI following leptospirosis (Serologically confirmed) presented to two Teaching Hospitals in Kandy district over 3 years from 2007 were studied. A total of 44 patients were included and they had been followed up at least for one year in out patient clinics with regular assessment including renal status. Renal histology was studied in two patients. The primary outcome measure was normalization of renal function at one year. Of the 44 patients, 31 were in the risk and injury stage (Group 1), and the rest of them were in the failure stage (Group 2) under RIFLE criteria. Of group 2 patients, 11 had abnormal renal functions on discharge. Their mean serum creatinine and GFR values on discharge were 392 mmol/l and 20 ml/min/1.73 m2. Other two patients had full renal recovery whilst in the hospital. Nine in the group 2 required renal replacement therapy by means of peritoneal dialysis, intermittent haemodialysis or haemofiltration. Seventeen out of the total had persistently abnormal renal functions on discharge. Of them 13 recovered their renal functions to normal. Four patients (9%) who belonged to group 2, had persistently abnormal renal functions after first year compatible with stage 3 chronic kidney disease (CKD). Renal histology of two patients showed tubulointerstitial lymphocyte infiltrate, tubular atrophy and interstitial fibrosis.
Conclusion
The long term renal outcome of AKI following leptospirosis is satisfactory as only 9% of patients had abnormal renal functions compatible with early stage of CKD. Even among them, advanced CKD or dialysis dependency had not been observed.
doi:10.1186/1756-0500-7-398
PMCID: PMC4080986  PMID: 24964804
Leptospirosis; Acute kidney injury; Chronic kidney disease; Long term renal outcome; Sri Lanka
13.  Chronic Kidney Disease after Acute Kidney Injury: A Systematic Review and Meta-analysis 
Kidney international  2011;81(5):442-448.
Acute kidney injury may increase the risk for chronic kidney disease and end-stage renal disease. In an attempt to summarize the literature and provide more compelling evidence, we conducted a systematic review comparing the risk of CKD, ESRD and death in patients with and without AKI. From electronic databases, web search engines, and bibliographies, 13 cohort studies were selected, evaluating long-term renal outcomes and non-renal outcomes in patients with AKI. The pooled incidence of CKD and ESRD were 25.8/100 person-years and 8.6 per 100 person-years, respectively. Patients with AKI had higher risks of developing CKD (pooled adjusted hazard ratio 8.8, 95% CI 3.1-25.5), ESRD (pooled adjusted HR 3.1, 95% CI 1.9-5.0) and mortality (pooled adjusted HR 2.0, 95% CI 1.3-3.1) than patients without AKI. The relationship between AKI and CKD or ESRD was graded depending on the severity of AKI and the effect size was dampened by decreased baseline glomerular filtration rate. Data were limited, but AKI was also independently associated with the risk for cardiovascular disease and congestive heart failure, but not with hospitalization for stroke or all-cause hospitalizations. Meta-regression did not identify any study level factors that were associated with the risk for CKD or ESRD. Our review identifies AKI as an independent risk factor for CKD, ESRD, and death and other important non-renal outcomes.
doi:10.1038/ki.2011.379
PMCID: PMC3788581  PMID: 22113526
14.  Kidney function decline after a non-dialysis-requiring acute kidney injury is associated with higher long-term mortality in critically ill survivors 
Critical Care  2012;16(4):R123.
Introduction
The adverse consequences of a non-dialysis-requiring acute kidney injury (AKI) are unclear. This study aimed to assess the long-term prognoses for critically ill patients experiencing a non-dialysis-requiring AKI.
Methods
This retrospective observational cohort study investigated non-dialysis-requiring AKI survivors in surgical intensive care units between January 2002 and June 2010. All longitudinal post-discharge serum creatinine measurements and information regarding end-stage renal disease (ESRD) and death were collected. We assessed the long-term outcomes of chronic kidney disease (CKD), ESRD and all-cause mortality beyond discharge.
Results
Of the 922 identified critically ill patients with a non-dialysis-requiring AKI, 634 (68.8%) patients who survived to discharge were enrolled. A total of 207 patients died after a median follow-up of 700.5 days. The median intervals between the onset of the AKI and the composite endpoints "stage 3 CKD or death", "stage 4 CKD or death", "stage 5 CKD or death", and "ESRD or death" were 685, 1319, 1743, and 2048 days, respectively. This finding shows a steady long-term decline in kidney function after discharge. Using the multivariate Cox proportional hazard model, we found that every 1 mL/min/1.73 m2 decrease from baseline estimated glomerular filtration rate (eGFR) of individuals who progressed to stage 3, 4, and 5 CKD increased the risks of long-term mortality by 0.7%, 2.3%, and 4.1%, respectively (all p < 0.05). This result indicates that the mortality risk increased significantly in a graded manner as kidney function declined from the baseline eGFR to advanced stages of CKD during the follow-up period.
Conclusions
In critically ill patients who survive a non-dialysis-requiring AKI, there is a need for continuous monitoring and kidney function protection beyond discharge.
doi:10.1186/cc11419
PMCID: PMC3580702  PMID: 22789111
15.  Early Acute Kidney Injury Predicts Progressive Renal Dysfunction and Higher Mortality in Severely Burned Adults 
The incidence and prognosis of acute kidney injury (AKI) developing during acute resuscitation have not been well characterized in burn patients. The recently developed Risk, Injury, Failure, Loss, and End-stage (RIFLE) classification provides a stringent stratification of AKI severity and can allow for the study of AKI after burn injury. We hypothesized that AKI frequently develops early during resuscitation and is associated with poor outcomes in severely burned patients. We conducted a retrospective review of patients enrolled in the prospective observational multicenter study “Inflammation and the Host Response to Injury.” A RIFLE score was calculated for all patients at 24 hours and throughout hospitalization. Univariate and multivariate analyses were performed to distinguish the impact of early AKI on progressive renal dysfunction, need for renal replacement therapy, and hospital mortality. A total of 221 adult burn patients were included, with a mean TBSA burn of 42%. Crystalloid resuscitation averaged 5.2 ml/kg/%TBSA, with urine output of 1.0 ± 0.6 ml/kg/hr at 24 hours. Sixty-two patients met criteria for AKI at 24 hours: 23 patients (10%) classified as risk, 32 patients (15%) as injury, and 7 (3%) as failure. After adjusting for age, TBSA, inhalation injury, and nonrenal Acute Physiology and Chronic Health Evaluation II ≥20, early AKI was associated with an adjusted odds ratio 2.9 for death (95% CI 1.1–7.5, P = .03). In this cohort of severely burned patients, 28% of patients developed AKI during acute resuscitation. AKI was not always transient, with 29% developing progressive renal deterioration by RIFLE criteria. Early AKI was associated with early multiple organ dysfunction and higher mortality risk. Better understanding of how early AKI develops and which patients are at risk for progressive renal dysfunction may lead to improved outcomes.
doi:10.1097/BCR.0b013e3181cb8c87
PMCID: PMC3045668  PMID: 20061841
16.  Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial 
Critical Care  2014;18(3):R134.
Introduction
Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics.
Methods
Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge.
Results
A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m2P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04).
Conclusions
In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months.
Trial registration
ClinicalTrials.gov NCT01441245. Registered 23 September 2011.
doi:10.1186/cc13952
PMCID: PMC4227080  PMID: 24974232
17.  Correlation between the AKI classification and outcome 
Critical Care  2008;12(6):R144.
Introduction
The Acute Kidney Injury Network proposed a new classification for acute kidney injury (AKI) distinguishing between three stages. We applied the criteria to a large intensive care unit (ICU) population and evaluated the impact of AKI in the context of other risk factors.
Methods
Using the Riyadh Intensive Care Program database, we applied the AKI classification to 22,303 adult patients admitted to 22 ICUs in the UK and Germany between 1989 and 1999, who stayed in the ICU for 24 hours or longer and did not have end-stage dialysis dependent renal failure.
Results
Of the patients, 7898 (35.4%) fulfilled the criteria for AKI (19.1% had AKI I 3.8% had AKI II and 12.5% had AKI III). Mortality in the ICU was 10.7% in patients with no AKI, 20.1% in AKI I, 25.9% in AKI II and 49.6% in AKI III. Multivariate analysis confirmed that AKI III, but not AKI I and AKI II, were independently associated with ICU mortality (odds ratio (OR) = 2.27). Other independent risk factors for ICU mortality were age (OR = 1.03), sequential organ failure assessment (SOFA) score on admission to the ICU (OR = 1.11), pre-existing end-stage chronic health (OR = 1.65), emergency surgery (OR = 2.33), mechanical ventilation (OR = 2.83), maximum number of failed organ systems (OR = 2.80) and non-surgical admission (OR = 3.57). Cardiac surgery, AKI I and renal replacement therapy were associated with a reduced risk of dying in the ICU. AKI II was not an independent risk factor for ICU mortality. Without renal replacement therapy as a criterion, 21% of patients classified as AKI III would have been classified as AKI II or AKI I. Renal replacement therapy as a criterion for AKI III may inadvertently diminish the predictive power of the classification.
Conclusions
The proposed AKI classification correlated with ICU outcome but only AKI III was an independent risk factor for ICU mortality. The use of renal replacement therapy as a criterion for AKI III may have a confounding effect on the predictive power of the classification system as a whole.
doi:10.1186/cc7123
PMCID: PMC2646305  PMID: 19019254
18.  Acute kidney injury in septua- and octogenarians after cardiac surgery 
Background
An increasing number of septua- and octogenarians undergo cardiac surgery. Acute kidney injury (AKI) still is a frequent complication after surgery. We examined the incidence of AKI and its impact on 30-day mortality.
Methods
A retrospective study between 01/2006 and 08/2009 with 299 octogenarians, who were matched for gender and surgical procedure to 299 septuagenarians at a university hospital. Primary endpoint was AKI after surgery as proposed by the RIFLE definition (Risk, Injury, Failure, Loss, End-stage kidney disease). Secondary endpoint was 30-day mortality. Perioperative mortality was predicted with the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE).
Results
Octogenarians significantly had a mean higher logistic EuroSCORE compared to septuagenarians (13.2% versus 8.5%; p < 0.001) and a higher proportion of patients with an estimated glomerular filtration rate (eGFR) < 60 ml × min-1 × 1.73 m-2. In contrast, septuagenarians showed a slightly higher median body mass index (28 kg × m-2 versus 26 kg × m-2) and were more frequently active smoker at time of surgery (6.4% versus 1.6%, p < 0.001). Acute kidney injury and failure developed in 21.7% of septuagenarians and in 21.4% of octogenarians, whereas more than 30% of patients were at risk for AKI (30% and 36.3%, respectively). Greater degrees of AKI were associated with a stepwise increase in risk for death, renal replacement therapy and prolonged stays at the intensive care unit and at the hospital in both age groups, but without differences between them. Overall 30-day mortality was 6% in septuagenarians and 7.7% in octogenarians (p = 0.52).
The RIFLE classification provided accurate risk assessment for 30-day mortality and fair discriminatory power.
Conclusions
The RIFLE criteria allow identifying patients with AKI after cardiac surgery. The high incidence of AKI in septua- and octogenarians after cardiac surgery should prompt the use of RIFLE criteria to identify patients at risk and should stimulate institutional measures that target AKI as a quality improvement initiative for patients at advanced age.
doi:10.1186/1471-2261-11-52
PMCID: PMC3163622  PMID: 21835003
Acute kidney injury; cardiac surgery; extracorporeal circulation; mortality; septuagenarians; octogenarians
19.  A comparison of different diagnostic criteria of acute kidney injury in critically ill patients 
Critical Care  2014;18(4):R144.
Introduction
Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) proposed a new definition and classification of acute kidney injury (AKI) on the basis of the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage renal failure) and AKIN (Acute Kidney Injury Network) criteria, but comparisons of the three criteria in critically ill patients are rare.
Methods
We prospectively analyzed a clinical database of 3,107 adult patients who were consecutively admitted to one of 30 intensive care units of 28 tertiary hospitals in Beijing from 1 March to 31 August 2012. AKI was defined by the RIFLE, AKIN, and KDIGO criteria. Receiver operating curves were used to compare the predictive ability for mortality, and logistic regression analysis was used for the calculation of odds ratios and 95% confidence intervals.
Results
The rates of incidence of AKI using the RIFLE, AKIN, and KDIGO criteria were 46.9%, 38.4%, and 51%, respectively. KDIGO identified more patients than did RIFLE (51% versus 46.9%, P = 0.001) and AKIN (51% versus 38.4%, P <0.001). Compared with patients without AKI, in-hospital mortality was significantly higher for those diagnosed as AKI by using the RIFLE (27.8% versus 7%, P <0.001), AKIN (32.2% versus 7.1%, P <0.001), and KDIGO (27.4% versus 5.6%, P <0.001) criteria, respectively. There was no difference in AKI-related mortality between RIFLE and KDIGO (27.8% versus 27.4%, P = 0.815), but there was significant difference between AKIN and KDIGO (32.2% versus 27.4%, P = 0.006). The areas under the receiver operator characteristic curve for in-hospital mortality were 0.738 (P <0.001) for RIFLE, 0.746 (P <0.001) for AKIN, and 0.757 (P <0.001) for KDIGO. KDIGO was more predictive than RIFLE for in-hospital mortality (P <0.001), but there was no difference between KDIGO and AKIN (P = 0.12).
Conclusions
A higher incidence of AKI was diagnosed according to KDIGO criteria. Patients diagnosed as AKI had a significantly higher in-hospital mortality than non-AKI patients, no matter which criteria were used. Compared with the RIFLE criteria, KDIGO was more predictive for in-hospital mortality, but there was no significant difference between AKIN and KDIGO.
doi:10.1186/cc13977
PMCID: PMC4227114  PMID: 25005361
20.  Novel Urinary Biomarkers in Detecting Acute Kidney Injury, Persistent Renal Impairment and All-cause Mortality following Decongestive Therapy in Acute Decompensated Heart Failure 
Journal of cardiac failure  2013;19(9):621-628.
Background
New urinary biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) are proposed to allow a more reliable early diagnosis and prognosis of acute kidney injury (AKI) in acute decompensated heart failure (ADHF). Our aim was to compare the predictive value of urinary NGAL, KIM-1 and IL-18 for the occurrence of AKI, persistent renal impairment and mortality in ADHF.
Methods and Results
Eighty-three patients admitted for ADHF were analyzed. Urinary creatinine (Cr), NGAL, KIM-1 and IL-18 were measured at baseline. Serum Cr was measured daily during the next 4 days and again at outpatient follow-up after 6 months. Mortality data were prospectively collected. Urinary NGAL, KIM-1 and IL-18 were modestly correlated with each other (Spearman's ρ≤0.61) and poorly correlated to estimated glomerular filtration rate (eGFR; Spearman's ρ≤0.28). None predicted AKI defined as a 25% decrease in eGFR during index hospitalization, but urinary IL-18/Cr was the strongest predictor of persistently elevated serum Cr≥0.3 mg/dL after 6 months compared to baseline (AUC=0.674; p=0.013). Urinary IL-18 was also associated with all-cause mortality (HR 1.48, 95%CI 1.16–1.87; p=0.001).
Conclusions
Like urinary NGAL, urinary KIM-1 and IL-18 are relatively modest predictors of AKI in ADHF. Among these novel renal biomarkers examined, further investigations regarding the prognostic value of urinary IL-18 are warranted.
doi:10.1016/j.cardfail.2013.07.004
PMCID: PMC3781948  PMID: 24054338
Acute decompensated heart failure; acute kidney injury; biomarkers; outcome
21.  Lack of significant renal tubular injury despite acute kidney injury in acute decompensated heart failure 
European Journal of Heart Failure  2012;14(6):597-604.
Aims
Acute kidney injury (AKI) is a strong predictor of adverse events with an incompletely understood pathophysiology. Neutrophil gelatinase-associated lipocalin (NGAL) is proposed as an early marker of renal tubular injury. Our aim is to determine whether AKI during treatment of acute decompensated heart failure (ADHF) is accompanied by renal tubular injury.
Methods and results
Urinary NGAL (uNGAL) and urinary creatinine (uCreat) levels were measured in 141 consecutive patients hospitalized for ADHF and followed for 180 days for death or re-hospitalization. AKI was defined as a rise in serum creatinine ≥0.3 mg/dl in a 48 h period. Median uNGAL/uCreat levels on Day 1 (baseline) were similar between patients who did and did not develop AKI [22.8 (12.5–106.8) μg/g vs. 20.6 (12.4–52.0) μg/g, P = 0.55]. On Day 2 and beyond, the difference between the AKI and no AKI cohorts increased, but was only significant on Day 3 [36.2 (21.7–131.8) μg/g vs. 29.4 (11.4–54.6) μg/g, P = 0.02]. The area under the receiver operating characteristic curve for Day 2 uNGAL/uCreat (≥ or <32 µg/g) to predict AKI was 0.61. There was no difference in diuretic response between ‘uNGAL/uCreat + ’ (≥ 27 µg/g) and ‘uNGAL/uCreat–’ (<27 µg/g) patients. However ‘uNGAL/uCreat + ’ patients had more adverse events after 180 days (66% vs. 52%, P = 0.02).
Conclusions
In patients with ADHF who develop AKI following diuretic therapy, a minor rise in uNGAL precedes AKI. However, the degree of renal tubular insult was much lower than that observed in other forms of AKI.
doi:10.1093/eurjhf/hfs039
PMCID: PMC3359861  PMID: 22505396
Acute decompensated heart failure; Cardio-renal syndrome; Diuretics; NGAL; Tubular injury
22.  Post Cardiac Surgery Acute Kidney Injury: A Woebegone Status Rejuvenated by the Novel Biomarkers 
Nephro-urology Monthly  2014;6(4):e19598.
Background:
Acute kidney injury (AKI) is common after cardiac surgery, the incidence varying between 7.7% and 28.1%. It significantly increases morbidity and mortality. Creatinine considerably delays the diagnosis with its own attended demerits. Novel urinary biomarkers are emerging which help in rapid diagnosis thus reducing the morbidity and mortality. Biomarkers of our study were neutrophil gelatinase-associated lipocalin (NGAL) and Interleukin-18 (IL-18).
Objectives:
To find out the incidence of AKI in post-cardiac surgery patients in our hospital, the ability of the two biomarkers in early diagnosis in predicting the severity of AKI based on RIFLE’s criteria and their ability to discriminate pre-renal from intrinsic AKI.
Patients and Methods:
One-hundred patients who underwent cardiac surgery were selected. Midstream urine samples were collected at 3 time intervals (baseline before surgery, 24 hours and 7 days after surgery). Biomarkers were measured by ELISA using BIORAD processors. Fractional excretion of sodium and urea were used to discriminate pre-renal from intrinsic AKI.
Results:
Out of 100 patients, 31 had AKI, 11 being pre-renal and 20 intrinsic AKI. Four patients required renal replacement therapy (12.9% among AKI cases and 4% in the overall study cohort). Four among 31 expired in intensive care unit. Identifiable risk factors for AKI included insulin requiring diabetes mellitus, chronic obstructive pulmonary disease, increased cardio-pulmonary bypass time, combined valvular surgery and coronary artery bypass grafting, employment of intra-aortic balloon counter pulsation, left main coronary artery occlusion and an ejection fraction of < 40%. NGAL was extremely sensitive (area under curve-0.96) in detecting intrinsic AKI at 24 hours followed by IL-18 ratio with an area under curve of 0.89. Creatinine at 24 hours was able to detect only 31.6% of intrinsic AKI. None of the pre-renal cases showed rise in the urinary biomarker levels. Patients with higher stages of AKI had higher levels of both biomarkers than those at lower stages.
Conclusions:
NGAL and IL-18 obviated the disadvantages of creatinine. They were efficient in early detection of AKI, in differentiating pre-renal from intrinsic AKI and in predicting the severity of AKI reliably in post-cardiac surgery patients.
doi:10.5812/numonthly.19598
PMCID: PMC4109123  PMID: 25068144
Acute Kidney Injury; NGAL Protein; Interleukin-18
23.  Severe Acute Kidney Injury According to the RIFLE Criteria Affects Mortality in Lung Transplantation 
Background
The RIFLE criteria (Risk, Injury, Failure, Loss, End stage) are new consensus definitions for acute kidney injury (AKI) associated with increased mortality, however they have not been applied in lung transplantation (LTx). Using the RIFLE criteria we examined the impact of AKI on outcomes and cost in LTx.
Methods and Materials
We retrospectively reviewed all LTx patients at our institution since the lung allocation score (LAS) system (5/2005–8/2010). Using the Modification of Diet in Renal Disease (MDRD) formula, we assigned appropriate RIFLE class (R, I, F) comparing baseline creatinine to peak levels in first 7 days post-op. Generalized linear models assessed the effect of AKI on in-hospital and 1-year (yr) mortality. The financial impact of AKI was examined with hospital charges.
Results
106 LTx were performed during the study. Excluding patients bridged to LTx with ECMO, 84(86%) lived 1-yr. Median LAS was 37.1(IQR34.1-45.2). 39(36.7%) were RIFLE-I or F, and 14(13.2%) required renal replacement therapy (RRT). After adjusting for LAS, RIFLE-F had an increased relative rate (RR) of inhospital mortality (RR=4.76, 95% CI 1.65–13.7, p=0.004) and 1-yr mortality (RR=3.17, 95% CI 1.55–6.49, p=0.002). RIFLE-R and I were not associated with higher in-hospital or 1-yr mortality. Post-op RRT was associated with increased in-hospital (RR=28.2, 95% CI 6.18–128.1, p<0.001) and 1-yr mortality (RR=4.97, 95% CI 1.54–16.0, p<0.001). AKI patients had higher median hospital charges (AKI:$168,146 vs no AKI:$143,551, p=0.02).
Conclusions
This is the first study to show high rates of AKI using the new RIFLE criteria in LTx. RIFLE-F is associated with higher in-hospital mortality and 1-yr mortality. Less severe degrees of AKI are not associated with increased mortality. The financial burden associated with AKI is significant.
doi:10.1016/j.healun.2011.04.013
PMCID: PMC3185168  PMID: 21620737
Lung Transplantation; Acute Kidney Injury; RIFLE criteria
24.  Laboratory Test Surveillance following Acute Kidney Injury 
PLoS ONE  2014;9(8):e103746.
Background
Patients with hospitalized acute kidney injury (AKI) are at increased risk for accelerated loss of kidney function, morbidity, and mortality. We sought to inform efforts at improving post-AKI outcomes by describing the receipt of renal-specific laboratory test surveillance among a large high-risk cohort.
Methods
We acquired clinical data from the Electronic health record (EHR) of 5 Veterans Affairs (VA) hospitals to identify patients hospitalized with AKI from January 1st, 2002 to December 31st, 2009, and followed these patients for 1 year or until death, enrollment in palliative care, or improvement in renal function to estimated GFR (eGFR) ≥60 L/min/1.73 m2. Using demographic data, administrative codes, and laboratory test data, we evaluated the receipt and timing of outpatient testing for serum concentrations of creatinine and any as well as quantitative proteinuria recommended for CKD risk stratification. Additionally, we reported the rate of phosphorus and parathyroid hormone (PTH) monitoring recommended for chronic kidney disease (CKD) patients.
Results
A total of 10,955 patients admitted with AKI were discharged with an eGFR<60 mL/min/1.73 m2. During outpatient follow-up at 90 and 365 days, respectively, creatinine was measured on 69% and 85% of patients, quantitative proteinuria was measured on 6% and 12% of patients, PTH or phosphorus was measured on 10% and 15% of patients.
Conclusions
Measurement of creatinine was common among all patients following AKI. However, patients with AKI were infrequently monitored with assessments of quantitative proteinuria or mineral metabolism disorder, even for patients with baseline kidney disease.
doi:10.1371/journal.pone.0103746
PMCID: PMC4130516  PMID: 25117447
25.  Renal Function at Hospital Admission and Mortality Due to Acute Kidney Injury after Myocardial Infarction 
PLoS ONE  2012;7(4):e35496.
Background
The role of an impaired estimated glomerular filtration rate (eGFR) at hospital admission in the outcome of acute kidney injury (AKI) after acute myocardial infarction (AMI) has been underreported. The aim of this study was to assess the influence of an admission eGFR<60 mL/min/1.73 m2 on the incidence and early and late mortality of AMI-associated AKI.
Methods
A prospective study of 828 AMI patients was performed. AKI was defined as a serum creatinine increase of ≥50% from the time of admission (RIFLE criteria) in the first 7 days of hospitalization. Patients were divided into subgroups according to their eGFR upon hospital admission (MDRD formula, mL/min/1.73 m2) and the development of AKI: eGFR≥60 without AKI, eGFR<60 without AKI, eGFR≥60 with AKI and eGFR<60 with AKI.
Results
Overall, 14.6% of the patients in this study developed AKI. The admission eGFR had no impact on the incidence of AKI. However, the admission eGFR was associated with the outcome of AMI-associated AKI. The adjusted hazard ratios (AHR, Cox multivariate analysis) for 30-day mortality were 2.00 (95% CI 1.11–3.61) for eGFR<60 without AKI, 4.76 (95% CI 2.45–9.26) for eGFR≥60 with AKI and 6.27 (95% CI 3.20–12.29) for eGFR<60 with AKI. Only an admission eGFR of <60 with AKI was significantly associated with a 30-day to 1-year mortality hazard (AHR 3.05, 95% CI 1.50–6.19).
Conclusions
AKI development was associated with an increased early mortality hazard in AMI patients with either preserved or impaired admission eGFR. Only the association of impaired admission eGFR and AKI was associated with an increased hazard for late mortality among these patients.
doi:10.1371/journal.pone.0035496
PMCID: PMC3335121  PMID: 22539974

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