Comparison of Diagnostic Criteria for Acute Kidney Injury in Cardiac Surgery

Background

There is considerable controversy regarding the diagnosis of Acute Kidney Injury (AKI), and there are over 30 different definitions.

Objective

To evaluate the incidence and risk factors for the development of AKI following cardiac surgery according to the RIFLE, AKIN and KDIGO criteria, and compare the prognostic power of these criteria.

Methods

Cross-sectional study that included 321 consecutive patients (median age 62 [53-71] years; 140 men) undergoing cardiac surgery between June 2011 and January 2012. The patients were followed for up to 30 days, for a composite outcome (mortality, need for dialysis and extended hospitalization).

Results

The incidence of AKI ranged from 15% - 51%, accordingly to the diagnostic criterion adopted. While age was associated with risk of AKI in the three criteria, there were variations in the remaining risk factors. During follow-up, 89 patients developed the outcome and all criteria were associated with increased risk in the univariate Cox analysis and after adjustment for age, gender, diabetes, and type of surgery. However, after further adjustment for extracorporeal circulation and the presence of low cardiac output, only AKI diagnosed by the KDIGO criterion maintained this significant association (HR= 1.89 [95% CI: 1.18 - 3.06]).

Conclusion

The incidence and risk factors for AKI after cardiac surgery vary significantly according to the diagnostic criteria used. In our analysis, the KDIGO criterion was superior to AKIN and RIFLE with regard its prognostic power.     

AKI in Hospitalized Children: Comparing the pRIFLE,AKIN, and KDIGO Definitions

Background and objectives

Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.

Design, setting, participants, & measurements

Observational, electronic medical record–enabled study of 14,795 hospitalizations at the Lucile Packard Children’s Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov–Smirnov tests, respectively.

Results

AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%–1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.

Conclusions

Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.     

Urinary calprotectin and the distinction between prerenal and intrinsic acute kidney injury

Summary

Background and objectives

To date there is no reliable marker for the differentiation of prerenal and intrinsic acute kidney injury (AKI). We investigated whether urinary calprotectin, a mediator protein of the innate immune system, may serve as a diagnostic marker in AKI.

Design, setting, participants, & measurements

This was a cross-sectional study with 101 subjects including 86 patients with AKI (34 prerenal, 52 intrinsic including 23 patients with urinary tract infection) and 15 healthy controls. Assessment of urinary calprotectin concentration was by ELISA and immunohistochemistry of kidney biopsy specimens using a calprotectin antibody. Inclusion criteria were: admission to hospital for AKI stage 1 to 3 (Acute Kidney Injury Network); exclusion criteria were: prior renal transplantation and obstructive uropathy.

Results

Median urinary calprotectin was 60.7 times higher in intrinsic AKI (1692 ng/ml) than in prerenal AKI (28 ng/ml, p <0.01). Urinary calprotectin in prerenal disease was not significantly different from healthy controls (45 ng/ml, p = 0.25). Receiver operating curve curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.97) in predicting intrinsic AKI. A cutoff level of 300 ng/ml provided a sensitivity of 92.3% and a specificity of 97.1%. Calculating urinary calprotectin/creatinine ratios did not lead to a further increase of accuracy. Immunostainings of kidney biopsies were positive for calprotectin in intrinsic AKI and negative in prerenal AKI.

Conclusions

Accuracy of urinary calprotectin in the differential diagnosis of AKI is high. Whereas calprotectin levels in prerenal disease are comparable with healthy controls, intrinsic AKI leads to highly increased calprotectin concentrations.     

Derivation of Urine Output Thresholds That Identify a Very High Risk of AKI in Patients with Septic Shock

Background and objectives

To promote early detection of AKI, recently proposed pretest probability models combine sub–Kidney Disease Improving Global Outcomes (KDIGO) AKI criteria with baseline AKI risk. The primary objective of this study was to determine sub-KDIGO thresholds that identify patients with septic shock at highest risk for AKI.

Design, setting, participants, & measurements

This was a retrospective analysis of 390 adult patients admitted to the medical intensive care unit (ICU) of a tertiary, academic medical center with septic shock between January 2008 and December 2010. Hourly urine output was collected from the time of septic shock recognition (hour 0) to hour 96, urine catheter removal, or ICU discharge (whichever occurred first). All available serum creatinine (SCr) measurements were collected until hour 96. The AKI pretest probability model was assessed during the first 12 hours of resuscitation and included the initial episode of oliguria, increase from baseline to peak SCr level, and Acute Physiology and Chronic Health Evaluation (APACHE) III score in a multivariable receiver-operator characteristic (ROC) analysis. The primary outcome was the incidence of stage II or III (stage II+) AKI defined by KDIGO criteria. Secondary outcomes included the need for RRT and 28-day mortality.

Results

Ninety-eight (25%) patients developed stage II+ AKI after septic shock recognition. APACHE III score and increase in SCr level in the first 12 hours were not statistically associated with stage II+ AKI in multivariable ROC analysis. Consecutive oliguria for 3 hours had fair predictive ability for achieving stage II+ AKI criteria (area under ROC curve, 0.73; 95% confidence interval [95% CI], 0.68 to 0.78), and oliguria for 5 hours demonstrated optimal accuracy (82%; 95% CI, 79% to 86%).

Conclusions

Three to 5 hours of consecutive oliguria in patients with septic shock may provide a valuable measure of AKI risk. Further validation to support this finding is needed.     

Performance and Limitations of Administrative Data in the Identification of AKI

Background and objectives

Billing codes are frequently used to identify AKI events in epidemiologic research. The goals of this study were to validate billing code–identified AKI against the current AKI consensus definition and to ascertain whether sensitivity and specificity vary by patient characteristic or over time.

Design, setting, participants, & measurements

The study population included 10,056 Atherosclerosis Risk in Communities study participants hospitalized between 1996 and 2008. Billing code–identified AKI was compared with the 2012 Kidney Disease Improving Global Outcomes (KDIGO) creatinine-based criteria (AKI_cr) and an approximation of the 2012 KDIGO creatinine- and urine output–based criteria (AKI_{cr_uop}) in a subset with available outpatient data. Sensitivity and specificity of billing code–identified AKI were evaluated over time and according to patient age, race, sex, diabetes status, and CKD status in 546 charts selected for review, with estimates adjusted for sampling technique.

Results

A total of 34,179 hospitalizations were identified; 1353 had a billing code for AKI. The sensitivity of billing code–identified AKI was 17.2% (95% confidence interval [95% CI], 13.2% to 21.2%) compared with AKI_cr (n=1970 hospitalizations) and 11.7% (95% CI, 8.8% to 14.5%) compared with AKI_{cr_uop} (n=1839 hospitalizations). Specificity was >98% in both cases. Sensitivity was significantly higher in the more recent time period (2002–2008) and among participants aged 65 years and older. Billing code–identified AKI captured a more severe spectrum of disease than did AKI_cr and AKI_{cr_uop}, with a larger proportion of patients with stage 3 AKI (34.9%, 19.7%, and 11.5%, respectively) and higher in-hospital mortality (41.2%, 18.7%, and 12.8%, respectively).

Conclusions

The use of billing codes to identify AKI has low sensitivity compared with the current KDIGO consensus definition, especially when the urine output criterion is included, and results in the identification of a more severe phenotype. Epidemiologic studies using billing codes may benefit from a high specificity, but the variation in sensitivity may result in bias, particularly when trends over time are the outcome of interest.     

Risk factors for acute kidney injury in overweight patients with acute type A aortic dissection: a retrospective study

Background

To identify risk factors for acute kidney injury (AKI) in overweight patients who underwent surgery for acute type A aortic dissection (TAAD).

Methods

A retrospective study including 108 consecutive overweight patients [body mass index (BMI) ≥24] between December 2009 and April 2013 in Beijing Anzhen Hospital has been performed. AKI was defined by Acute Kidney Injury Network (AKIN) criteria, which is based on serum creatinine (sCr) or urine output.

Results

The mean age of the patients was 43.69±9.66 years. Seventy-two patients (66.7%) developed AKI during the postoperative period. A logistic regression analysis was performed to identify two independent risk factors for AKI: elevated preoperative sCr level and 72-h drainage volume. Renal replacement therapy (RRT) was required in 15 patients (13.9%). The overall postoperative mortality rate was 7.4%, 8.3% in AKI group and 5.6% in non-AKI group. There is no statistically significant difference between the two groups (P=0.32).

Conclusions

A higher incidence of AKI (66.7%) in overweight patients with acute TAAD was confirmed. The logistic regression model identified elevated preoperative sCr level and 72-h drainage volume as independent risk factors for AKI in overweight patients. We should pay more attention to prevent AKI in overweight patients with TAAD.     

Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven Model

Background and objectives

A knowledge of baseline serum creatinine (bSCr) is mandatory for diagnosing and staging AKI. With often missing values, bSCr is estimated by back-calculation using several equations designed for the estimation of GFR, assuming a “true” GFR of 75 ml/min per 1.73 m². Using a data set from a large cardiac surgery cohort, we tested the appropriateness of such an approach and compared estimated and measured bSCr. Moreover, we designed a novel data-driven model (estimated serum creatinine [eSCr]) for estimating bSCr. Finally, we analyzed the extent of AKI and mortality rate misclassifications.

Design, setting, participants, & measurements

Data for 8024 patients (2833 women) in our cardiac surgery center were included from 1997 to 2008. Measured and estimated bSCr were plotted against age for men and women. Patients were classified to AKI stages defined by the Kidney Disease Improving Global Outcomes (KDIGO) group. Results were compared with data from another cardiac surgery center in Zurich, Switzerland.

Results

The Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration formulae describe higher estimated bSCr values in younger patients, but lower values in older patients compared with the measured bSCr values in both centers. The Pittsburgh Linear Three Variables formula correctly describes the increasing bSCr with age, however, it underestimates the overall bSCr level, being in the range of the 25% quantile of the measured values. Our eSCr model estimated measured bSCr best. AKI stage 1 classification using all formulae, including our eSCr model, was incorrect in 53%–80% of patients in Vienna and in 74%–91% in Zurich; AKI severity (according to KDIGO stages) and also mortality were overestimated. Mortality rate was higher among patients falsely classified into higher KDIGO stages by estimated bSCr.

Conclusions

bSCr values back-estimated using currently available eGFR formulae are inaccurate and cannot correctly classify AKI stages. Our model eSCr improves the prediction of AKI but to a still inadequate extent.     

Contrast-Associated AKI and Use of Cardiovascular Medications after Acute Coronary Syndrome

Background and objectives

AKI after coronary angiography is associated with poor long-term outcomes. The relationship between contrast-associated AKI and subsequent use of prognosis-modifying cardiovascular medications is unknown.

Design, setting, participants, & measurements

A cohort study of 5911 participants 66 years of age or older with acute coronary syndrome who received a coronary angiogram in Alberta, Canada was performed between November 1, 2002, and November 30, 2008. AKI was identified according to Kidney Disease Improving Global Outcomes AKI criteria.

Results

In multivariable logistic regression models, compared with participants without AKI, those with stages 1 and 2–3 AKI had lower odds of subsequent use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker within 120 days of hospital discharge (adjusted odds ratio, 0.65; 95% confidence interval, 0.53 to 0.80 and odds ratio, 0.34; 95% confidence interval, 0.23 to 0.48, respectively). Subsequent statin and β-blockers use within 120 days of hospital discharge was significantly lower among those with stages 2–3 AKI (adjusted odds ratio, 0.44; 95% confidence interval, 0.31 to 0.64 and odds ratio, 0.46; 95% confidence interval, 0.31 to 0.66, respectively). These associations were consistently seen in patients with diabetes mellitus, heart failure, low baseline eGFR, and albuminuria; 952 participants died during subsequent follow-up after hospital discharge (mean=3.1 years). The use of each class of cardiovascular medication was associated with lower mortality, including among those who had experienced AKI.

Conclusions

Strategies to optimize the use of cardiac medications in people with AKI after coronary angiography might improve care.     

Acute kidney injury in an internal medicine ward in a Portuguese quaternary hospital

BackgroundThe term acute kidney injury (AKI) was proposed to reflect the wide spectrum of traditional acute renal failure. RIFLE classification stratifies AKI into three classes of severity and two classes of outcome. AKIN classification proposes an improvement regarding RIFLE in the stratification of AKI, while recently published KDIGO guidelines comprise characteristics of both RIFLE and AKIN. There are no published studies on the utility and measure of agreement between classifications in patients admitted to internal medicine wards.MethodsProspective study undertaken in two internal medicine wards in a Portuguese hospital. Patients admitted for a minimum of 72 h, with a diagnosis of AKI or acute-on-chronic kidney disease at admission or during hospitalisation, were included. RIFLE, AKIN and KDIGO criteria were applied for identification of AKI and stratification into risk groups.ResultsSixty-nine patients were included, with a mean age of 79.7 ± 10.0 years and mean GFR of 21.7 ± 8.8 mL/min/1.73 m². Hypovolaemia due to dehydration was the main cause of AKI (53.6%) and, thereby, RIFLE classification identified a higher number of patients as having AKI, compared to AKIN (94.2% vs. 84.1%). Most patients (69.6%) recovered to their baseline renal function, however fifteen patients (21.7%) died, 53.3% presenting more severe kidney disease.ConclusionsOur results demonstrate good concordance and correlation between RIFLE, AKIN and KDIGO criteria for the diagnosis of AKI (p < 0.001 at initial and final assessment). The authors support the need for further improvement of the classification, ultimately through the use of new biomarkers capable of earlier identification of patients at risk.     

AKI in Low-Risk versus High-Risk Patients in Intensive Care

Background and objectives

AKI in critically ill patients is usually part of multiorgan failure. However, nonrenal organ failure may not always precede AKI and patients without evidence of these organ failures may not be at low risk for AKI. This study examined the risk and outcomes associated with AKI in critically ill patients with and without cardiovascular or respiratory organ failures at presentation to the intensive care unit (ICU).

Design, setting, participants, & measurements

A large, academic medical center database, with records from July 2000 through October 2008, was used and the authors identified a low-risk cohort as patients without cardiovascular and respiratory organ failures defined as not receiving vasopressor support or mechanical ventilation within the first 24 hours of ICU admission. AKI was defined using Kidney Disease Improving Global Outcomes criteria. The primary end points were moderate to severe AKI (stages 2–3) and risk-adjusted hospital mortality.

Results

Of 40,152 critically ill patients, 44.9% received neither vasopressors nor mechanical ventilation on ICU day 1. Stages 2–3 AKI occurred less frequently in the low-risk patients versus high-risk patients within 24 hours (14.3% versus 29.1%) and within 1 week (25.7% versus 51.7%) of ICU admission. Patients developing AKI in both risk groups had higher risk of death before hospital discharge. However, the adjusted odds of hospital mortality were greater (odds ratio, 2.99; 95% confidence interval, 2.62 to 3.41) when AKI occurred in low-risk patients compared with those with respiratory or cardiovascular failures (odds ratio, 1.19; 95% confidence interval, 1.09 to 1.3); interaction P<0.001.

Conclusions

Patients admitted to ICU without respiratory or cardiovascular failure have a substantial likelihood of developing AKI. Although survival for low-risk patients is better than for high-risk patients, the relative increase in mortality associated with AKI is actually greater for low-risk patients. Strategies aimed at preventing AKI should not exclude ICU patients without cardiovascular or respiratory organ failures.     

Model to predict mortality in critically ill adults with acute kidney injury

Summary

Background and objectives

Acute kidney injury (AKI) requiring dialysis is associated with high mortality. Most prognostic tools used to describe case complexity and to project patient outcome lack predictive accuracy when applied in patients with AKI. In this study, we developed an AKI-specific predictive model for 60-day mortality and compared the model to the performance of two generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and Chronic Health Evaluation II [APACHE II]) scores, and a disease specific (Cleveland Clinic [CCF]) score.

Design, setting, participants, & measurements

Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study; a multicenter randomized trial of intensive versus less intensive renal support in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 VA- and university-affiliated centers.

Results

The 60-day mortality was 53%. Twenty-one independent predictors of 60-day mortality were identified. The logistic regression model exhibited good discrimination, with an area under the receiver operating characteristic (ROC) curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of 0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and CCF, when applied to our cohort, showed relatively poor discrimination, reflected by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and 0.65 (0.62 to 0.69), respectively.

Conclusions

Our new risk model outperformed existing generic and disease-specific scoring systems in predicting 60-day mortality in critically ill patients with AKI. The current model requires external validation before it can be applied to other patient populations.     

Acute kidney injury in patients with hemorrhagic fever with renal syndrome caused by Hantaan virus: comparative evaluation by RIFLE and AKIN criteria

Acute kidney injury (AKI) is one of the most prominent characteristics of hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus. The present study evaluated the incidence and severity of AKI classified by both the RIFLE and AKIN criteria in 120 HFRS patients at 48 h and 1 week of the patient admission. The agreements between RIFLE and AKIN and RIFLE and AKIN defined by serum creatinine (AKINc and RIFLEc) were examined by Kappa statistics. AKI occurred in 79.2% and 82.5% at 48 h and in 84.2% and 89.2% at 1 week of admission by RIFLE and AKIN criteria, respectively. RIFLE and AKIN showed very good agreement in classifying AKI at 48 h and 1 week of admission (κ?>?0.900). RIFLE and RIFLEc and AKIN and AKINc at 48 h and 1 week of admission had almost perfect agreement (κ?>?0.900). The classifications of RIFLE and RIFLEc and AKIN and AKINc at 48 h and 1 week were in good agreement (κ?>?0.650). AKI classifications by RIFLE and AKIN were associated with mortality, occurrence of complications, and length of hospital stay. We conclude that AKI occurs in nearly 90% of HFRS patients during the disease course. RIFLE and AKIN classify AKI in HFRS with similar sensitivity. RIFLEc and AKINc may be used as alternatives of standard RIFLE and AKIN in the settings of general wards. The AKI classifications defined at 48 h of admission have predictive value for HFRS disease progression and severity.     

Fluid Balance,Diuretic Use,and Mortality in Acute Kidney Injury

Summary

Background and objectives

Management of volume status in patients with acute kidney injury (AKI) is complex, and the role of diuretics is controversial. The primary objective was to elucidate the association between fluid balance, diuretic use, and short-term mortality after AKI in critically ill patients.

Design, setting, participants, & measurements

Using data from the Fluid and Catheter Treatment Trial (FACTT), a multicenter, randomized controlled trial evaluating a conservative versus liberal fluid-management strategy in 1000 patients with acute lung injury (ALI), we evaluated the association of post-renal injury fluid balance and diuretic use with 60-day mortality in patients who developed AKI, as defined by the AKI Network criteria.

Results

306 patients developed AKI in the first 2 study days and were included in our analysis. There were 137 in the fluid-liberal arm and 169 in the fluid-conservative arm (P = 0.04). Baseline characteristics were similar between groups. Post-AKI fluid balance was significantly associated with mortality in both crude and adjusted analysis. Higher post-AKI furosemide doses had a protective effect on mortality but no significant effect after adjustment for post-AKI fluid balance. There was no threshold dose of furosemide above which mortality increased.

Conclusions

A positive fluid balance after AKI was strongly associated with mortality. Post-AKI diuretic therapy was associated with 60-day patient survival in FACTT patients with ALI; this effect may be mediated by fluid balance.     

Plasma Catalytic Iron,AKI, and Death among Critically Ill Patients

Background and objectives

Catalytic iron has been hypothesized to be a key mediator of AKI. However, the association between plasma catalytic iron levels and AKI has not been well studied in humans.

Design, settings, participants, & measurements

A single-center, prospective, nonconsecutive cohort study of 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012 was performed. Plasma catalytic iron, free hemoglobin, and other iron markers were measured on ICU days 1 and 4. The primary end point was in-hospital mortality or AKI requiring RRT. Secondary end points included mortality (assessed during hospitalization, at 30 days, and 1 year) and incident AKI, defined by modified Kidney Disease Improving Global Outcomes criteria.

Results

ICU day 1 plasma catalytic iron levels were higher among patients who reached the primary end point (median, 0.74 µmol/l [interquartile range, 0.31–3.65] versus 0.29 µmol/l [0.22–0.46]; P<0.01). ICU day 1 plasma catalytic iron levels were associated with number of packed red blood cell transfusions before ICU arrival (r_s=0.29; P<0.001) and plasma free hemoglobin levels on ICU day 1 (r_s=0.32; P<0.001). Plasma catalytic iron levels on ICU day 1 were significantly associated with in-hospital mortality or AKI requiring RRT, even after adjusting for age, enrollment eGFR, and number of packed red blood cell transfusions before ICU arrival (13 events; adjusted odds ratio per 1-SD higher ln[catalytic iron], 3.33; 95% confidence interval, 1.79 to 6.20). ICU day 1 plasma catalytic iron levels were also significantly associated with incident AKI, RRT, hospital mortality, and 30-day mortality.

Conclusions

Among critically ill patients, elevated plasma catalytic iron levels on arrival to the ICU are associated with a greater risk of incident AKI, RRT, and hospital mortality.     

Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults

Background and objectives

Comprehensive epidemiologic data on AKI are particularly lacking in Asian countries. This study sought to assess the epidemiology and clinical correlates of AKI among hospitalized adults in China.

Design, setting, participants, & measurements

This was a multicenter retrospective cohort study of 659,945 hospitalized adults from a wide range of clinical settings in nine regional central hospitals across China in 2013. AKI was defined and staged according to Kidney Disease Improving Global Outcomes criteria. The incidence of AKI in the cohort was estimated using a novel two-step approach with adjustment for the frequency of serum creatinine tests and other potential confounders. Risk factor profiles for hospital-acquired (HA) and community-acquired (CA) AKI were examined. The in-hospital outcomes of AKI, including mortality, renal recovery, length of stay, and daily cost, were assessed.

Results

The incidence of CA-AKI and HA-AKI was 2.5% and 9.1%, respectively, giving rise to an overall incidence of 11.6%. Although the risk profiles for CA-AKI and HA-AKI differed, preexisting CKD was a major risk factor for both, contributing to 20% of risk in CA-AKI and 12% of risk in HA-AKI. About 40% of AKI cases were possibly drug-related and 16% may have been induced by Chinese traditional medicines or remedies. The in-hospital mortality of AKI was 8.8%. The risk of in-hospital death was higher among patients with more severe AKI. Preexisting CKD and need for intensive care unit admission were associated with higher death risk in patients at any stage of AKI. Transiency of AKI did not modify the risk of in-hospital death. AKI was associated with longer length of stay and higher daily costs, even after adjustment for confounders.

Conclusion

AKI is common in hospitalized adults in China and is associated with significantly higher in-hospital mortality and resource utilization.     

Utilization of Small Changes in Serum Creatinine with Clinical Risk Factors to Assess the Risk of AKI in Critically lll Adults

Background and objectives

Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patient''s clinical course. We set out to assess the performance of this combination approach.

Design, setting, participants, & measurements

A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1–0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit.

Results

Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P<0.001). The sensitivity of this grouping for severe AKI was 92%, the specificity was 62%, the positive predictive value was 16%, and the negative predictive value was 99%. After adjustment for Sequential Organ Failure Assessment score, serum creatinine, and hazard tier for AKI, early creatinine elevation remained an independent predictor for severe AKI (adjusted relative risk, 12.86; 95% confidence interval, 3.52 to 46.97). Addition of early creatinine elevation to the best clinical model improved prediction of the primary outcome (area under the receiver operating characteristic curve increased from 0.75 to 0.83, P<0.001).

Conclusion

Critically ill patients at high AKI risk, based on the combination of clinical factors and early creatinine elevation, are significantly more likely to develop severe AKI. As initially hypothesized, the high-risk combination group methodology can be used to identify patients at low risk for severe AKI in whom AKI biomarker testing may be expected to have low yield. The high risk combination group methodology could potentially allow clinicians to optimize biomarker use.     

Incorporation of Biomarkers with the Renal Angina Index for Prediction of Severe AKI in Critically Ill Children

Background and objectives

Novel AKI biomarkers carry variable performance for prediction of AKI in patients with heterogeneous illness. Until utility is demonstrated in critically ill patients outside of the cardiopulmonary bypass population, AKI biomarkers are unlikely to gain widespread implementation. Operationalization of an AKI risk stratification methodology, termed renal angina, was recently reported to enhance prediction at the time of intensive care unit admission for persistent severe AKI. The renal angina index (RAI) was developed to provide the clinical context to direct AKI biomarker testing. This study tested the hypothesis that incorporation of AKI biomarkers in patients fulfilling renal angina improves the prediction of persistent severe AKI.

Design, setting, participants, & measurements

In a multicenter study of 214 patients admitted to the pediatric intensive care unit with sepsis, the discrimination of plasma neutrophil gelatinase–associated lipocalin (NGAL), matrix metalloproteinase-8 (MMP-8), and neutrophil elastase-2 (Ela-2) were determined individually and in combination with the RAI for severe AKI. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated.

Results

Individual biomarkers demonstrated marginal discrimination for severe AKI (area under curve [AUC]: NGAL, 0.72; MMP-8, 0.68; Ela-2, 0.72), inferior to prediction by the clinical model of the RAI (AUC=0.80). Incorporation of each biomarker significantly added to the renal angina model AKI prediction (AUC=0.80, increased to 0.84–0.88; P<0.05 for each). The inclusion of each biomarker with the RAI demonstrated NRI (0.512, 0.428, and 0.545 for NGAL, MMP-8, and Ela-2, respectively; all P<0.03) and IDI (0.075 for Ela-2). The inclusion of both Ela-2 and NGAL with RAI demonstrated an NRI of 0.871 (P<0.001) and an IDI of 0.1 (P=0.01).

Conclusions

This study shows that incorporation of AKI biomarkers into the RAI improves discrimination for severe AKI. The RAI optimizes the utility of AKI biomarkers in a heterogeneous, critically ill patient population.     

Subacute Kidney Injury in Hospitalized Patients

Background and objectives

The epidemiology of AKI and CKD has been described. However, the epidemiology of progressively worsening kidney function (subacute kidney injury [s-AKI]) developing over a longer time frame than defined for AKI (7 days), but shorter than defined for CKD (90 days), is completely unknown.

Design, setting, participants, & measurements

This retrospective study used a hospital laboratory and admission database. Adult patients admitted to a teaching hospital in Tokyo, Japan, between April 1, 2008, and October 31, 2011, were included. s-AKI was classified into three grades of severity (mild, moderate, severe) in accordance with the Risk, Injury, and Failure categories of the Risk, Injury, Failure, Risk, Loss, and ESRD classification, but did not use its time frame. Kidney injury (AKI and s-AKI) occurring during each hospital stay was identified, and logistic regression analysis was performed to assess their effect on hospital mortality.

Results

Of 56,567 patients admitted to the hospital during the study period, 49,518 were included. Of these, 87.8% had no evidence of kidney dysfunction, 11.0% had AKI, and 1.1% had s-AKI. Patients with s-AKI had mild renal dysfunction in 82.7% of cases, moderate in 12.1%, and severe in 5.0%. Worsening s-AKI category was linearly correlated with hospital mortality, as previously described for AKI (no injury: 1.2%, mild: 6.5%, moderate: 12.9%, severe: 20.7%). Although mortality (8.0% versus 17.5%) and need for renal replacement therapy (0.2% versus 2.2%) were lower in patients with s-AKI than in those with AKI, multivariable regression analysis confirmed that s-AKI was an independent risk factor for hospital mortality (odds ratio (OR), 5.44; 95% confidence interval [95% CI], 3.89 to 7.44); the OR with AKI was 14.8 (95% CI, 13.2 to 16.7).

Conclusions

Close to 1% of hospitalized patients develop s-AKI. This condition is independently associated with increased hospital mortality, and the risk for death increases with s-AKI severity. Patients with s-AKI had a better outcome and were less likely to require renal replacement therapy than patients with AKI.     

AKI in Children Hospitalized with Nephrotic Syndrome

Background and objectives

Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome.

Design, setting, participants, & measurements

Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition.

Results

AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; P<0.001), and intensity of medication exposure (odds ratio, 1.34; 95% confidence interval, 1.09 to 1.65; P=0.01) remained significantly associated with AKI in children with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; P<0.001).

Conclusions

AKI is common in children hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission.     

Acute Respiratory Distress Syndrome and Risk of AKI among Critically Ill Patients

Background and objectives

Increasing experimental evidence suggests that acute respiratory distress syndrome (ARDS) may promote AKI. The primary objective of this study was to assess ARDS as a risk factor for AKI in critically ill patients.

Design, setting, participants, & measurements

This was an observational study on a prospective database fed by 18 intensive care units (ICUs). Patients with ICU stays >24 hours were enrolled over a 14-year period. ARDS was defined using the Berlin criteria and AKI was defined using the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria. Patients with AKI before ARDS onset were excluded.

Results

This study enrolled 8029 patients, including 1879 patients with ARDS. AKI occurred in 31.3% of patients and was more common in patients with ARDS (44.3% versus 27.4% in patients without ARDS; P<0.001). After adjustment for confounders, both mechanical ventilation without ARDS (odds ratio [OR], 4.34; 95% confidence interval [95% CI], 3.71 to 5.10) and ARDS (OR, 11.01; 95% CI, 6.83 to 17.73) were independently associated with AKI. Hospital mortality was 14.2% (n=1140) and was higher in patients with ARDS (27.9% versus 10.0% in patients without ARDS; P<0.001) and in patients with AKI (27.6% versus 8.1% in those without AKI; P<0.001). AKI was associated with higher mortality in patients with ARDS (42.3% versus 20.2%; P<0.001).

Conclusions

ARDS was independently associated with AKI. This study suggests that ARDS should be considered as a risk factor for AKI in critically ill patients.