Derivation of Urine Output Thresholds That Identify a Very High Risk of AKI in Patients with Septic Shock : Clinical Journal of the American Society of Nephrology

Journal Logo

Advanced Search
Original Articles

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

Leedahl, David D.*; Frazee, Erin N.†; Schramm, Garrett E.†; Dierkhising, Ross A.‡; Bergstralh, Eric J.‡; Chawla, Lakhmir S.§; Kashani, Kianoush B.‖

Author Information

*Pharmacy Services, Sanford Medical Center, Fargo, North Dakota;

†Pharmacy Services,

‡Division of Biomedical Statistics and Informatics, and

‖Division of Nephrology and Hypertension and Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota; and

§Department of Anesthesiology and Critical Care Medicine and Division of Renal Diseases and Hypertension, George Washington University Medical Center, Washington, DC

Correspondence: Dr. Erin N. Frazee, Mayo Clinic, 200 First Street SW, Rochester, MN 55902. Email: [email protected]

Received September 9, 2013

Accepted March 19, 2014

Online date: May 01, 2014

Clinical Journal of the American Society of Nephrology 9(7):p 1168-1174, July 2014. | DOI: 10.2215/CJN.09360913
  • Free
  • SDC

Abstract

Introduction

Despite advances in the detection and treatment of AKI in critically ill patients, mortality from this condition remains alarmingly high (1–4). Among the array of renal failure causes, septic shock elicits particular concern: the incidence of AKI in this setting may exceed 60% (5,6). The combination of septic shock and AKI yields a nearly 2-fold risk of death compared with either alone (2,5). Therefore, tools for early detection of AKI in the septic patient are necessary to minimize delays in diagnosis and treatment.

Although definitions of AKI have varied historically, the Kidney Disease Improving Global Outcomes (KDIGO) working group has recently developed standard diagnostic criteria based on serum creatinine (SCr) and consecutive duration of oliguria (7,8). However, these criteria are difficult to interpret in a critically ill patient with varying SCr production and volume of distribution (9,10). Although the KDIGO urine output criterion requires >6 hours of oliguria for “risk of AKI” (stage I) and ≥12 hours of oliguria for stage II AKI, shorter durations are gaining clinical significance and may serve as an early clinical alarm for AKI (11–13).

The discovery of novel renal biomarkers and integration of real-time electronic alerts into clinical practice have reinvigorated interest in early detection of AKI (14,15). Unfortunately, routine use of these biomarker assays and electronic notification systems require significant clinical and financial resources. To enhance early, accessible, and cost-effective bedside identification of AKI risk in critical illness, experts have proposed the concept of renal angina (16–19). Renal angina is a conceptual clinical definition to operationalize and structure the pretest probability assessment for diagnosing AKI prospectively. The use of renal angina parallels the changing paradigm for many critical illnesses, wherein diagnoses pair radiographic imaging and laboratory evaluation with a patient’s pretest probability for a given disease state (20–22). The original renal angina concept categorized patients in one of three hazard levels based on a patient’s predisposition for AKI development (Supplemental Figure 1). Goldstein and Chawla proposed that adult patients with septic shock make up the highest risk hazard level for AKI. In other words, because of the high baseline risk associated with septic shock, minimal clinical evidence of kidney injury (sub-KDIGO evidence, known as adult renal angina [aRA]) should be used to identify patients at particular risk for the development of AKI (16). The proposed aRA model may facilitate earlier identification of AKI; however, this tool has yet to be derived or validated. Thus, we sought to derive the aRA model and characterize its ability to predict subsequent achievement of stage II or III (stage II+) AKI criteria among patients with septic shock.

Materials and Methods

Participant Identification

This retrospective analysis of a prospectively collected database examined adults with septic shock admitted to a 24-bed medical intensive care unit (ICU) at Mayo Clinic in Rochester, Minnesota, from January 2008 through December 2010 (23). The study ICU was staffed by a multidisciplinary team lead by intensivists 24/7 in house (24). The investigation was approved by the institutional review board with a waiver of informed consent and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. We included patients older than 18 years of age with a systolic BP<90 mm Hg despite a fluid challenge of 20 ml/kg body weight of crystalloid or equivalent colloid, based on recommendations from the 2008 Surviving Sepsis Campaign (25). Treatment of septic shock was uniformly guided by our sepsis resuscitation bundle, which has been described previously (23). Exclusion criteria were applied in two stages to derive the study cohort (Figure 1). The first stage involved collection of data readily available by electronic query, and the second stage involved collection of data requiring manual abstraction or evaluation from the patient’s medical record. Patients having severe sepsis without shock, those with a history of ESRD, and those lacking research authorization were excluded from study eligibility. A random-number generator was used to select a subset of eligible patients who were then screened according to our study protocol (Figure 1).

F1-6
Figure 1:
A 390-patient cohort was included in the final analysis. ICD-9, International Classification of Diseases, Ninth Revision; KDIGO, Kidney Disease Improving Global Outcomes.

Study Protocol

Figure 2 illustrates our a priori–defined study protocol. To briefly summarize, patients were followed from septic shock recognition (hour 0) to hour 96. Hour 0 urine output was disregarded because of presumed retention of urine volume in the bladder at the time of catheterization. Urine output was recorded until ICU discharge, urinary catheter removal, or hour 96, whichever came first. The “aRA window” encompassed hours 1–12 wherein patients were assessed for the first episode of consecutive oliguria and baseline to peak SCr level increase. This cutoff point at hour 12 ensured that, by definition, patients would be unable to meet KDIGO stage II urine output criterion (>12 hours of oliguria) during the aRA window. To avoid including patients with early septic AKI, we excluded any individual who met KDIGO stage II SCr criterion (doubled SCr from baseline) from an initial SCr level within 12 hours from septic shock recognition. The primary outcome of stage II+ AKI and secondary outcome of RRT were analyzed at hour 96. All-cause mortality was assessed at 28 days.

F2-6
Figure 2:
Adult renal angina and AKI were assessed in a stepwise protocol. *KDIGO criteria by baseline to peak SCr level increase or consecutive oliguria. KDIGO, Kidney Disease Improving Global Outcomes; SCr, serum creatinine; UOP, urine output.

Data Collection and Definitions

Abstracted data pertained to demographic characteristics (age, sex, race, admission weight, comorbid conditions), severity of illness (Acute Physiology and Chronic Health Evaluation [APACHE] III score, vasopressor administration), and renal measures (urine output, SCr, RRT). Baseline SCr was calculated as the average of available SCr values within 6 months of hospitalization. When previous SCr values were not available, the lowest hospital SCr was used to estimate baseline renal function (26,27). Urine output was documented hourly in the electronic medical record after urinary catheter placement. Urine output charted as “0” was considered a true value. In the rare event that urine output charting was missing between hourly values, the subsequent recorded urine output value was divided evenly with the previous missing hours. To determine baseline to peak SCr level, the baseline SCr level was subtracted from the highest SCr level available in the first 12 hours after septic shock recognition. No formal criteria existed for RRT initiation during the study period. Use of RRT was per intensivist and attending nephrologist discretion and was individualized for each patient.

The time of septic shock recognition was defined according to the 2008 Surviving Sepsis Campaign consensus criteria at the time of documented hypotension despite 20 ml/kg crystalloid or equivalent colloid (28). No patients in the study received hydroxyethyl starch. If a colloid was used, it was 5% or 25% albumin. For patients transferred from outside hospitals with septic shock, the admission time was considered the time of septic shock recognition. To account for severity of illness, APACHE III scores were calculated upon ICU admission. Only the first episode of consecutive oliguria was evaluated, with oliguria defined as urine output<0.5 ml/kg per hour based on actual admission body weight (8,13). The primary outcome of stage II+ AKI was defined as achieving stage II or III KDIGO criteria (8).

Physician order priority (stat or routine) dictated the specimen type collected (plasma or serum) for creatinine measurement. Creatinine was measured using the standardized (isotope dilution mass spectrometry traceable) Roche enzymatic creatinine assay. For patients receiving intravenous catecholamine therapy, our institution used an isotope dilution mass spectrophotometry–traceable Roche rate–Jaffe creatinine assay (Roche Cobas Integra 400 Plus chemistry analyzer) to avoid interference with enzymatic assays.

Statistical Analyses

Categorical variables were summarized as frequencies (percentages). Continuous variables were expressed as medians with interquartile ranges. Assuming an approximate 30% overall incidence of stage II+ AKI and 25% exclusion rate with equal sample sizes, it was determined that an initial sample of 530 patients (400 included patients) would provide 99% power to detect a difference of 20% in the incidence of AKI between patients with and without aRA (depending on definition derived) (29). Univariate logistic regression was performed to analyze the association of the initial duration of consecutive oliguria, baseline to peak SCr level, and APACHE III score with the end points of stage II+ AKI, RRT, and 28-day mortality. A multivariable logistic regression model including all three variables was used to estimate the predictive contribution of all variables simultaneously. Two-way interactions were assessed and were not found to be statistically significant, so were not considered further. Receiver-operating characteristic (ROC) curves and the areas under the curves (AUCs) were used to assess discriminative power and are reported with 95% confidence intervals (95% CI). We defined an AUC of 0.5–0.6 as demonstrating no predictive ability, 0.6–0.7 as demonstrating poor predictive ability, 0.7–0.8 as demonstrating fair predictive ability, 0.8–0.9 as demonstrating good predictive ability, and >0.9 as demonstrating outstanding predictive ability (13). Binary prediction rules were applied to calculate sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Data were analyzed with SAS software, version 9.2 (SAS Institute Inc., Cary, NC).

Results

Three hundred ninety patients were included in the final analysis (Figure 1). Prehospitalization SCr was available for 86.7% of patients and was estimated in 13.3% (Table 1). At hour 96, 98 (25.1%) patients had achieved criteria for stage II+ AKI (58 patients stage II and 40 patients, stage III) and 33 (8.5%) had received RRT. Two patients received RRT after hour 96 (hours 167 and 174, respectively) and were not considered for the outcome of RRT by hour 96. Ninety-seven patients (24.9%) died by day 28.

T1-6
Table 1:
Baseline characteristics

Univariate logistic regression analysis revealed a statistically significant positive association between hours of consecutive oliguria and development of stage II+ AKI, need for RRT, and 28-day mortality. In contrast, baseline to peak SCr level increase was not associated with any outcome (Table 2). The multivariable model had good predictive ability for subsequently achieving stage II+ AKI criteria (AUC, 0.81; 95% CI, 0.76 to 0.87) and is included in Supplemental Figure 2. A sensitivity analysis that excluded patients in whom the baseline SCr was estimated by lowest hospital creatinine (n=52) yielded similar results (AUC, 0.80; 95% CI, 0.74 to 0.86) (Supplemental Figure 3). Excluding patients in septic shock transferred to the ICU from the emergency department or general ward (n=191) also demonstrated similar results (data not shown). No significant interaction was found between the requirement of vasopressors and consecutive oliguria for the outcome of stage II+ AKI by multiple logistic regression analysis (P=0.97). In the multivariable models for stage II+ AKI and need for RRT, consecutive oliguria was the sole variable with discriminatory power (Table 2).

T2-6
Table 2:
Univariate and multivariable logistic regression analyses (n=390)

Because the models suggested that consecutive oliguric hours was the only variable associated with stage II+ AKI, it was selected to define aRA (AUC, 0.82; 95% CI, 0.77 to 0.87). The ROC curve for a sensitivity analysis excluding patients without documented baseline SCr is displayed in Supplemental Figure 4. The discriminatory power of this tool, assessed by cutoff values for consecutive oliguria, is shown in Table 3. The cutoff of 5 hours maximized the sum of sensitivity and specificity, a suitable criterion to establish a good cutoff. Five hours of consecutive oliguria had good accuracy (82%; 95% CI, 79% to 86%) for prediction of subsequently achieving stage II+ AKI criteria with fair overall performance (AUC, 0.75; 95% CI, 0.69 to 0.80) (Table 4). However, 3 hours of oliguria achieved a similar overall performance (AUC, 0.73; 95% CI, 0.68 to 0.78) with an accuracy of 74% (95% CI, 70% to 78%). Patients who met criteria for the 3-hour oliguria cutoff received more fluid resuscitation than those who did not (1761 ml; 95% CI, 903 to 2618 ml; P<0.01). A scatterplot describing the association between fluid balance and oliguria duration, as well as our analysis of fluid balance for the 3- and 5-hour cutoff, may be found in Supplemental Figure 5 and Supplemental Table 1, respectively.

T3-6
Table 3:
Cutoff values for number of consecutive oliguric hours to predict achievement of stage II+ AKI criteria
T4-6
Table 4:
Comparison of 1-, 3-, and 5-hour cutoffs of consecutive oliguria for proposed adult renal angina definition to predict stage II+ AKI

Secondary ROC analyses, wherein the 3- and 5-hour cutoffs were analyzed for predictive ability to subsequently achieve any KDIGO AKI criteria (e.g., including stage I) are included in Supplemental Figures 6 and 7. To account for differences in relevant clinical variables between patients with and without aRA and between included and excluded patients, additional secondary analyses were performed and are summarized in Supplemental Figure 8 and Supplemental Tables 2–4.

Discussion

To our knowledge, the present study is the first known attempt to derive the oliguria component of aRA in septic shock. Before the findings of our investigation, alterations in urine output had been proposed as a sensitive marker for AKI in ICU patients (30). In addition, the novel concept of aRA had been proposed as a sub-KDIGO duration of consecutive oliguria and increase in SCr level over baseline in combination with a measure of illness severity (16). The original renal angina concept placed patients with septic shock in the “very high risk” hazard level, requiring only 1 hour of oliguria or a 0.1-mg/dl baseline to peak SCr level increase to achieve the proposed aRA definition (Supplemental Figure 1). We found that 3–5 hours of consecutive oliguria demonstrated the greatest predictive power for subsequent achievement of stage II+ AKI and was the most clinically useful definition of aRA in patients with septic shock. The results also suggested that baseline to peak SCr increase and APACHE III score negligibly influenced the model. As expected, APACHE III score remained significantly associated with 28-day mortality (Table 2). Therefore, our findings endorse the notion that pretest probability as assessed by aRA is not a severity-of-illness metric but rather an oliguria-based clinical alarm with potential to identify evolving AKI earlier in a patient’s clinical course.

A well designed, prospective multicenter trial by Prowle and colleagues has assessed the ability of consecutive oliguria to predict SCr-based AKI in critically ill patients (13). Our finding that 3–5 hours of consecutive oliguria is a reasonable definition for aRA is in agreement with Prowle and colleagues, who concluded that 4 hours of oliguria provided the best cumulative sensitivity and specificity for SCr-based AKI (52% and 86%, respectively). Our study expands on the work of Prowle and colleagues in several ways. Whereas their study looked at an oliguria-only variable for an SCr-based AKI outcome, we analyzed the association between both consecutive oliguria and SCr variables with the incidence of oliguria or SCr-based AKI. Prowle and colleagues evaluated a rather diverse 239-patient ICU population, whereas our study specifically evaluated a 390-patient cohort with septic shock treated uniformly with a bundled approach. The longest duration of consecutive oliguria on each day, used for analysis in Prowle and colleagues’ study, may be suboptimal for a clinical alarm. Because we desired to evaluate a tool to promote early identification of patients at high risk for AKI, we evaluated only the first episode of consecutive oliguria in the first 12 hours, simulating bedside assessment in real time.

Our findings agree with those of a recent study by Ralib and colleagues, who demonstrated that the current KDIGO definition of AKI may be too liberal in a general ICU population. In their analysis, a 6-hour urine output threshold of 0.3 ml/kg per hour yielded the optimal sensitivity and specificity for death or need for dialysis (61% and 77%, respectively). Our 3-hour urine output threshold of <0.5 ml/kg per hour in a septic shock population had similar predictive power for stage II+ AKI, need for dialysis, and 28-day mortality (31).

To our knowledge, this is the first published study that attempts to translate the aRA paradigm from theory to practice in adult patients with sepsis. The internal validity is strengthened by the homogeneity of our patient population and resuscitative efforts. All included patients were required to have documented systolic hypotension after a 20-ml/kg bolus (25). The 12-hour “aRA window” (Figure 2) and analysis of the first episode of consecutive oliguria was chosen to mimic assessment in the early phase of septic shock up to the KDIGO II urine output criterion (oliguria for >12 hours). Since timing of interventions is vital in septic shock and AKI, a 12-hour aRA cutoff simulates a time point where an intensivist may choose to provide additional interventions or observe. Finally, given the debate about the optimal end point for AKI, we chose the outcome of KDIGO stage II+ to analyze a severity of AKI that we deemed clearly clinically relevant.

Our study has several limitations. Urine output data were collected retrospectively and relied on accurate nurse charting, introducing the potential for inherent biases and unmeasured confounding variables. Although reflective of most clinical practices, SCr data were ordered at the discretion of the attending physician and relied on the measurements available for each patient. We cannot exclude the possibility that multiple measures of SCr or measuring SCr at the same time for each patient over the initial 12-hour window may have increased the predictive power of this variable for AKI. Fluid administration may have distorted SCr level measurements, but given the degree of fluid positivity in our patients, we anticipate at most a 0.1- to 0.2-mg/dl alteration in SCr would be present, which would not have meaningfully altered the findings (10). Diuretic use was not assessed because of the rare administration of such therapy to patients in the acute phase of shock. All patients receiving RRT had a primary renal indication (e.g., oliguria or anuria, hyperkalemia, fluid overload unresponsive to diuresis), but we cannot exclude the possibility that undetected or undocumented differences in the criteria to start RRT in our study may have influenced the results. We must also emphasize that we evaluated a patient cohort from the “very high risk” hazard level for aRA, and our definition does not apply to patient populations from lower hazard levels. This retrospective analysis of a prospectively collected septic shock cohort was conducted at a single ICU with predominantly white patients, and our definition of aRA from this study may not be generalizable to patients with different clinical scenarios, practice environments, or baseline risk factors for AKI. We feel it is important to address the position of aRA among other tools for AKI prediction, such as the renal angina index, which has been recently validated in a pediatric cohort (19). It is important to recognize that the concept of renal angina is subdivided into aRA and pediatric renal angina (pRA). The rationale for this distinction is based on the fact that the pediatric criteria use fluid overload and do not define AKI or pediatric renal angina using urine output. Although our findings demonstrated a statistical relationship between increased fluid overload and duration of oliguria, we cannot exclude the possibility that additional AKI risk factors (e.g., fluid balance) may have significantly contributed to AKI, RRT, or mortality in the aRA model (Supplemental Figure 5). However, the aRA criteria used in this study were congruent with the original aRA concept and KDIGO classification schema.

Our model of aRA provides an array of potential strengths. While most components of risk stratification are static (e.g., comorbid conditions, demographic characteristics, resuscitation measures), our proposed aRA definition of 3–5 hours of consecutive oliguria during the initial 12 hours after septic shock recognition provides a dynamic and responsive tool for the intensivist. Urine output is readily assessed at the bedside and already routinely collected, posing no additional laboratory costs. Our study promotes a culture of recording and reporting changes in hourly urine output for critically ill patients. If hourly urine output is documented, electronic alert mechanisms could be developed to actively survey for oliguria and facilitate patient assessment, fluid or vasopressor administration, nephrology specialist consultation, or early RRT before additional biochemical evidence of AKI is observed (32,33). Evaluating pretest probability using a 3-hour oliguria cutoff may aid in the decision to deploy other diagnostic tests (e.g., AKI biomarkers), potentially increasing their accuracy and cost-effectiveness (34). Finally, our definition of aRA may add value to an existing or investigational risk score for AKI in the ICU (35,36).

In conclusion, 3–5 hours of consecutive oliguria within 12 hours after septic shock recognition may provide a valuable measure of AKI risk. In practice, this would mean that once a patient with septic shock develops 3 hours of consecutive oliguria, the patient has adult renal angina. Further validation to support the proposed definition is needed.

Disclosures

None.

Acknowledgments

The authors thank Dr. Stuart Goldstein for his critical review of the manuscript for intellectual content. They also acknowledge the late Dr. Bekele Afessa for his expert guidance in database development and help with data collection.

Discretionary funds for statistical efforts were provided by Mayo Clinic Pharmacy Services.

Published online ahead of print. Publication date available at www.cjasn.org.

This article contains supplemental material online at http://cjasn.asnjournals.org/lookup/suppl/doi:10.2215/CJN.09360913/-/DCSupplemental.

References

1. Hoste EA, Schurgers M: Epidemiology of acute kidney injury: How big is the problem? Crit Care Med 36[Suppl]: S146–S151, 2008
2. Oppert M, Engel C, Brunkhorst FM, Bogatsch H, Reinhart K, Frei U, Eckardt KU, Loeffler M, John SGerman Competence Network Sepsis (Sepnet): Acute renal failure in patients with severe sepsis and septic shock—a significant independent risk factor for mortality: Results from the German Prevalence Study. Nephrol Dial Transplant 23: 904–909, 2008
3. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco CBeginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA 294: 813–818, 2005
    4. Bouchard J, Soroko SB, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RLProgram to Improve Care in Acute Renal Disease (PICARD) Study Group: Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney Int 76: 422–427, 2009
    5. Bagshaw SM, Lapinsky S, Dial S, Arabi Y, Dodek P, Wood G, Ellis P, Guzman J, Marshall J, Parrillo JE, Skrobik Y, Kumar ACooperative Antimicrobial Therapy of Septic Shock (CATSS) Database Research Group: Acute kidney injury in septic shock: Clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy. Intensive Care Med 35: 871–881, 2009
    6. Kim WY, Huh JW, Lim CM, Koh Y, Hong SB: A comparison of acute kidney injury classifications in patients with severe sepsis and septic shock. Am J Med Sci 344: 350–356, 2012
    7. Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, Tolwani AJ, Waikar SS, Weisbord SD: KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury. Am J Kidney Dis 61: 649–672, 2013
    8. Kidney DiseaseImproving Global Outcomes (KDIGO) Acute Kidney Injury Work Group: KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2: 1–138, 2012
    9. Kassirer JP: Clinical evaluation of kidney function—glomerular function. N Engl J Med 285: 385–389, 1971
    10. Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA, Paganini EP, Mehta RLProgram to Improve Care in Acute Renal Disease Study: Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients. Crit Care 14: R82, 2010
    11. Robert S, Zarowitz BJ: Is there a reliable index of glomerular filtration rate in critically ill patients? DICP 25: 169–178, 1991
    12. Doi K, Yuen PS, Eisner C, Hu X, Leelahavanichkul A, Schnermann J, Star RA: Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol 20: 1217–1221, 2009
      13. Prowle JR, Liu YL, Licari E, Bagshaw SM, Egi M, Haase M, Haase-Fielitz A, Kellum JA, Cruz D, Ronco C, Tsutsui K, Uchino S, Bellomo R: Oliguria as predictive biomarker of acute kidney injury in critically ill patients. Crit Care 15: R172, 2011
      14. Colpaert K, Hoste EA, Steurbaut K, Benoit D, Van Hoecke S, De Turck F, Decruyenaere J: Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class. Crit Care Med 40: 1164–1170, 2012
      15. Schilcher G, Ribitsch W, Otto R, Portugaller RH, Quehenberger F, Truschnig-Wilders M, Zweiker R, Stiegler P, Brodmann M, Weinhandl K, Horina JH: Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study). BMC Nephrol 12: 39, 2011
      16. Goldstein SL, Chawla LS: Renal angina. Clin J Am Soc Nephrol 5: 943–949, 2010
      17. Goldstein SL: Acute kidney injury biomarkers: Renal angina and the need for a renal troponin I. BMC Med 9: 135, 2011
        18. Basu RK, Chawla LS, Wheeler DS, Goldstein SL: Renal angina: An emerging paradigm to identify children at risk for acute kidney injury. Pediatr Nephrol 27: 1067–1078, 2012
          19. Basu RK, Zappitelli M, Brunner L, Wang Y, Wong HR, Chawla LS, Wheeler DS, Goldstein SL: Derivation and validation of the renal angina index to improve the prediction of acute kidney injury in critically ill children. Kidney Int 85: 659–667, 2014
          20. Cook DJ, Donadini MP: Pulmonary embolism in medical-surgical critically ill patients. Hematol Oncol Clin North Am 24: 677–682, vii, 2010
          21. Lauzier F, Ruest A, Cook D, Dodek P, Albert M, Shorr AF, Day A, Jiang X, Heyland DCanadian Critical Care Trials Group: The value of pretest probability and modified clinical pulmonary infection score to diagnose ventilator-associated pneumonia. J Crit Care 23: 50–57, 2008
            22. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky ASARDS Definition Task Force: Acute respiratory distress syndrome: The Berlin Definition. JAMA 307: 2526–2533, 2012
            23. Schramm GE, Kashyap R, Mullon JJ, Gajic O, Afessa B: Septic shock: A multidisciplinary response team and weekly feedback to clinicians improve the process of care and mortality. Crit Care Med 39: 252–258, 2011
            24. Gajic O, Afessa B, Hanson AC, Krpata T, Yilmaz M, Mohamed SF, Rabatin JT, Evenson LK, Aksamit TR, Peters SG, Hubmayr RD, Wylam ME: Effect of 24-hour mandatory versus on-demand critical care specialist presence on quality of care and family and provider satisfaction in the intensive care unit of a teaching hospital. Crit Care Med 36: 36–44, 2008
            25. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JLInternational Surviving Sepsis Campaign Guidelines CommitteeAmerican Association of Critical-Care NursesAmerican College of Chest PhysiciansAmerican College of Emergency PhysiciansCanadian Critical Care SocietyEuropean Society of Clinical Microbiology and Infectious DiseasesEuropean Society of Intensive Care MedicineEuropean Respiratory SocietyInternational Sepsis ForumJapanese Association for Acute MedicineJapanese Society of Intensive Care MedicineSociety of Critical Care MedicineSociety of Hospital MedicineSurgical Infection SocietyWorld Federation of Societies of Intensive and Critical Care Medicine: Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 36: 296–327, 2008
            26. Siew ED, Matheny ME, Ikizler TA, Lewis JB, Miller RA, Waitman LR, Go AS, Parikh CR, Peterson JF: Commonly used surrogates for baseline renal function affect the classification and prognosis of acute kidney injury. Kidney Int 77: 536–542, 2010
            27. Lafrance JP, Miller DR: Defining acute kidney injury in database studies: The effects of varying the baseline kidney function assessment period and considering CKD status. Am J Kidney Dis 56: 651–660, 2010
            28. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJThe ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest 101: 1644–1655, 1992
            29. Suh SH, Kim CS, Choi JS, Bae EH, Ma SK, Kim SW: Acute kidney injury in patients with sepsis and septic shock: Risk factors and clinical outcomes. Yonsei Med J 54: 965–972, 2013
            30. Macedo E, Malhotra R, Claure-Del Granado R, Fedullo P, Mehta RL: Defining urine output criterion for acute kidney injury in critically ill patients. Nephrol Dial Transplant 26: 509–515, 2011
            31. Md Ralib A, Pickering JW, Shaw GM, Endre ZH: The urine output definition of acute kidney injury is too liberal. Crit Care 17: R112, 2013
            32. Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, Bagshaw SM: A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: A systematic review and meta-analysis. Crit Care 15: R72, 2011
            33. Ponce D, Zorzenon Cde P, dos Santos NY, Balbi AL: Early nephrology consultation can have an impact on outcome of acute kidney injury patients. Nephrol Dial Transplant 26: 3202–3206, 2011
            34. de Geus HR, Betjes MG, Bakker J: Biomarkers for the prediction of acute kidney injury: a narrative review on current status and future challenges. Clin Kidney J 5: 102–108, 2012
            35. Cartin-Ceba R, Kashiouris M, Plataki M, Kor DJ, Gajic O, Casey ET: Risk factors for development of acute kidney injury in critically ill patients: A systematic review and meta-analysis of observational studies. Crit Care Res Pract 2012: 691013, 2012
            36. Demirjian S, Schold JD, Navia J, Mastracci TM, Paganini EP, Yared JP, Bashour CA: Predictive models for acute kidney injury following cardiac surgery. Am J Kidney Dis 59: 382–389, 2012
            Keywords:

            Acute kidney injury; intensive care units; septic shock; kidney function tests; early diagnosis; clinical alarms

            Copyright © 2014 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.