Kidney Cell Cycle Arrest and Cardiac Biomarkers and Acute Kidney Injury Following Angiography: The Prevention of Serious Adverse Events Following Angiography (PRESERVE) Study.

Rationale & Objective: Recent studies in patients with chronic kidney disease (CKD) indicate that most cases of contrast-associated acute kidney injury (CA-AKI) are mild and are not associated with elevation in kidney injury biomarkers. We used highly sensitive kidney cell cycle arrest and cardiac biomarkers to assess the risk of CA-AKI and major adverse kidney events in patients with CKD undergoing angiography. Study Design: A retrospective study. Setting & Participants: A subset of 922 participants from the Prevention of Serious Adverse Events following Angiography trial. Predictors: Pre- and postangiography urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7 were measured in 742 subjects, and plasma ß natriuretic peptide (BNP) and high-sensitivity C-reactive protein (hs-CRP), and serum troponin (Tn) in 854 participants using samples obtained 1-2 hours before and 2-4 hours after angiography. Outcomes: CA-AKI and major adverse kidney events. Analytical Approach: We fitted logistic regression to examine association and area under the receiver operating characteristic curves for risk prediction. Results: There were no differences in postangiography urinary [TIMP-2]•[IGFBP7], plasma BNP, serum Tn, and hs-CRP concentrations among patients with and without CA-AKI and major adverse kidney events. However, higher pre- and postangiography median plasma BNP (pre: 200.0 vs 71.5, pg/mL, P = 0.05; post: 165.0 vs 81 pg/mL, P = 0.02); serum Tn (pre: 0.03 vs 0.01, ng/mL, P < 0.001; post, 0.04 vs 0.02, ng/mL, P = 0.01); and hs-CRP (pre: 9.55 vs 3.40 mg/L, P = 0.01; post: 9.90 vs 3.20 mg/L, P = 0.002) concentrations were associated with major adverse kidney events, although their discriminatory capacity was only modest (area under the receiver operating characteristic curves <0.7). Limitations: Most participants were men. Conclusions: Most mild CA-AKI cases are not associated with urinary cell cycle arrest biomarker elevation. Significant elevation in preangiography cardiac biomarkers may reflect patients with more significant cardiovascular disease that may predispose to poor long-term outcomes independent of CA-AKI status.

Association of Metformin Use During Hospitalization and Mortality in Critically Ill Adults With Type 2 Diabetes Mellitus and Sepsis.

OBJECTIVES: Whether metformin exposure is associated with improved outcomes in patients with type 2 diabetes mellitus and sepsis. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 16 hospitals in Pennsylvania from October 2008 to December 2014. PATIENTS: Adult critical ill patients with type 2 diabetes mellitus and sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective cohort study to compare 90-day mortality in diabetic patients with sepsis with and without exposure to metformin during hospitalization. Data were obtained from the electronic health record of a large healthcare system in Pennsylvania from October 2008 to December 2014, on patients admitted to the ICU at any of the 16 hospitals within the system. The primary outcome was mortality at 90 days. The absolute and adjusted odds ratio (OR) with 95% CI were calculated in a propensity score-matched cohort. Among 14,847 patients with type 2 diabetes mellitus and sepsis, 682 patients (4.6%) were exposed to metformin during hospitalization and 14,165 (95.4%) were not. Within a total of 2,691 patients subjected to propensity score-matching at a 1:4 ratio, exposure to metformin (n = 599) was associated with decreased 90-day mortality (71/599, 11.9% vs 475/2,092, 22.7%; OR, 0.46; 95% CI, 0.35-0.60), reduced severe acute kidney injury (50% vs 57%; OR, 0.75; 95% CI, 0.62-0.90), less Major Adverse Kidney Events at 1 year (OR, 0.27; 95% CI, 0.22-0.68), and increased renal recovery (95% vs 86%; OR, 6.43; 95% CI, 3.42-12.1). CONCLUSIONS: Metformin exposure during hospitalization is associated with a decrease in 90-day mortality in patients with type 2 diabetes mellitus and sepsis.

Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care Practitioners.

OBJECTIVES: To assess the attitudes of practitioners with respect to net ultrafiltration prescription and practice among critically ill patients with acute kidney injury treated with renal replacement therapy. DESIGN: Multinational internet-assisted survey. SETTING: Critical care practitioners involved with 14 societies in 80 countries. SUBJECTS: Intervention: MEASUREMENT AND MAIN RESULTS:: Of 2,567 practitioners who initiated the survey, 1,569 (61.1%) completed the survey. Most practitioners were intensivists (72.7%) with a median duration of 13.2 years of practice (interquartile range, 7.2-22.0 yr). Two third of practitioners (71.0%; regional range, 55.0-95.5%) reported using continuous renal replacement therapy with a net ultrafiltration rate prescription of median 80.0 mL/hr (interquartile range, 49.0-111.0 mL/hr) for hemodynamically unstable and a maximal rate of 299.0 mL/hr (interquartile range, 200.0-365.0 mL/hr) for hemodynamically stable patients, with regional variation. Only a third of practitioners (31.5%; range, 13.7-47.8%) assessed hourly net fluid balance during continuous renal replacement therapy. Hemodynamic instability was reported in 20% (range, 20-38%) of patients and practitioners decreased the rate of fluid removal (70.3%); started or increased the dose of a vasopressor (51.5%); completely stopped fluid removal (35.8%); and administered a fluid bolus (31.6%), with significant regional variation. Compared with physicians, nurses were most likely to report patient intolerance to net ultrafiltration (73.4% vs 81.3%; p = 0.002), frequent interruptions (40.4% vs 54.5%; p < 0.001), and unavailability of trained staff (11.9% vs 15.6%; p = 0.04), whereas physicians reported unavailability of dialysis machines (14.3% vs 6.1%; p < 0.001) and costs associated with treatment as barriers (12.1% vs 3.0%; p < 0.001) with significant regional variation. CONCLUSIONS: Our study provides new knowledge about the presence and extent of international practice variation in net ultrafiltration. We also identified barriers and specific targets for quality improvement initiatives. Our data reflect the need for evidence-based practice guidelines for net ultrafiltration.

Intensive Monitoring of Urine Output Is Associated With Increased Detection of Acute Kidney Injury and Improved Outcomes.

BACKGROUND: Urine output (UO) is a vital sign for critically ill patients, but standards for monitoring and reporting vary widely between ICUs. Careful monitoring of UO could lead to earlier recognition of acute kidney injury (AKI) and better fluid management. We sought to determine if the intensity of UO monitoring is associated with outcomes in patients with and those without AKI. METHODS: This was a retrospective cohort study including 15,724 adults admitted to ICUs from 2000 to 2008. Intensive UO monitoring was defined as hourly recordings and no gaps > 3 hours for the first 48 hours after ICU admission. RESULTS: Intensive monitoring for UO was conducted in 4,049 patients (26%), and we found significantly higher rates of AKI (OR, 1.22; P < .001) in these patients. After adjustment for age and severity of illness, intensive UO monitoring was associated with improved survival but only among patients experiencing AKI. With or without AKI, patients with intensive monitoring also had less cumulative fluid volume (2.98 L vs 3.78 L; P < .001) and less fluid overload (2.49% vs 5.68%; P < .001) over the first 72 hours of ICU stay. CONCLUSIONS: In this large ICU population, intensive monitoring of UO was associated with improved detection of AKI and reduced 30-day mortality in patients experiencing AKI, as well as less fluid overload for all patients. Our results should help inform clinical decisions and ICU policy about frequency of monitoring of UO, especially for patients at high risk of AKI or fluid overload, or both.

Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival.

OBJECTIVE: We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes. DESIGN: We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads. SETTING: University Medical Center. PATIENTS: Patients admitted to ICUs from 2000 to 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year. CONCLUSIONS: Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

Serum Neutrophil Gelatinase-Associated Lipocalin Predicts Survival After Resuscitation From Cardiac Arrest.

OBJECTIVES: In the first days after cardiac arrest, accurate prognostication is challenging. Serum biomarkers are a potentially attractive adjunct for prognostication and risk stratification. Our primary objective in this exploratory study was to identify novel early serum biomarkers that predict survival after cardiac arrest earlier than currently possible. DESIGN: Prospective, observational study. SETTING: A single academic medical center. SUBJECTS: Adult subjects who sustained cardiac arrest with return of spontaneous circulation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We obtained blood samples from each subject at enrollment, 6, 12, 24, 48, and 72 hours after return of spontaneous circulation. We measured the serum levels of novel biomarkers, including neutrophil gelatinase-associated lipocalin, high-mobility group protein B1, intracellular cell adhesion molecule-1, and leptin, as well as previously characterized biomarkers, including neuron-specific enolase and S100B protein. Our primary outcome of interest was survival-to-hospital discharge. We compared biomarker concentrations at each time point between survivors and nonsurvivors and used logistic regression to test the unadjusted associations of baseline clinical characteristics and enrollment biomarker levels with survival. Finally, we constructed a series of adjusted models to explore the independent association of each enrollment biomarker level with survival. A total of 86 subjects were enrolled. Enrollment levels of high-mobility group protein B1, neutrophil gelatinase-associated lipocalin, and S100B were higher in nonsurvivors than survivors. Enrollment leptin, neuron-specific enolase, and intracellular cell adhesion molecule-1 levels did not differ between nonsurvivors and survivors. The discriminatory power of enrollment neutrophil gelatinase-associated lipocalin level was the greatest (c-statistic, 0.78 [95% CI, 0.66-0.90]) and remained stable across all time points. In our adjusted models, enrollment neutrophil gelatinase-associated lipocalin level was independently associated with survival even after controlling for the development of acute kidney injury, and its addition to clinical models improved overall predictive accuracy. CONCLUSIONS: Serum neutrophil gelatinase-associated lipocalin levels are strongly predictive of survival-to-hospital discharge after cardiac arrest.

Risk factors for acute kidney injury in older adults with critical illness: a retrospective cohort study.

BACKGROUND: Risk for acute kidney injury (AKI) in older adults has not been evaluated systematically. We sought to delineate the determinants of risk for AKI in older compared with younger adults. STUDY DESIGN: Retrospective analysis of patients hospitalized in July 2000 to September 2008. SETTING & PARTICIPANTS: We identified all adult patients admitted to an intensive care unit (n=45,655) in a large tertiary-care university hospital system. We excluded patients receiving dialysis or a kidney transplant prior to hospital admission and patients with baseline creatinine levels ≥ 4mg/dL, liver transplantation, indeterminate AKI status, or unknown age, leaving 39,938 patients. PREDICTOR: We collected data for multiple susceptibilities and exposures, including age, sex, race, body mass, comorbid conditions, severity of illness, baseline kidney function, sepsis, and shock. OUTCOMES: We defined AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. We examined susceptibilities and exposures across age strata for impact on the development of AKI. MEASUREMENTS: We calculated area under the receiver operating characteristic curve (AUC) for prediction of AKI across age groups. RESULTS: 25,230 (63.2%) patients were 55 years or older. Overall, 25,120 (62.9%) patients developed AKI (69.2% aged ≥55 years). Examples of risk factors for AKI in the oldest age category (≥75 years) were drugs (vancomycin, aminoglycosides, and nonsteroidal anti-inflammatories), history of hypertension (OR, 1.13; 95% CI, 1.02-1.25), and sepsis (OR, 2.12; 95% CI, 1.68-2.67). Fewer variables remained predictive of AKI as age increased and the model for older patients was less predictive (P<0.001). For the age categories 18 to 54, 55 to 64, 65 to 74, and 75 years or older, AUCs were 0.744 (95% CI, 0.735-0.752), 0.714 (95% CI, 0.702-0.726), 0.706 (95% CI, 0.693-0.718), and 0.673 (95% CI, 0.661-0.685), respectively. LIMITATIONS: Analysis may not apply to non-intensive care unit patients. CONCLUSIONS: The likelihood of developing AKI increases with age; however, the same variables are less predictive for AKI as age increases. Efforts to quantify risk for AKI may be more difficult in older adults.