[Human Resources Development in Emergency Department]. / Personalentwicklung in der Notaufnahme.

In the last years, the number of patients in German emergency department (ED) is rising continously. At the same time, it is diffcult to find enough physicians to occupy the positions in the ED. Therefore human resources development is critical for the success of any ED. This article describes human resources development and recruitment in the context of current health policy trends in Germany.

Urinary [TIMP-2]·[IGFBP7]-guided randomized controlled intervention trial to prevent acute kidney injury in the emergency department.

BACKGROUND: Early detection and prevention of acute kidney injury (AKI) is important to reduce morbidity and mortality. Discovery of early-detection biomarkers has enabled early preventive approaches. There are no data on early biomarker-guided intervention with nephrological consultation in emergency departments (EDs). METHODS: In this prospective randomized controlled intervention trial, patients at high risk for AKI were screened with urinary [TIMP-2]·[IGFBP7] in the ED of Robert-Bosch-Hospital (Stuttgart, Germany). We screened 257 eligible patients of whom 100 met the inclusion criteria, with urinary [TIMP-2]·[IGFBP7] >0.3, and were included. The intervention group received immediate one-time nephrological consultation after randomization, implementing Kidney Disease: Improving Global Outcomes (KDIGO) 2012 recommendations on AKI. The primary outcome was the incidence of moderate to severe AKI within the first day after admission. Secondary outcomes were AKI occurrence within 3 days after admission, need for renal replacement therapy (RRT), length of hospital stay and death. RESULTS: The primary outcome did not differ significantly (P = 0.9) between the groups, neither within the first day nor within the first 3 days after admission. The intervention group had significantly (P < 0.05) lower serum creatinine (SCr) on Day 2 and lower maximum SCr and tended (P = 0.08) to have higher urine output (UOP) at Day 3 than the non-intervention group. No patient in the intervention group needed RRT (0 versus 3) during the hospital stay (P = 0.09). CONCLUSIONS: One-time routine nephrologist-guided application of the KDIGO bundle in ED patients with a risk for AKI cannot currently be recommended. However, due to the uniform trend of study endpoints in favour of intervention, further trials to investigate larger cohorts of more severely ill patients are warranted. TRIAL REGISTRATION: www.ClinicalTrials.gov, study number NCT02730637.

Urinary [TIMP-2] × [IGFBP7] for risk prediction of acute kidney injury in decompensated heart failure.

BACKGROUND: In acute decompensated heart failure (ADHF) the risk of acute kidney injury (AKI) is high. Early detection of patients at risk for AKI is important. We tested urinary [TIMP-2] × [IGFBP7], a new US Food and Drug Administration-cleared test to assess AKI risk, in a cohort of hospitalized ADHF patients. HYPOTHESIS: In patients with ADHF, urinary [TIMP-2] × [IGFBP7] is associated with moderate to severe AKI and related to increased mortality. METHODS: We enrolled 400 patients in the emergency department at Robert-Bosch Hospital, Stuttgart, Germany. We examined the predictive ability of urinary [TIMP-2] × [IGFBP7] (units: [ng/mL]2 /1000) for development of AKI stage 2 or 3 within 24 hours of sample collection in patients with ADHF. Operating characteristics were determined for the validated cutoffs of 0.3 and 2.0. RESULTS: Forty patients had ADHF upon presentation and sufficient data for AKI staging. 27.5% developed AKI stage 2-3 within 7 days. Urinary [TIMP-2] × [IGFBP7] discriminated for AKI stage 2-3 over the first day with an area under the ROC curve of 0.84 (95% confidence interval: 0.72-0.93) and over 7 days with an AUC of 0.77 (95% confidence interval: 0.65-0.88). For the first day, sensitivity was 86% at the 0.3 cutoff and specificity was 95% at the 2.0 cutoff for prediction of AKI stage 2-3. There was a trend (P = 0.08) for higher mortality in patients with urinary [TIMP-2] × [IGFBP7] >2.0 and AKI 2-3. CONCLUSIONS: Urinary [TIMP-2] × [IGFBP7] is a promising marker for AKI risk assessment in patients with ADHF.

The Influence of Thyroid Function, Inflammation, and Obesity on Risk Prediction of Acute Kidney Injury by Cystatin C in the Emergency Department.

BACKGROUND/AIMS: There is a growing role for emergency departments (ED) in assessing acute kidney injury (AKI) for hospital admissions but there are few studies addressing acute kidney injury biomarkers and confounding factors in the ED. Cystatin C (CysC), a newer renal biomarker, is influenced by thyroid function, inflammation and obesity. This study aims to be the first study to address the impact of these parameters in the ED. METHODS: Admitted patients (n=397) were enrolled in the ED at Robert-Bosch-Hospital, Stuttgart, Germany. Daily serum creatinine (sCr) was recorded for AKI classification by Kidney Diseases Improves Global Outcome (KDIGO) criteria. CysC, thyroid stimulating hormone (TSH), thyroxine (T4), C-reactive protein (CRP) and body mass index (BMI) were registered at enrollment in the ED. Serum samples were collected at enrollment, after 6 hours and in the following mornings (day 1 to day 3). The correlation of CysC and sCr was studied on a two variable logistic regression model. A linear predictor was computed to predict minimal AKI stage and area under the curve (AUC) was calculated. RESULTS: Of 397 patients enrolled for classification by KDIGO AKI criteria, n=152 (38%) developed AKI, n=69 (17.4%) reached AKI stage I, n=70 (17.6%) AKI stage II, and n=13 (3%) AKI stage III. Although a correlation between CRP and CysC levels was shown (rho=0.376), this didn't affect the predictive ability for AKI according to our data. We compared receiver operating characteristic (ROC) curves (DeLong test) of CysC to ROC curves of CysC with the additional variables TSH, BMI, and CRP respectively. Our data shows that addition of CRP, TSH, or BMI does not improve prediction of AKI stage beyond prediction based solely on CysC levels. CONCLUSIONS: CysC is known to be influenced by thyroid function, inflammation and obesity, but in our large ED population there was no significant impact of these factors on the diagnostic accuracy of CysC to detect AKI in ED patients.

Urinary [TIMP-2]·[IGFBP7] - Novel Biomarkers to Predict Acute Kidney Injury.

BACKGROUND: Urine microscopy is an established technique to assess kidney disease, and can add valuable information about the mechanism of damage. However, it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in practice. A rapid biomarker test that identifies patients from the emergency department (ED) who are likely to have positive urine microscopy findings would enable more efficient use of this technique. METHODS: Four hundred patients were enrolled in the ED; thereof 362 patients had available both tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2]·[IGFBP7] and urine score (U-Score) data at enrollment. U-Score was assessed through urine microscopy as described previously. RESULTS: Fifteen (4%) of 362 patients had a U-Score >0. When patients were stratified into 3 groups using the validated [TIMP-2]·[IGFBP7] cutoffs of 0.3 and 2.0, the proportion of patients with a positive U-Score increased across the 3 strata from 1 to 6 to 24% (p < 0.001). At the 0.3 cutoff, [TIMP-2]·[IGFBP7] had a sensitivity of 87%, specificity of 62% and negative predictive value (NPV) of 99% for prediction of a positive U-Score. At the 2.0 cutoff, specificity increased to 95% and positive predictive value (PPV) increased to 24%. CONCLUSIONS: In ED patients, urinary [TIMP-2]·[IGFBP7] had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary [TIMP-2]·[IGFBP7] may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources. SUMMARY: Urine microscopy is an established technique to assess acute kidney injury and can add valuable information about the mechanism of damage; however it requires the time and expertise of an experienced nephrologist and, therefore, is typically used for a limited number of patients in clinical practice. We have shown in ED patients, urinary [TIMP-2]·[IGFBP7] had a high NPV (99%) for ruling out a positive U-Score using the 0.3 cutoff and had a PPV of 24% (6-fold greater than the pre-test probability) using the 2.0 cutoff. As such, urinary [TIMP-2]·[IGFBP7] may enable more effective use of urine microscopy in these patients and thereby save time and personnel resources.

Association of Renal Stress/Damage and Filtration Biomarkers with Subsequent AKI during Hospitalization among Patients Presenting to the Emergency Department.

BACKGROUND AND OBJECTIVES: Emergency departments (EDs) have a growing role in hospital admissions, but few studies address AKI biomarkers in the ED. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients admitted to the internal medicine service were enrolled during initial workup in the ED at Robert-Bosch-Hospital, Stuttgart, Germany. Daily serum creatinine (sCr) and urine output (UO) were recorded for AKI classification by Kidney Disease Improving Global Outcomes (KDIGO) criteria. Cystatin C, kidney injury molecule-1, liver-type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were measured in blood and urine, and IL-18, insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor of metalloproteinases-2 (TIMP-2) and [TIMP-2]⋅[IGFBP7] were measured in urine collected at enrollment, after 6 hours, and the following morning. Association between these biomarkers and the end point of moderate-severe AKI (KDIGO stage 2-3) occurring within 12 hours of each sample collection was examined using generalized estimating equation logistic regression. Performance for prediction of the AKI end point using two previously validated [TIMP-2]-[IGFBP7] cutoffs was also tested. RESULTS: Of 400 enrolled patients, 298 had sufficient sCr and UO data for classification by KDIGO AKI criteria: AKI stage 2 developed in 37 patients and AKI stage 3 in nine patients. All urinary biomarkers, sCr, and plasma cystatin C had statistically significant (P<0.05) odds ratios (ORs) for the AKI end point. In a multivariable model of the urine biomarkers and sCr, only [TIMP-2]⋅[IGFBP7] and sCr had statistically significant ORs. Compared with [TIMP-2]⋅[IGFBP7]<0.3 (ng/ml)(2)/1000, values between 0.3 and 2.0 (ng/ml)(2)/1000 indicated 2.5 (95% confidence interval [95% CI], 1.1 to 5.2) times the odds for the AKI end point and values >2.0 (ng/ml)(2)/1000 indicated 11.0 (95% CI, 4.4 to 26.9) times the odds. Addition of [TIMP-2]⋅[IGFBP7] to a clinical model significantly improved area under the receiver-operating characteristic curve from 0.67 (95% CI, 0.61 to 0.78) to 0.77 (95% CI, 0.72 to 0.86) (P<0.001); however, including both markers in the model was not significantly different from including either marker alone. CONCLUSIONS: Urinary [TIMP-2]⋅[IGFBP7] with pre-established cutoffs provides valuable information about risk for imminent AKI in the ED that is complementary to sCr and clinical risk factors.