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

Kimmel, Martin; Shi, Jing; Latus, Joerg; Wasser, Christoph; Kitterer, Daniel; Braun, Niko; Alscher, Mark Dominik

doi:10.2215/cjn.10551015

Cited by 36 publications

(28 citation statements)

References 34 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[IGFBP7] for risk assessment of AKI in patients presenting to the ED [18]. In this subanalysis of our ED cohort, we examined the impact of thyroid function, inflammation and obesity on the performance of CysC in a nonintensive care unit (ICU) cohort of patients who presented to the ED.…”

Section: Introductionmentioning

confidence: 99%

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

Schanz¹,

Pannes²,

Dippon³

et al. 2016

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Schanz¹,

Pannes²,

Dippon³

et al. 2016

Kidney Blood Press Res

Self Cite

View full text Add to dashboard Cite

show abstract

“…We screened 400 patients presenting to the ED of the Robert Bosch Hospital (Stuttgart, Germany) as described elsewhere [12] . Admitted patients at least 18 years of age, with hemoglobin ≥ 9.5 g/ dl (women) or 10.5 g/dl (men), who were capable and willing to sign an informed consent were included.…”

Section: Methodsmentioning

confidence: 99%

“…Most promising are 2 markers of G1 cell cycle arrest, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulinlike growth factor-binding protein 7 (IGFBP7). Multiple studies have shown that the product of the concentration of these proteins [TIMP-2]·[IGFBP7] in urine is an early indicator of risk for AKI [8][9][10][11][12] . Additionally, urinary [TIMP-2]·[IGFBP7] was recently cleared by the US Food and Drug Administration (FDA) as the first available AKI-biomarker test in the US [13] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2016

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Many studies have shown that the product of the concentration of these proteins TIMP2·IGFBP7 in urine (Astute Medical, San Diego, CA, USA) is an early indicator of risk for AKI. [23][24][25][26][27][28] As the first available AKI biomarker test in the USA, urinary TIMP2·IGFBP7 was cleared in 2014 by the US FDA. 29 In this study, we tested the hypothesis that urinary TIMP2·IGFBP7 collected directly prior and after PBC administration can predict the development of AKI.…”

Section: Introductionmentioning

confidence: 99%

Urinary TIMP2·IGFBP7 for the prediction of platinum-induced acute renal injury

Schanz

Hoferer²,

Shi

et al. 2017

IJNRD

Self Cite

View full text Add to dashboard Cite

Introduction: Platinum-based chemotherapy (PBC) is a potent antineoplastic treatment, but cisplatin nephrotoxicity is often the limiting factor. Identifying the patients who are at risk for developing platinum-induced renal injury is an important issue. We tested urinary TIMP2·IGFBP7, a new US Food and Drug Administration (FDA)-cleared test to assess the risk of acute kidney injury (AKI), in a cohort of patients with malignant neoplastic disease receiving PBC. Patients and methods: A total of 58 patients with malignant neoplastic disease were enrolled in this study, of whom 32 patients had both urine samples and subsequent serum creatinine values available for detecting AKI within 72 hours. Urine samples were collected within 6 hours prior to PBC application and within 12 hours after the end of chemotherapy administration. We examined the predictive ability of TIMP2·IGFBP7 for the development of AKI as defined by KDIGO (Kidney Disease: Improving Global Outcomes) criteria within 72 hours after the administration of chemotherapy. Operating characteristics were determined for the previously validated TIMP2·IGFBP7 cutoff of 0.3 (ng/mL) 2 /1000. Results: Four (12.5%) patients developed AKI within 72 hours. Primary disease was lymphoma in 13 patients (40.6%) and solid tumors in 19 patients (59.4%). Eight patients (25.0%) received carboplatin and 24 (75.0%) cisplatin. TIMP2·IGFBP7 after PBC administration discriminated for the risk of AKI with an area under the receiver operating characteristic curve (AUC; 95% confidence interval) of 0.92 (0.80-1.00). At the cutoff of 0.3 for TIMP2·IGFBP7, sensitivity was 50%, specificity was 87%, negative predictive value was 95% and positive predictive value was 25% for the prediction of AKI within 72 hours. Conclusion: Urinary TIMP2·IGFBP7 measured in specimens gathered after PBC may be a useful tool to early identify patients who are at risk for developing platinum-induced AKI.

show abstract

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

Cited by 36 publications

References 34 publications

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

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

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

Urinary TIMP2·IGFBP7 for the prediction of platinum-induced acute renal injury

Contact Info

Product

Resources

About

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

Cited by 36 publications

References 34 publications

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

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

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

Urinary TIMP2&middot;IGFBP7 for the prediction of platinum-induced acute renal injury

Contact Info

Product

Resources

About

Urinary TIMP2·IGFBP7 for the prediction of platinum-induced acute renal injury