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Predictive potential of urinary biomarkers for early diagnosis of acute kidney injury in major elective abdominal non-vascular surgeries

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Author(s):
Lia Junqueira Marçal
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
Defense date:
Examining board members:
Leila Antonangelo; Adagmar Andriolo; Victor Faria Seabra
Advisor: Leila Antonangelo
Abstract

BACKGROUND: Acute kidney injury (AKI) incidence has increased significantly in the last years, and AKI has emerged as a worldwide health public problem. AKI has been associated with higher morbidity and early and late mortality, higher hospital length of stay and development of chronic kidney disease. AKI early diagnosis is extremely important to institute protective measures in order to prevent and/or minimize AKI development. Major surgeries patients have a high incidence of AKI associated with long-term adverse events. There is great interest on the study of postoperative AKI in this population, due to the possibility of estimating perioperative damage and establishing potential interventions. In this context, the use of biomarkers (BMs) to identify AKI high risk patients is extremely relevant. Most of the studies with BMs in surgical patients had assessed thoracic surgeries; there are few data on the role of urinary BMs of kidney structural injury in predicting AKI from patients submitted to major elective non-vascular abdominal surgeries. The present study aimed to assess the accuracy of urinary BMs for AKI prediction after major elective non-vascular abdominal surgeries. METHODS: A total of 298 patients submitted to major elective abdominal non-vascular surgeries were prospectively assessed. They were evaluated pre, peri-operatively and from the ICU admission up to seven days. Serum creatinine (sCr) was evaluated before surgery and once a day up to seven days or until ICU discharge. AKI was diagnosed and staged using sCr according to Kidney Disease Improving Global Outcomes (KDIGO) definitions. Urine samples were collected at hospital admission (before surgery), at ICU admission, 12 and 24h after ICU admission. Urinary biomarkers clusterin, calbindin, pi-glutathione S-transferase; interleucin 18 (IL-18), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1); microalbumin, beta-2-microglobulin, cistatin C, neutrophil gelatinase associated lipocalin (NGAL), osteopontin (OPN), trefoil factor 3, tissue inhibitor of metalloproteinase-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP-7) were assessed by Luminex x-MAP method. Data were tested for normality by Kolmogorov-Smirnov test, and are presented as median (first and third quartiles), mean ± standard deviation or frequency. The accuracy of ROC curves was assessed using non-AKI and AKI KDIGO I as control and AKI KDIGO II and III as positive result. We tested the biomarkers isolated and in different combinations to find the better accuracy. Statistical significance was p < 0.05. RESULTS: Patients\' median age was 56 ± 15 years, and 59% were female; hospital length of stay was 17.7 ± 16.2 days, ICU length of stay was 3.1 ± 2.9 days and 90 days mortality rate was 6.4%. A total of 71 patients (24%) developed AKI by KDIGO SCr criteria. The biomarkers MCP-1, IL-18, KIM-1, OPN, NGAL, TIMP-2 and IGFBP-7 were significantly higher for the AKI group on all time points analyzed. The product of MCP-1 and KIM-1 in the preoperative period achieved a good accuracy (AUC = 0.79; confidence interval 95% 0.69 - 0.88). The better time for AKI prediction was 12 hours after of ICU admission using the product of KIM-1, NGAL and TIMP-2 (AUC = 0.86; confidence interval 95% 0.79 - 0.94). These two biomarkers combinations presented higher accuracy than any of the biomarkers alone or in other combinations, and were associated to longer length of stay and 90 days mortality. CONCLUSIONS: Most of patients who developed moderate or severe AKI presented high levels of BM at hospitalization (before surgery) and the product of MCP-1 and KIM-1 showed good prediction accuracy for AKI. The best prediction accuracy for moderate or severe AKI was the product of KIM-1, NGAL and TIMP-2, 12 hours after ICU admission. Any of the two BMs combinations presented higher accuracy than the BM tested alone (AU)

FAPESP's process: 17/06332-6 - Predictive potential of urinary biomarkers for early diagnosis of acute kidney injury in relevant clinically situations
Grantee:Lia Junqueira Marçal
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)