SLPI - a Biomarker of Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm (TAAA) Repair

Abstract

Acute kidney injury (AKi) is a relevant complication following thoracoabdominal aortic aneurysm repair (tAAA). Biomarkers, such as secretory leucocyte peptidase inhibitor (SLpi), may enable a more accurate diagnosis. in this study, we tested if SLpi measured in serum is an appropriate biomarker of AKi after TAAA repair. In a prospective observational single-center study including 33 patients (51.5% women, mean age 63.0 ± 16.2 years) undergoing open and endovascular aortic aneurysm repair in 2017, SLPI was measured peri-operatively (until 72 h after surgery). After surgery, the postoperative complications AKI, as defined according to the KDIGO diagnostic criteria, sepsis, death, MACE (major cardiovascular events) and, pneumonia were assessed. in a subgroup analysis, patients with preexisting kidney disease were excluded. Of 33 patients, 51.5% (n = 17) of patients developed AKI. Twelve hours after admission to the intensive care unit (ICU), SLPI serum levels were significantly increased in patients who developed AKI. Multivariable logistic regression revealed a significant association between SLPI 12 hours after admission to ICU and AKI (P = 0.0181, OR = 1.055, 95% CI = 1.009-1.103). The sensitivity of SLPI for AKI prediction was 76.47% (95% CI = 50.1-93.2) and the specificity was 87.5% (95% CI = 61.7-98.4) with an AUC = 0.838 (95% CI = 0.7-0.976) for an optimal cut-off 70.03 ng/ml 12 hours after surgery. in patients without pre-existing impaired renal function, an improved diagnostic quality of SLpi for AKI was observed (Sensitivities of 45.45-91.67%, Specificities of 77.7-100%, AUC = 0.716-0.932). there was no association between perioperative SLpi and the incidence of sepsis, death, MAce (major cardiovascular events), pneumonia. this study suggests that SLpi might be a post-operative biomarker of AKi after tAAA repair, with a superior diagnostic accuracy for patients without preexisting impaired renal function.Open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is related to a high risk of postoperative complications. With an incidence ranging between 13 and 42%, acute kidney injury (AKI) is one of the most common complications and closely associated with increased mortality and cardiovascular morbidity 1-3 . The early detection of impaired kidney function and other organ dysfunctions may enable an immediate start of specific treatment bundles. The diagnosis of AKI is mainly based on patients' urine output and serum creatinine levels. Serum creatinine is an established, yet controversial biomarker due to its delayed increase and low sensitivity for the detection of an impaired kidney function 4-6 . In this context, the necessity of clinically available early and reliable biomarkers of AKI becomes evident.Secretory leucocyte peptidase inhibitor (SLPI) is a protease inhibitor and regulator of innate and adaptive immunity 7 . It is synthesized predominantly in immune and epithelial cells of mucosal surfaces, such as the pancreas and kidney 8 . Elevated serum SLPI levels have been observed in acu...

The Role of Ribonuclease 1 and Ribonuclease Inhibitor 1 in Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm Repair

“…The trial is registered under the ClinicalTrials.gov number NCT03093857. The cohort of patients has been previously described in a recently published study [ 15 ].…”

Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

“…MIF-2 improved the recovery of injured epithelial cells by enhancing cell regeneration through secretory leukocyte proteinase inhibitor (SLPI) and activating transcription factor (ATF) 4-dependent mechanisms (83). SLPI has proliferative, antioxidant and cytoprotective properties, and is being evaluated as a biomarker for AKI after surgery (84)(85)(86).…”

Potent Therapy and Transcriptional Profile of Combined Erythropoietin-Derived Peptide Cyclic Helix B Surface Peptide and Caspase-3 siRNA against Kidney Ischemia/Reperfusion Injury in Mice

“…SLPI, secretory leukocyte peptidase inhibitor，among the top 5 DEGs up-regulated by CASP3 siRNA (Table 3), was renoprotective in experimental ischemia AKI (Ochi et al, 2017). SLPI inhibits nuclear factor kappa beta (NF-κB) signaling pathway (Tang et al, 2020) and the maturation of IL-1β (Zakrzewicz et al, 2019), and showed as a biomarker candidate in AKI (Averdunk et al, 2019;Averdunk et al, 2020). In human, SERPINA3, a member of the serpin superfamily of protease inhibitors, could limit inflammation by targeting cathepsin family (proinflammatory enzymes) (Horvath et al, 2005;Lannan et al, 2012).…”