Early prediction of acute kidney injury after transapical and transaortic aortic valve implantation with urinary G1 cell cycle arrest biomarkers.
Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) leading to increased mortality and morbidity. Urinary G1 cell cycle arrest proteins TIMP-2 and IGFBP7 have recently been suggested as sensitive biomarkers for early detection of AKI in critically ill patients. However, the precise role of urinary TIMP-2 and IGFBP7 in patients undergoing TAVI is unknown.



In a prospective observational trial, 40 patients undergoing TAVI (either transaortic or transapical) were enrolled. Serial measurements of TIMP-2 and IGFBP7 were performed in the early post interventional course. The primary clinical endpoint was the occurrence of AKI stage 2/3 according to the KDIGO classification.



Now we show, that ROC analyses of [TIMP-2]*[IGFBP7] on day one after TAVI reveals a sensitivity of 100 % and a specificity of 90 % for predicting AKI 2/3 (AUC 0.971, 95 % CI 0.914-1.0, SE 0.0299, p = 0.001, cut-off 1.03). In contrast, preoperative and postoperative serum creatinine levels as well as glomerular filtration rate (GFR) and perioperative change in GFR did not show any association with the development of AKI. Furthermore, [TIMP-2]*[IGFBP7] remained stable in patients with AKI ≤1, but its levels increased significantly as early as 24 h after TAVI in patients who developed AKI 2/3 in the further course (4.77 ± 3.21 vs. 0.48 ± 0.68, p = 0.022). Mean patients age was 81.2 ± 5.6 years, 16 patients were male (40.0 %). 35 patients underwent transapical and five patients transaortic TAVI. 15 patients (37.5 %) developed any kind of AKI; eight patients (20 %) met the primary endpoint and seven patients required renal replacement therapy (RRT) within 72 h after surgery.



Early elevation of urinary cell cycle arrest biomarkers after TAVI is associated with the development of postoperative AKI. [TIMP-2]*[IGFBP7] provides an excellent diagnostic accuracy in the prediction of AKI that is superior to that of serum creatinine.
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany. Fabian.dusse@uk-essen.de.|Department of Anesthesiology and Intensive Care Medicine, Medical Center Cologne-Merheim, University of Witten/Herdecke, Ostmerheimerstrasse 200, 51109, Cologne, Germany. Fabian.dusse@uk-essen.de.
Fabian
F
Dusse
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.|Klinik für Anästhesiologie und Intensivmedizin, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
Michaela
M
Edayadiyil-Dudásova
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
Matthias
M
Thielmann
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
Daniel
D
Wendt
Department of Cardiology, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
Philipp
P
Kahlert
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
Ender
E
Demircioglu
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.
Heinz
H
Jakob
Klinik für Anästhesiologie und Intensivmedizin, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.|Klinik für Anästhesiologie, Ludwig-Maximilians Universität München, Marchioninistraße 15, 81377, Munich, Germany.
Simon T
ST
Schaefer
Department of Thoracic and Cardiovascular Surgery, West German Heart and Vascular Center Essen, University Hospital Essen, Hufelandstraße 55, 45122, Essen, Germany.|Department of Intensive Care Medicine, Imland-Klinik Rendsburg, Lilienstraße 20-28, 24768, Rendsburg, Germany.
Kevin
K
Pilarczyk
D058186:Acute Kidney Injury / Q000097:blood / Q000175:diagnosis* / Q000209:etiology* / Q000652:urine; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000097:blood; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D005919:Glomerular Filtration Rate; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000652:urine*; D008297:Male; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000652:urine*
D015415:Biomarkers; D018969:Insulin-Like Growth Factor Binding Proteins; C560823:TIMP2 protein, human; C102529:insulin-like growth factor binding protein-related protein 1; D019716:Tissue Inhibitor of Metalloproteinase-2; D003404:Creatinine
AKI; Acute kidney injury; Biomarker; Cell cycle arrest; IGFBP7; NephroCheck; TAVI; TAVR; TIMP-2