nach oben

Erschienen in:

20.01.2024 | Original Article

VWF/ADAMTS13 Ratio as a Potential Predictive Biomarker for Acute Kidney Injury Onset in Cirrhosis

verfasst von: Shohei Asada, Tadashi Namisaki, Kosuke Kaji, Hiroaki Takaya, Takahiro Kubo, Takemi Akahane, Hideto Kawaratani, Norihisa Nishimura, Soichi Takeda, Hiroyuki Masuda, Akihiko Shibamoto, Takashi Inoue, Satoshi Iwai, Fumimasa Tomooka, Yuki Tsuji, Yukihisa Fujinaga, Koh Kitagawa, Akira Mitoro, Shinya Sato, Masanori Matsumoto, Hitoshi Yoshiji

Erschienen in: Digestive Diseases and Sciences | Ausgabe 3/2024

Einloggen, um Zugang zu erhalten

Abstract

Aim

We investigated the von Willebrand factor to ADAMTS13 ratio (von Willebrand factor [VWF]:Ag/ADAMTS13:AC) as a potential biomarker for the outcomes of acute kidney injury (AKI) in liver cirrhosis (LC).

Methods

This retrospective cross-sectional study included patients with LC who developed AKI (AKI group: n = 91) and patients with LC who did not develop AKI [non-AKI (NAKI) group, n = 91] as a control group. Plasma levels of the von Willebrand factor antigen (Ag) and ADAMTS13 activity (AC) were measured in patients with AKI or NAKI. Moreover, risk factors for onset of AKI, AKI-associated 90-day mortality, and poor AKI treatment response were identified.

Results

The AKI group had a significantly higher VWF:Ag/ADAMTS13:AC than the NAKI group. Values of VWF:Ag/ADAMTS13:AC ≥ 5.7 were identified as risk factors for AKI onset in patients with LC (odds ratio [OR] 2.56; 95% CI 1.26–4.99; p < 0.001). Among patients with AKI, values of VWF:Ag/ADAMTS13:AC ≥ 9.0 were identified as risk factors for 90-day mortality (OR 6.83; 95% CI 2.32–20.10; p < 0.001). Cumulative survival was significantly lower in those with high (≥ 9.0) than in those with low (< 9.0) VWF:Ag/ADAMTS13:AC. Furthermore, values of VWF:Ag/ADAMTS13:AC ≥ 7.4 were identified as risk factors for poor treatment response (OR 4.2; 95% CI 1.39–12.70; p < 0.001). The treatment response rates were significantly higher in those with low (< 7.4) VWF:Ag/ADAMTS13:AC than in those with high (≥ 7.4) VWF:Ag/ADAMTS13:AC.

Conclusion

VWF:Ag/ADAMTS13:AC potentially predicts the onset, prognosis, and treatment response of AKI in patients with LC.

Allegretti AS, Parada XV, Endres P et al. Urinary NGAL as a diagnostic and prognostic marker for acute kidney injury in cirrhosis: a prospective study. Clin Transl Gastroenterol 2021;12:e00359.PubMedPubMedCentralCrossRef

Ng CK, Chan MH, Tai MH et al. Hepatorenal syndrome. Clin Biochem Rev 2007;28:11–17.PubMedPubMedCentral

European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69:406–460.

Garcia-Tsao G, Parikh CR, Viola A. Acute kidney injury in cirrhosis. Hepatology. 2008;48:2064–2077.PubMedCrossRef

Tariq R, Hadi Y, Chahal K et al. Incidence, mortality and predictors of acute kidney injury in patients with cirrhosis: a systematic review and meta-analysis. J Clin Transl Hepatol. 2020;8:135–142.PubMedPubMedCentralCrossRef

Patidar KR, Naved MA, Grama A et al. Acute kidney disease is common and associated with poor outcomes in patients with cirrhosis and acute kidney injury. J Hepatol. 2022;77:108–115.PubMedCrossRef

Runyon BA. Introduction to the revised American Association for the Study of Liver Diseases Practice Guideline management of adult patients with ascites due to cirrhosis. Hepatology. 2013;57:1651–3.PubMedCrossRef

Karagozian R, Bhardwaj G, Wakefield DB et al. Acute kidney injury is associated with higher mortality and healthcare costs in hospitalized patients with cirrhosis. Ann Hepatol. 2019;18:730–735.PubMedCrossRef

Scott RA, Austin AS, Kolhe NV et al. Acute kidney injury is independently associated with death in patients with cirrhosis. Frontline Gastroenterol. 2013;4:191–197.PubMedPubMedCentralCrossRef

10.

Angeli P, Gines P, Wong F et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62:968–974.PubMedCrossRef

11.

12.

Cullaro G, Park M, Lai JC. “Normal” creatinine levels predict persistent kidney injury and waitlist mortality in outpatients with cirrhosis. Hepatology. 2018;68:1953–1960.PubMedCrossRef

13.

Salerno F, Guevara M, Bernardi M et al. Refractory ascites: pathogenesis, definition and therapy of a severe complication in patients with cirrhosis. Liver Int. 2010;30:937–947.PubMedCrossRef

14.

Wong F. Recent advances in our understanding of hepatorenal syndrome. Nat Rev Gastroenterol Hepatol. 2012;9:382–391.PubMedCrossRef

15.

Soejima K, Matsumoto M, Kokame K et al. ADAMTS-13 cysteine-rich/spacer domains are functionally essential for von Willebrand factor cleavage. Blood. 2003;102:3232–3237.PubMedCrossRef

16.

Akyol O, Akyol S, Chen C-H. Update on ADAMTS13 and VWF in cardiovascular and hematological disorders. Clinica Chimica Acta. 2016;463:109–118.CrossRef

17.

Uemura M, Fujimura Y, Matsumoto M et al. Comprehensive analysis of ADAMTS13 in patients with liver cirrhosis. Thromb Haemost. 2008;99:1019–1029.PubMedCrossRef

18.

Takaya H, Namisaki T, Asada S et al. ADAMTS13, VWF, and endotoxin are interrelated and associated with the severity of liver cirrhosis via hypercoagulability. J Clin Med. 2022;11:1835.PubMedPubMedCentralCrossRef

19.

Simbrunner B, Villesen IF, Scheiner B et al. Von Willebrand factor processing in patients with advanced chronic liver disease and its relation to portal hypertension and clinical outcome. Hepatol Int. 2023;17:1532–1544.PubMedCrossRef

20.

Takaya H, Namisaki T, Enomoto M et al. The ratio of von Willebrand factor antigen to ADAMTS13 activity: usefulness as a prognostic biomarker in acute-on-chronic liver failure. Biology. 2023;12:164.PubMedPubMedCentralCrossRef

21.

Sedaghat S, de Vries PS, Boender J et al. von Willebrand factor, ADAMTS13 activity, and decline in kidney function: a population-based cohort study. Am J Kidney Dis. 2016;68:726–732.PubMedCrossRef

22.

Tsai HM. Mechanisms of microvascular thrombosis in thrombotic thrombocytopenic purpura. Kidney Int Suppl. 2009;75:S11–S14.CrossRef

23.

Hametner S, Ferlitsch A, Ferlitsch M et al. The VITRO score (Von Willebrand Factor Antigen/Thrombocyte Ratio) as a new marker for clinically significant portal hypertension in comparison to other non-invasive parameters of fibrosis including ELF test. PLoS ONE. 2016;11:e0149230.PubMedPubMedCentralCrossRef

24.

Yewale RV, Ramakrishna BS. Novel biomarkers of acute kidney injury in chronic liver disease: where do we stand after a decade of research? Hepatol Res. 2023;53:3–17.PubMedCrossRef

25.

Lee HA, Seo YS. Current knowledge about biomarkers of acute kidney injury in liver cirrhosis. Clin Mol Hepatol. 2022;28:31–46.PubMedCrossRef

26.

European Association for the Study of the Liver. Electronic address eee, European Association for the Study of the L. Corrigendum to “EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis”. J Hepatol 2018;69:1207.

27.

Yoshiji H, Nagoshi S, Akahane T et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol. 2021;56:593–619.PubMedPubMedCentralCrossRef

28.

Yoshiji H, Nagoshi S, Akahane T et al. Evidence-based clinical practice guidelines for liver cirrhosis 2020. Hepatol Res. 2021;51:725–749.PubMedCrossRef

29.

Crabb DW, Im GY, Szabo G et al. Diagnosis and treatment of alcohol-associated liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71:306–333.PubMedCrossRef

30.

Henry BM, Benoit SW, de Oliveira MHS et al. ADAMTS13 activity to von Willebrand factor antigen ratio predicts acute kidney injury in patients with COVID-19: evidence of SARS-CoV-2 induced secondary thrombotic microangiopathy. Int J Lab Hematol. 2021;43:129–136.PubMedCrossRef

31.

Tahata Y, Sakamori R, Maesaka K et al. Effect of sofosbuvir and velpatasvir therapy on clinical outcome in hepatitis C virus patients with decompensated cirrhosis. Hepatol Res. 2023;53:301–311.PubMedCrossRef

32.

Maesaka K, Sakamori R, Yamada R et al. Clinical course of hepatitis C virus-positive patients with decompensated liver cirrhosis in the era of direct-acting antiviral treatment. Hepatol Res. 2021;51:517–527.PubMedCrossRef

33.

Shibamoto A, Namisaki T, Suzuki J, et al. Hemoglobin levels as a surrogate marker of sarcopenia in patients with liver cirrhosis. Hepatol Res. 2023.

34.

Kato S, Matsumoto M, Matsuyama T et al. Novel monoclonal antibody-based enzyme immunoassay for determining plasma levels of ADAMTS13 activity. Transfusion. 2006;46:1444–1452.PubMedCrossRef

35.

Matsumoto M, Kawaguchi S, Ishizashi H et al. Platelets treated with ticlopidine are less reactive to unusually large von Willebrand factor multimers than are those treated with aspirin under high shear stress. Pathophysiol Haemost Thromb. 2005;34:35–40.PubMedCrossRef

36.

Jung CY, Chang JW. Hepatorenal syndrome: current concepts and future perspectives. Clin Mol Hepatol. 2023.

37.

Chaney A. A Review for the practicing clinician: hepatorenal syndrome, a form of acute kidney injury, in patients with cirrhosis. Clin Exp Gastroenterol. 2021;14:385–396.PubMedPubMedCentralCrossRef

38.

Gracia-Sancho J, Marrone G, Fernandez-Iglesias A. Hepatic microcirculation and mechanisms of portal hypertension. Nat Rev Gastroenterol Hepatol. 2019;16:221–234.PubMedCrossRef

39.

Takaya H, Uemura M, Fujimura Y et al. ADAMTS13 activity may predict the cumulative survival of patients with liver cirrhosis in comparison with the Child-Turcotte-Pugh score and the Model for End-Stage Liver Disease score. Hepatol Res. 2012;42:459–472.PubMedCrossRef

40.

Uemura M, Fujimura Y, Ko S et al. Determination of ADAMTS13 and its clinical significance for ADAMTS13 supplementation therapy to improve the survival of patients with decompensated liver cirrhosis. Int J Hepatol. 2011;2011:759047.PubMedPubMedCentralCrossRef

41.

Hugenholtz GC, Adelmeijer J, Meijers JC et al. An unbalance between von Willebrand factor and ADAMTS13 in acute liver failure: implications for hemostasis and clinical outcome. Hepatology. 2013;58:752–761.PubMedCrossRef

42.

Enomoto M, Takaya H, Namisaki T et al. Ratio of von Willebrand factor antigen to ADAMTS13 activity is a useful biomarker for acute-on-chronic liver failure development and prognosis in patients with liver cirrhosis. Hepatol Res. 2022;52:390–400.PubMedCrossRef

43.

Jiang QQ, Han MF, Ma K et al. Acute kidney injury in acute-on-chronic liver failure is different from in decompensated cirrhosis. World J Gastroenterol. 2018;24:2300–2310.PubMedPubMedCentralCrossRef

44.

Makris K, Spanou L. Acute kidney injury: definition, pathophysiology and clinical phenotypes. Clin Biochem Rev. 2016;37:85–98.PubMedPubMedCentral

45.

Wang Y, Liu LP, Bai WY et al. Renal haemodynamics in patients with liver cirrhosis assessed by colour ultrasonography. J Int Med Res. 2011;39:249–255.PubMedCrossRef

46.

Ring-Larsen H. Renal blood flow in cirrhosis: relation to systemic and portal haemodynamics and liver function. Scand J Clin Lab Invest. 1977;37:635–642.PubMedCrossRef

47.

Plautz WE, Haldeman SH, Dyer MR et al. Reduced cleavage of von willebrand factor by ADAMTS13 is associated with microangiopathic acute kidney injury following trauma. Blood Coagul Fibrinolysis. 2022;33:14–24.PubMedCrossRef

48.

Scheiner B, Balcar L, Nussbaumer RJ et al. Factor VIII/protein C ratio independently predicts liver-related events but does not indicate a hypercoagulable state in ACLD. J Hepatol. 2022;76:1090–1099.PubMedCrossRef

49.

Amin AA, Alabsawy EI, Jalan R et al. Epidemiology, pathophysiology, and management of hepatorenal syndrome. Semin Nephrol. 2019;39:17–30.PubMedCrossRef

Titel: VWF/ADAMTS13 Ratio as a Potential Predictive Biomarker for Acute Kidney Injury Onset in Cirrhosis
verfasst von: Shohei Asada
Tadashi Namisaki
Kosuke Kaji
Hiroaki Takaya
Takahiro Kubo
Takemi Akahane
Hideto Kawaratani
Norihisa Nishimura
Soichi Takeda
Hiroyuki Masuda
Akihiko Shibamoto
Takashi Inoue
Satoshi Iwai
Fumimasa Tomooka
Yuki Tsuji
Yukihisa Fujinaga
Koh Kitagawa
Akira Mitoro
Shinya Sato
Masanori Matsumoto
Hitoshi Yoshiji
Publikationsdatum: 20.01.2024
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 3/2024
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-023-08257-w

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Herzinfarkt mit 85 – trotzdem noch intensive Lipidsenkung?

16.05.2024 Hypercholesterinämie Nachrichten

Profitieren nach einem akuten Myokardinfarkt auch Betroffene über 80 Jahre noch von einer intensiven Lipidsenkung zur Sekundärprävention? Um diese Frage zu beantworten, wurden jetzt Registerdaten aus Frankreich ausgewertet.

Erstmanifestation eines Diabetes-Typ-1 bei Kindern: Ein Notfall!

16.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Manifestiert sich ein Typ-1-Diabetes bei Kindern, ist das ein Notfall – ebenso wie eine diabetische Ketoazidose. Die Grundsäulen der Therapie bestehen aus Rehydratation, Insulin und Kaliumgabe. Insulin ist das Medikament der Wahl zur Behandlung der Ketoazidose.

CKD bei Diabetes: Neuheiten und Zukunftsaussichten

16.05.2024 DDG-Jahrestagung 2024 Kongressbericht

Jeder Mensch mit Diabetes muss auf eine chronische Nierenerkrankung gescreent werden – diese neue Empfehlung spricht die KDIGO aus. Die Therapie erfolgt individuell und je nach Szenario mit verschiedenen Substanzklassen. Künftig kommt wahrscheinlich, neben RAS-Hemmung, SGLT2-Inhibition und nsMRA, eine vierte Therapiesäule hinzu.

Riesenzellarteriitis: 15% der Patienten sind von okkulter Form betroffen

16.05.2024 Riesenzellarteriitis Nachrichten

In einer retrospektiven Untersuchung haben Forschende aus Belgien und den Niederlanden die okkulte Form der Riesenzellarteriitis genauer unter die Lupe genommen. In puncto Therapie und Rezidivraten stellten sie keinen sehr großen Unterschied zu Erkrankten mit kranialen Symptomen fest.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Aim

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2024

l-Menthol for Color Difference Change Between Early Gastric Cancer and Surrounding Mucosa: A Prospective Study

Planned Hybrid Endoscopic Submucosal Dissection as Alternative for Colorectal Neoplasms: A Propensity Score-Matched Study

Predictors of Subsequent Celiac Disease Seropositivity in Patients Diagnosed with Duodenal Villus Atrophy on Upper Endoscopy

SOX4/HDAC2 Axis Enhances Cell Survivability and Reduces Apoptosis by Activating AKT/MAPK Signaling in Colorectal Cancer

Nurse Supervised at Institutes versus Nurse Counseling Home-Based Resistance Exercise Training for Acute Pancreatitis