Anti-inflammatorische Therapie in CKD - ZEUS - Prof. Dr. Dr. Thimoteus Speer (Frankfurt am Main)

Prof. Dr. Dr. Thimoteus Speer erläutert die Bedeutung inflammatorischer Signalkaskaden für das hohe kardiovaskuläre Risiko von Patienten mit chronischer Nierenkrankung - und zeigt auf, wie der IL-6 Inhibitor Ziltivekimab, der aktuell in der ZEUS Studie untersucht wird, das kardiovaskuläre Risiko bei nierenkranken Menschen reduzieren könnte.
Prof. Dr. Dr. Thimoteus Speer ist Ordinarius für Nephrologie an der Goethe-Universität Frankfurt am Main und Direktor der Klinik für Nephrologie des Universitätsklinikum Frankfurt.


Das Gespräch wurde am 20.06.2023 geführt. Moderatoren: Prof. Dr. Dominique Guerrot (Rouen, France), Prof. Dr. Dr. Stephan Schirmer (Kaiserslautern, Deutschland) und Prof. Dr. Gunnar Heine (Frankfurt am Main, Deutschland).

Weitere Literatur:

From RESCUE to ZEUS: will interleukin-6 inhibition with ziltivekimab prove effective for cardiovascular event reduction?
Ridker PM.
Cardiovasc Res. 2021
doi: 10.1093/cvr/cvab231.

Low-Dose Methotrexate for the Prevention of Atherosclerotic Events.
Ridker PM, Everett BM, Pradhan A, MacFadyen JG, Solomon DH, Zaharris E, Mam V, Hasan A, Rosenberg Y, Iturriaga E, Gupta M, Tsigoulis M, Verma S, Clearfield M, Libby P, Goldhaber SZ, Seagle R, Ofori C, Saklayen M, Butman S, Singh N, Le May M, Bertrand O, Johnston J, Paynter NP, Glynn RJ; CIRT Investigators.
N Engl J Med. 2019
doi: 10.1056/NEJMoa1809798

IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial.
Ridker PM, Devalaraja M, Baeres FMM, Engelmann MDM, Hovingh GK, Ivkovic M, Lo L, Kling D, Pergola P, Raj D, Libby P, Davidson M; RESCUE Investigators.
Lancet. 2021
doi: 10.1016/S0140-6736(21)00520-1

The heart and vascular system in dialysis.
Wanner C, Amann K, Shoji T.
Lancet. 2016
doi: 10.1016/S0140-6736(16)30508-6

Inhibition of Interleukin-1β by Canakinumab and Cardiovascular Outcomes in Patients With Chronic Kidney Disease.
Ridker PM, MacFadyen JG, Glynn RJ, Koenig W, Libby P, Everett BM, Lefkowitz M, Thuren T, Cornel JH.
J Am Coll Cardiol. 2018
doi: 10.1016/j.jacc.2018.03.490.

Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.
Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, Ritz E; German Diabetes and Dialysis Study Investigators.
N Engl J Med. 2005
doi: 10.1056/NEJMoa043545

IL-1 Inhibition and Vascular Function in CKD.
Nowak KL et al.
J Am Soc Nephrol. 2017 doi: 10.1681/ASN.2016040453.

Interleukin-1α Is a Central Regulator of Leukocyte-Endothelial Adhesion in Myocardial Infarction and in Chronic Kidney Disease.
Schunk SJ, ..., Speer T.
Circulation 2021
doi: 10.1161/CIRCULATIONAHA.121.053547

Residual inflammatory risk associated with interleukin-18 and interleukin-6 after successful interleukin-1β inhibition with canakinumab: further rationale for the development of targeted anti-cytokine therapies for the treatment of atherothrombosis.
Ridker PM, MacFadyen JG, Thuren T, Libby P.
Eur Heart J. 2020
doi: 10.1093/eurheartj/ehz542.

Empagliflozin in Patients with Chronic Kidney Disease.
The EMPA-KIDNEY Collaborative Group; Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R.
N Engl J Med. 2023
doi: 10.1056/NEJMoa2204233

Abnormal high-density lipoprotein induces endothelial dysfunction via activation of Toll-like receptor-2.
Speer T, Rohrer L, Blyszczuk P, Shroff R, Kuschnerus K, Kränkel N, Kania G, Zewinger S, Akhmedov A, Shi Y, Martin T, Perisa D, Winnik S, Müller MF, Sester U, Wernicke G, Jung A, Gutteck U, Eriksson U, Geisel J, Deanfield J, von Eckardstein A, Lüscher TF, Fliser D, Bahlmann FH, Landmesser U.
Immunity. 2013
doi: 10.1016/j.immuni.2013.02.009

IL-1 Inhibition and Function of the HDL-Containing Fraction of Plasma in Patients with Stages 3 to 5 CKD.
Hung AM, Tsuchida Y, Nowak KL, Sarkar S, Chonchol M, Whitfield V, Salas N, Dikalova A, Yancey PG, Huang J, Linton MF, Ikizler TA, Kon V.
Clin J Am Soc Nephrol. 2019
doi: 10.2215/CJN.04360418.

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.
Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group.
N Engl J Med. 2017
doi: 10.1056/NEJMoa1707914