Therapie der Inflammation in der Nephrologie

Was ist neu?

Low-Grade-Inflammation bei Nierenerkrankungen

Während Nierenerkrankungen, die mit akuter nicht infektiöser Entzündung einhergehen, wie bspw. Glomerulonephritiden, bereits seit Jahrzehnten erfolgreich primär antiinflammatorisch behandelt werden, ist die Low-Grade-Inflammation in der Nephrologie bisher noch wenig beachtet.

Antiinflammatorische Therapie in der Progressionshemmung

Nun rückt jedoch die pathophysiologische Bedeutung der chronischen systemischen Low-Grade-Inflammation für die Progression der chronischen Nierenerkrankung (CKD) und die damit verbundenen kardiovaskulären Komplikationen in den Vordergrund.

Antiinflammatorische Therapie der Atherosklerose

Antiinflammatorische Strategien haben in klinischen Studien bereits eine Effektivität in der Sekundär- und Tertiärprävention kardiovaskulärer Ereignisse gezeigt. Aktuelle Veröffentlichungen demonstrieren, dass eine Adressierung der Low-Grade-Inflammation mittels Inhibition der Interleukin-1- und Interleukin-6-Signalwege auch bei CKD-Patienten vorteilhafte Effekte auf die renale Anämie, die Progression der Nierenerkrankung sowie auf Komplikationsraten hat, ein todesursachenunabhängiger Mortalitätsvorteil zeigte sich jedoch bisher nicht.

Abstract

Pathophysiology of kidney diseases frequently implies sterile inflammation, e.g. during glomerulonephritis or after renal transplantation. Recently, the relevance of systemic low-grade inflammation for chronic kidney disease (CKD) progression and complications of CKD have come into focus. In this review article, the etiology, and consequences of low-grade inflammation in CKD patients are discussed. Further, the potential of anti-inflammatory approaches to slow down CKD progression is addressed. Recent advances have resulted in FDA approval of colchicine for patients with preserved renal function and atherosclerosis. Thus, lastly, anti-inflammatory therapy of atherosclerosis in patients with or without CKD is outlined.

Taken together, anti-inflammatory therapy offers novel opportunities to improve CKD progression, inhibit transition from acute to chronic kidney disease and reduce the risk of fatal long-term complications such as cardiovascular disease.

Schlüsselwörter

chronische Entzündung - Niere - CKD - Nephrologie - Kardiologie - Fortschreiten - Atherosklerose

Keywords

chronic inflammation - kidney - CKD - nephrology - cardiology - progression - atherosclerosis

Publication History

Article published online:
21 February 2025

• Literatur

• 1 Ren H, Lv W, Shang Z. et al. Identifying functional subtypes of IgA nephropathy based on three machine learning algorithms and WGCNA. BMC Med Genomics 2024; 17 (01) 61
• 2 Hengel FE, Dehde S, Lassé M. et al. Autoantibodies Targeting Nephrin in Podocytopathies. N Engl J Med 2024; 391 (05) 422-433
• 3 Guthridge JM, Wagner CA, James JA. The promise of precision medicine in rheumatology. Nat Med 2022; 28 (07) 1363-1371
• 4 Jankowski J, Floege J, Fliser D. et al. Cardiovascular Disease in Chronic Kidney Disease: Pathophysiological Insights and Therapeutic Options. Circulation 2021; 143 (11) 1157-1172
• 5 Pergola PE, Davidson M, Jensen C. et al. Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3–5: An Analysis of a Randomized Trial (RESCUE). J Am Soc Nephrol 2024; 35 (01) 74-84
• 6 Chertow GM, Chang AM, Felker GM. et al. IL-6 inhibition with clazakizumab in patients receiving maintenance dialysis: a randomized phase 2b trial. Nat Med 2024; 30 (08) 2328-2336
• 7 Dember LM, Hung A, Mehrotra R. et al. Hemodialysis Novel Therapies Consortium. A randomized controlled pilot trial of anakinra for hemodialysis inflammation. Kidney Int 2022; 102 (05) 1178-1187
• 8 Wang D, Naumova A, Isquith D. et al. Dapagliflozin Reduces Systemic Inflammation in Patients with Type 2 Diabetes Without Known Heart Failure. Res Sq [Preprint] 2024;
• 9 Platten M, Youssef S, Hur EM. et al. Blocking angiotensin-converting enzyme induces potent regulatory T cells and modulates TH1- and TH17-mediated autoimmunity. Proc Natl Acad Sci U S A 2009; 106 (35) 14948-14953
• 10 Katsuumi G, Shimizu I, Suda M. et al. SGLT2 inhibition eliminates senescent cells and alleviates pathological aging. Nat Aging 2024; 4 (07) 926-938
• 11 Lee SA, Riella LV. Narrative Review of Immunomodulatory and Anti-inflammatory Effects of Sodium-Glucose Cotransporter 2 Inhibitors: Unveiling Novel Therapeutic Frontiers. Kidney Int Rep 2024; 9 (06) 1601-1613
• 12 Perkovic V, Tuttle KR, Rossing P. et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med 2024; 391 (02) 109-121
• 13 Vlasschaert C, McNaughton AJM, Chong M. et al. Association of Clonal Hematopoiesis of Indeterminate Potenzial with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease. J Am Soc Nephrol 2022; 33 (05) 985-995
• 14 Kim HW, Joo YS, Yun HR. et al. Colchicine use and the risk of CKD progression: a multicentre nested case-control study. Rheumatology (Oxford) 2022; 61 (11) 4314-4323
• 15 Cho JM, Koh JH, Kim SG. et al. Mendelian randomization uncovers a protective effect of interleukin-1 receptor antagonist on kidney function. Commun Biol 2023; 6 (01) 722
• 16 Wen Y, Xu L, Melchinger I. et al. Longitudinal biomarkers and kidney disease progression after acute kidney injury. JCI Insight 2023; 8 (09) e167731
• 17 Ridker PM, Bhatt DL, Pradhan AD. et al. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: a collaborative analysis of three randomised trials. Lancet 2023; 401: 1293-1301
• 18 Nidorf SM, Fiolet ATL, Mosterd A. et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med 2020; 383 (19) 1838-1847
• 19 Tardif JC, Kouz S, Waters DD. et al. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med 2019; 381 (26) 2497-2505
• 20 Burger PM, Dorresteijn JAN, Fiolet ATL. et al. Individual lifetime benefit from low-dose colchicine in patients with chronic coronary artery disease. Eur J Prev Cardiol 2023; 30 (18) 1950-1962
• 21 Ridker PM, Everett BM, Thuren T. et al. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med 2017; 377 (12) 1119-1131
• 22 Ridker PM, MacFadyen JG, Glynn RJ. et al. Inhibition of Interleukin-1β by Canakinumab and Cardiovascular Outcomes in Patients With Chronic Kidney Disease. J Am Coll Cardiol 2018; 71 (21) 2405-2414