Kidney Week Educational Symposia-Advances in Inflammation Mechanisms and Therapies to Reduce Atherosclerotic Cardiovascular Disease in Persons with Kidney Diseases

Video Transcription

Video Summary

The symposium reviews how chronic systemic inflammation drives atherosclerotic cardiovascular disease (ASCVD) in chronic kidney disease (CKD) and emerging anti-inflammatory treatments. The introduction contrasts chronic vs acute inflammation and notes common drivers (obesity, inactivity, diet, dysbiosis, poor sleep) and consequences (end-organ damage including CKD and cardiovascular disease). CKD strongly associates with inflammation (often tracked by hsCRP), which rises as eGFR declines and predicts cardiovascular mortality; traditional lipid-lowering therapies show diminishing benefit in advanced CKD/dialysis, motivating new strategies.<br /><br />Dr. Stephen Crowley summarizes evidence that inflammatory mediators (e.g., IL‑6, TNF, GDF15, ST2) predict vascular events in CKD cohorts. Mechanistically, CKD increases damage-associated molecular patterns (DAMPs) that activate monocytes/macrophages, promoting foam-cell formation, oxidative stress, and cytokine production. He argues inflammation also worsens hypertension by increasing renal sodium retention through cytokine effects on tubular transporters, creating a feedback loop where sodium retention further promotes pro-inflammatory immune polarization.<br /><br />Dr. Laura Dember focuses on anti-cytokine therapies, emphasizing IL‑1/IL‑6 pathways. Small CKD/ESKD trials of IL‑1 blockade (rilonacept, anakinra) modestly lowered CRP/IL‑6; IL‑6 antibodies (ziltivekimab) produced strong, dose-dependent CRP suppression and improved anemia parameters in dialysis. Two large IL‑6 outcome trials are underway (CKD and dialysis). Safety monitoring centers on infections, cytopenias, and bowel perforation (anti‑IL‑6). Colchicine shows cardiovascular benefit in non-CKD populations but needs CKD-specific evaluation due to renal clearance concerns.

Asset Subtitle

Moderator(s): Michel Chonchol

Presentation(s):

Introduction - Michel Chonchol
Inflammation as a Mechanism for ASCVD in Kidney Diseases - Steven Crowley
Advances in Therapies to Target Inflammation to Reduce Atherosclerosis in Kidney Diseases - Laura Dember

Support is provided by an educational grant from Novo Nordisk.

Meta Tag

Date 10/25/2024

Pathway 1 Hypertension and Cardiorenal Disorders

Pathway 2 CKD Non-Dialysis

Session ID 493158

Session Type ES - Educational Symposium

Keywords

chronic systemic inflammation

atherosclerotic cardiovascular disease (ASCVD)

chronic kidney disease (CKD)

high-sensitivity C-reactive protein (hsCRP)

IL-6 pathway

IL-1 blockade (anakinra, rilonacept)

ziltivekimab

DAMPs and monocyte/macrophage activation

dialysis/ESKD anti-inflammatory outcome trials