Kidney Week 2025 Annual Meeting-Role of the Immune System in CKD

Video Transcription

Video Summary

This recorded ASN session, chaired by Carmen De Miguel and LaTanya Hickson, focused on how immune and inflammatory pathways drive kidney disease and related cardio-renal complications in CKD.<br /><br />Radha Alisic reviewed the kidney’s resident immune network (myeloid and lymphoid cells) and its tight crosstalk with parenchymal cells (endothelium, podocytes, mesenchyme) through chemokines/cytokines and inflammasomes. She summarized immune mechanisms across major glomerular diseases: ANCA vasculitis (Th1/Th17 pathways; IL-12/23 and IL-17 signatures suggesting targeted therapy), IgA nephropathy (APRIL/BAFF-driven B-cell biology and the “four-hit” model, plus complement involvement), lupus nephritis immune polarization, and podocyte autoimmunity (anti-nephrin antibodies in some minimal change disease; multiple podocyte antigens in membranous nephropathy). She emphasized that diabetic kidney disease (DKD) is not purely hemodynamic: hyperglycemia triggers RAGE, TLR2/4, NF-κB, JAK-STAT, oxidative stress, and NLRP3 inflammasome activation, with immune-cell infiltration and structural damage. She noted mixed results of prior anti-inflammatory trials and highlighted emerging IL-1β/IL-6 targeting and possible GLP-1 receptor agonist anti-inflammatory effects.<br /><br />Yiming Zhou centered on macrophage heterogeneity/polarization and presented single-cell and mechanistic work identifying TREM2+ lipid-associated macrophages as protective in DKD and AKI-to-CKD transition via PI3K-AKT signaling; adoptive transfer of TREM2-overexpressing macrophages reduced fibrosis in mice. In lupus nephritis, he implicated M2B-like macrophages in progression and described mannose-targeted selenium nanoparticles that suppressed M2B activation (via JAK/STAT) and improved lupus phenotypes in mice. He also outlined manganese nanoparticle strategies to reprogram tumor-associated macrophages in renal cancer.<br /><br />Joshua Thurman explained complement activation in CKD, highlighting the alternative pathway’s special susceptibility in kidneys, distinct glomerular vs tubular-interstitial activation mechanisms (injury, proteinuria, ammonia, and local tubular C3 production), and rising factor D/alternative activation markers as GFR declines—suggesting a potential vicious cycle and therapeutic opportunities, tempered by long-term risk/benefit concerns.<br /><br />Marta Ruiz-Ortega discussed anti-inflammatory treatment strategies and how standard therapies (RAAS blockade, SGLT2 inhibitors, GLP-1 agonists) intersect with immune signaling (NF-κB, JAK-STAT). She highlighted IL-17/Th17 and IL-6 as potential targets, links between inflammation and tubular senescence (“SASP”), and epigenetic approaches (BET/bromodomain inhibitors) that suppress NF-κB-driven transcription and Th17 differentiation. She also noted emerging evidence that SGLT2-related benefits may involve epigenetic/metabolic reprogramming.

Asset Subtitle

Moderator(s): Carmen De Miguel, LaTonya Hickson

Presentation(s):

Inflammation in Diabetic and Nondiabetic Kidney Diseases: An Underrecognized Phenomenon - Radica Alicic
Macrophages at the Center of Diabetic Kidney Disease - Yiming Zhou
Role of Complement Activation in CKD - Joshua Thurman
Targeting Inflammation and the Immune System for Treatment of CKD - Marta Ruiz-Ortega

Meta Tag

Date 11/7/2025

Pathway 1 CKD Non-Dialysis

Pathway 2 Diabetic Kidney Disease

Session ID 507256

Keywords

chronic kidney disease (CKD)

immune-inflammatory pathways

kidney resident immune cells

chemokines and cytokines

inflammasome (NLRP3)

diabetic kidney disease (DKD) inflammation

macrophage polarization and heterogeneity

TREM2+ lipid-associated macrophages

AKI-to-CKD transition and fibrosis

lupus nephritis immune mechanisms

IgA nephropathy APRIL/BAFF

ANCA-associated vasculitis Th17 IL-17

complement alternative pathway factor D

NF-κB and JAK-STAT signaling

SGLT2 inhibitors and GLP-1 receptor agonists