Kidney Week 2025 Annual Meeting-Immunity, Autoimmunity, and Hypertensive Kidney Damage

Video Transcription

Video Summary

The session explores how inflammation, immunity, and kidney sodium handling interact to drive hypertension, especially in chronic kidney disease (CKD) and autoimmune disease.<br /><br />Dr. Stephen Crowley described a bidirectional “vicious cycle” in CKD: impaired renal sodium excretion promotes hypertension, while inflammation further worsens sodium retention. Human cohort data (e.g., REGARDS, Framingham) link higher inflammatory cytokines (IL-1β, IL-6, TNF) with later development of hypertension and cardiovascular risk. Mechanistically, cytokines such as IL-17, IL-6, and IFN-γ increase renal sodium transporter activity (NHE3, NCC, ENaC). Crowley’s group showed kidney TNF and IL-1 signaling promote hypertension partly by suppressing nitric oxide in the thick ascending limb, enhancing NKCC2-mediated sodium retention. He also highlighted roles for dendritic-cell–mediated T-cell activation in hypertensive CKD, and the anti-inflammatory regulator A20 as a brake on this process. Loss of A20 in dendritic cells or renal tubules worsened hypertension via increased proximal-tubule NHE3, suggesting kidney-targeted A20 delivery (e.g., evolved AAV vectors) as a potential therapy.<br /><br />Dr. Keisa Mathis DeMasi focused on lupus (SLE), where immune activation and kidney inflammation precede early-onset hypertension. Using NZBWF1 lupus mice, she showed that stimulating the cholinergic anti-inflammatory pathway—especially with galantamine—reduced autoantibodies, inflammation, blood pressure, and renal injury, improving survival. More targeted neuromodulation approaches (brain DMV “DREADDs,” splenic ultrasound) showed anti-inflammatory and renal benefits, though blood-pressure effects were less consistent.<br /><br />Dr. David Harrison presented work identifying oxidative stress–derived lipid adducts (isolevuglandins) as neoantigens that activate T cells via dendritic cells in hypertension and lupus. His lab identified specific kidney-derived antigenic peptides and demonstrated sex differences in renal T-cell activation. He also described HLA-dependent variability in antigen presentation that may predict human risk.<br /><br />Dr. David Mattson discussed salt-sensitive hypertension (Dahl SS rats), showing high salt drives renal immune-cell infiltration, kidney damage, and progressive hypertension. CD4 T cells, NOX2-derived ROS signaling, and TH17/IL-17 pathways amplify disease; reducing pressure or blocking IL-17 signaling attenuated injury and hypertension.

Asset Subtitle

Moderator(s): Jennifer Pollock, Justin Van Beusecum

Presentation(s):

Regulation of Sodium Transport by Cytokines in Kidney Diseases - Steven Crowley
Mechanisms of Autoimmune Kidney Damage in Hypertension - Keisa Mathis
Inflammation and Hypertensive Kidney Disease - David Harrison
Salt, Immunity, and Hypertension - David Mattson

Meta Tag

Date 11/7/2025

Pathway 1 Hypertension and Cardiorenal Disorders

Session ID 507282

Keywords

inflammation-driven hypertension

chronic kidney disease (CKD) hypertension

renal sodium handling

cytokines IL-1β IL-6 TNF

IL-17/TH17 pathway

IFN-γ signaling

renal sodium transporters (NHE3 NCC ENaC NKCC2)

thick ascending limb nitric oxide suppression

dendritic cell–T cell activation

A20 (TNFAIP3) anti-inflammatory regulator

kidney-targeted gene therapy (AAV)

systemic lupus erythematosus (SLE) hypertension

cholinergic anti-inflammatory pathway

galantamine neuromodulation

isolevuglandins (IsoLG) neoantigens oxidative stress