# Uremic Toxins and the Lung Alveolar Capillary Barrier: A Narrative Review

## TL;DR

This review explores how uremic toxins from chronic kidney disease harm lung function by damaging the alveolar capillary barrier and causing inflammation and oxidative stress.

## Contribution

The paper provides a comprehensive narrative review on the mechanisms by which uremic toxins affect lung tissue in chronic kidney disease.

## Key findings

- Uremic toxins disrupt the alveolar-capillary barrier through oxidative stress and inflammation.
- Shared signaling pathways like MAPK, AhR, RAGE, and NF-κB are involved in uremic toxin-induced lung damage.
- The harmful interactions between CKD and lung disease are not fully understood, with more evidence for acute kidney injury.

## Abstract

Introduction: Uremic toxins have been shown to cause adverse pulmonary effects by inducing endothelial and epithelial dysfunction, disrupting the alveolar-capillary barrier, and increasing inflammation and oxidative stress. This article reviews these effects with a specific focus on chronic kidney disease and the mechanisms by which uremic toxins affect lung tissue. Methods: A narrative review was conducted using keywords related to uremic toxins and lung injury to search the PubMed database. An advanced literature review was conducted in PubMed to identify studies explaining the mechanisms underlying lung pathophysiology in chronic kidney disease (CKD), with particular focus on CKD-induced pulmonary epithelial and endothelial dysfunction. Additionally, to highlight the pathological processes of lung congestion in CKD, studies on CKD-induced dysfunction of the alveolar-capillary barrier were retrieved. Studies published up to November 2025 were evaluated. Results: A total of 148 articles were reviewed in full text. Uremic toxins negatively impact lung tissue structure and function through multiple mechanisms, including oxidative stress, inflammation, and direct effects. Uremic toxins appear to share signaling pathways in endothelial cells, including those linked to Mitogen-activated protein kinases (MAPK), the Aryl Hydrocarbon Receptor (AhR), the receptor for advanced glycation end products (RAGE), and pro-inflammatory transcription factors such as nuclear factor κB (NF-κB). Additionally, oxidative stress acts as a pro-inflammatory signal shared by several uremic toxins. The mechanisms behind the harmful interactions between CKD and lung disease are mostly unknown, although more evidence exists for acute kidney injury (AKI). Conclusions: Chronic kidney disease, which leads to the buildup of uremic toxins, negatively affects the lungs. Overall, the accumulation of uremic toxins in CKD impairs endothelial and epithelial cells and the alveolar capillary barrier. Further research is needed to understand the specific mechanisms underlying these effects and to identify therapeutic options to protect the lungs in these patients.