Advancements in understanding the mechanisms of lung–kidney crosstalk

This narrative review delves into the intricate interplay between the lungs and the kidneys, with a focus on elucidating the pathogenesis of diseases influenced by immunological factors, acid–base regulation, and blood gas disturbances, as well as assessing the effects of various therapeutic modalities on these interactions. Key disorders, such as anti-glomerular basement membrane (anti-GBM) disease, the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and Anti-neutrophil Cytoplasmic Antibodies (ANCA) associated vasculitis (AAV), are also examined to shed light on their underlying mechanisms. This review also explores the relationship between acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), emphasizing how inflammatory mediators can lead to systemic damage and impact multiple organs. In ARDS, fluid overload exacerbates pulmonary edema, while imbalances in blood volume, such as hypovolemia or hypervolemia, can precipitate renal dysfunction. The review highlights how mechanical ventilation strategies can compromise renal blood flow, trigger systemic inflammation, and induce hemodynamic and neurohormonal alterations, all contributing to lung and kidney damage. The impact of extracorporeal membrane oxygenation (ECMO) on lung–kidney interactions is evaluated, highlighting its role in severe respiratory failure and its renal implications. Emerging therapies, such as mesenchymal stem cells and extracellular vesicles, are discussed as promising avenues to mitigate organ damage and enhance outcomes in critically ill patients. Overall, this review offers a nuanced exploration of lung–kidney dynamics, bridging historical insights with contemporary perspectives. It underscores the clinical significance of these interactions in critically ill patients and advocates for integrated management approaches to optimize patient outcomes.

Key Points

1. Lung-Kidney Crosstalk Mechanisms: Includes acid–base regulation, fluid balance, and immunological responses, with disruptions leading to systemic organ damage.
2. Classic Interactions: Conditions like anti-GBM disease, SIADH, and AAV exemplify immune-mediated damage affecting both organs, driven by cytokine storms and inflammatory cascades.
3. Acid-Base and Blood Gas Dynamics: Lungs manage CO₂ elimination, while kidneys regulate bicarbonate and hydrogen ion excretion. Imbalances due to ARDS or AKI exacerbate systemic acidosis or alkalosis.
4. ARDS and AKI Interplay: Fluid overload, hypoxemia, and systemic inflammation during ARDS precipitate AKI, while AKI-induced inflammatory mediators exacerbate lung injury.
5. Impact of Mechanical Ventilation: High PEEP and invasive ventilation contribute to renal perfusion impairment via hemodynamic changes and systemic inflammation.
6. Role of ECMO: While veno-venous ECMO (VV-ECMO) alleviates hypoxemia and protects kidneys, veno-arterial ECMO (VA-ECMO) increases the risk of AKI due to non-pulsatile flow and hypercoagulability.
7. Emerging Therapies: Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) offer promising anti-inflammatory and regenerative properties for mitigating organ crosstalk damage.
8. Biomarker-Guided Interventions: Markers like NGAL and IL-6 help identify early crosstalk dysregulation, enabling timely interventions.
9. Therapeutic Challenges: Integrated ECMO and CRRT systems face complications like embolism and hemolysis but can support severe cases of ARDS and AKI.
10. Future Directions: Emphasizes research on MSCs, EVs, and biomarker utilization to refine diagnostics and develop targeted interventions for lung-kidney syndromes.

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