Inhaled Halogen‐Induced Oxidative Renal Damage and Dysfunction: A Lung Heart Kidney Axis

TL;DR

This study shows that inhaling halogen gases can cause lung and heart damage, which leads to kidney injury and dysfunction through oxidative stress and reduced blood flow.

Contribution

The study identifies a lung-heart-kidney axis linking halogen exposure to oxidative stress-induced renal damage and dysfunction.

Findings

Halogen exposure increases blood creatinine and urea nitrogen, indicating acute kidney stress.

Urinary biomarkers like KIM-1 and NGAL show significant kidney injury and structural damage.

Oxidative stress markers and fibrosis in renal tissues suggest progression from AKI to CKD.

Abstract

Acute exposure to halogen gases causes extensive injury to the lungs and heart that may be fatal. To evaluate secondary renal complications subsequent to pulmonary and cardiac dysfunction, rats were exposed to bromine and chlorine, and their renal function and injury biomarkers were assessed post exposure. Bromine or chlorine caused a significant increase in arterial blood creatinine and urea nitrogen (BUN) suggesting acute renal stress. Rats exposed to either of these halogens also exhibited increased total protein, albumin, and retinol binding protein 4 (RBP4) in the urine indicating significant kidney damage. Significant increases in kidney injury markers such as kidney injury molecule‐1 (KIM‐1), neutrophil gelatinase‐associated lipocalin (NGAL), and osteopontin were observed in the urine and kidney tissues in addition to structural changes further demonstrating tubular damage and cast formation. Hemodynamic parameters such as the mean arterial blood pressure (MAP) and renal vascular resistance (RVR) increased, while the renal artery diameter and renal blood flow decreased significantly. Observation after 4 weeks, following bromine exposure, demonstrated increased collagen volume in the interstitium and the glomerulus, and increased fibrosis characteristic of the progression of acute kidney injury (AKI) to chronic kidney disease (CKD). The renal tissues showed increased myeloperoxidase and plasma oxidized low‐density lipoproteins further indicating oxidative stress in the halogen exposed animals. Kidneys are highly susceptible to oxidative stress which causes cell damage, death, and renal dysfunction leading to AKI. Clinically, these data suggest that victims of halogen exposure are at increased risk of cardiovascular events as well as renal dysfunction and AKI.

Mechanisms of lung‐heart‐kidney interaction in inducing organ injury after chemical inhalation. Acute exposure to halogen gases causes extensive lung injury and acute cardiac damage leading to fatalities. Formation of highly reactive halogenated molecules in the pulmonary bed and their circulation resulting in oxidative stress and inflammation was responsible for the toxicity. Kidneys are highly susceptible to oxidative stress, which causes oxidative cell damage, cell death, and renal dysfunction leading to acute kidney injury. This damage was enhanced by reduced perfusion due to the parallel cardiac damage and dysfunction. A vicious cycle of secondary organ interaction perpetuates the injury and enhances the toxicity (Related but previously published work is depicted in the gray squares).

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