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

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.