D21-01 Kidney Tubular Epithelial Responses to Whole-Lung Allergen-Induced Asthma Exacerbation

Introduction Asthma is characterized by airway inflammation driven by epithelial mechanisms that initiate and sustain disease. Airway epithelial cells regulate surface liquid pH, supporting mucociliary function and antimicrobial defense by exporting protons (H+) through H+-ATPase transporters. In asthma, epithelial proton transport is impaired, disrupting pH regulation. Functionally analogous H+-ATPase transporters in kidney tubules maintain acid-base and electrolyte homeostasis; their dysfunction causes renal tubular acidosis (RTA) and kidney stones. We hypothesized that epithelial dysregulation in asthma may be systemic and present in kidney tubular epithelium. To test this, we assessed glomerular filtration rate (GFR), urinary crystals, and electrolytes in healthy controls and asthmatics following whole-lung allergen challenge (WLAC). Methods Medical diagnoses, blood, and 24-hour urine collections were obtained in healthy controls (n = 48), non-severe asthmatics (n = 27), severe asthmatics (n = 24), and asthmatics (N = 11) who underwent WLAC. Results 41.2% of asthmatics reported kidney disease as opposed to 18.75% of healthy controls (P = 0.02). Urinary crystals were present in 41.2% of asthmatic, as opposed to 14.5% of controls (P = 0.0001). GFR was lower in severe asthmatics as compared to controls and non-severe asthmatics (severe asthma, mean [standard error]: 81.6 mL/min 1.732 [0.9], non-severe asthma, 83.7 mL/min 1.732 [0.8], controls, 86.3 mL/min 1.732 [0.6]; P = 0.003). Serum electrolytes were similar among the population. Except for higher urinary citrate in asthmatics (healthy control: 0.35 [0.030], asthmatic: 0.44 [0.03], p = 0.017], urine electrolytes were similar. WLAC decreased serum potassium in asthmatics (K baseline: 4.21 mmol/L [0.09 mmol/L] to 3.86 mmol/L [0.11 mmol/L], P = 0.039), urinary potassium (K baseline: 0.64 nmol/mg Cr [0.11] to 0.31 nmol/mg Cr [0.039], P = 0.008), and fractional excretion of potassium (FE-K baseline: 0.11 [0.02] to 0.06 [0.01], P = 0.01). While serum phosphorus was similar before and after WLAC (P = 0.25), urine phosphorus (Phos) increased (Phos baseline: 0.36 mg/mg Cr [0.05] to 0.59 mg/mg Cr [0.08], P = 0.01), and fractional excretion of Phos increased after WLAC (FE-Phos : 0.085 [0.007] to 0.12 [0.01], P = 0.006). Six individuals in the WLAC cohort had urinary crystals present. Discussion GFR is reduced in asthma, with higher rates of urinary crystals and kidney stones. WLAC-induced inflammation alters renal potassium and phosphorus excretion, indicating tubular epithelial involvement. Conclusion Inflammation in asthma is associated with renal tubular epithelial alterations that disrupt electrolyte handling and increase nephrolithiasis susceptibility, suggesting epithelial dysregulation in asthma extends beyond the airways.