Elevated Exposure to Air Pollutants Accelerates Primary Glomerular Disease Progression

Environmental contributors to kidney disease progression remain elusive. We explored how residential air pollution affects disease progression in patients with primary glomerulopathies.

Nephrotic Syndrome Study Network (NEPTUNE) and CureGlomerulonephropathy (CureGN) participants with residential census tract data and ≥2 years of follow-up were included. Using Cox proportional hazards models, the associations per doubling in annual average baseline concentrations of total particulate matter with diameter ≤2.5 μm (PM_2.5) and its components, black carbon (BC), and sulfate, with time to ≥40% decline in estimated glomerular filtration rate (eGFR) or kidney failure were estimated. Serum tumour necrosis factor levels and kidney tissue transcriptomic inflammatory pathway activation scores were used as molecular markers of disease progression.

PM_2.5, BC, and sulfate exposures were comparable in NEPTUNE (n = 228) and CureGN (n = 697). In both cohorts, participants from areas with higher levels of pollutants had lower eGFR, were older and more likely self-reported racial and ethnic minorities. In a fully adjusted model combining both cohorts, kidney disease progression was associated with PM_2.5 (adjusted hazard ratio 1.55 [95% confidence interval: 1.00-2.38], P = 0.0489) and BC (adjusted hazard ratio 1.43 [95% confidence interval: 0.98-2.07], P = 0.0608) exposure. Sulfate and PM_2.5 exposure were positively correlated with serum tumour necrosis factor (TNF) (P = 0.003) and interleukin-1β levels (P = 0.03), respectively. Sulfate exposure was also directly associated with transcriptional activation of the TNF and JAK-STAT signaling pathways in kidneys (r = 0.55-0.67, P-value <0.01).

Elevated exposure to select air pollutants is associated with increased risk of disease progression and systemic inflammation in patients with primary.