Particulate matter exposure and end-stage renal disease risk in IgA nephropathy

Long-term exposure to fine particulate matter (PM₂.₅) and coarse particles (PM₁₀) significantly accelerates progression to end-stage renal disease (ESRD) among patients with biopsy-proven IgA nephropathy (IgAN), with risk tripling beyond concentration thresholds of 50 μg/m³ for PM₂.₅ and 77 μg/m³ for PM₁₀, independent of classical clinical predictors. A retrospective cohort of 1,768 IgAN patients followed from 2010 to 2021 in Sichuan Province recorded 209 ESRD events. Satellite-derived 1-km-resolution pollutant concentrations were linked to residential addresses; cumulative post-baseline mean PM₂.₅ ranged 9–87 μg/m³ (median 46 μg/m³) and PM₁₀ 19–145 μg/m³ (median 74 μg/m³). Fully-adjusted Cox models showed highest-quartile PM₂.₅ exposure carried a hazard ratio of 3.49 (95% CI 2.16–5.62) and PM₁₀ 3.75 (2.33–6.06) versus the lowest quartile; each 10 μg/m³ increment raised ESRD risk by 62% and 36%, respectively. Restricted cubic splines revealed sharply upward inflections above the identified thresholds, indicating nonlinear dose–response.

Group-based trajectory modelling of five-year pre-baseline exposure identified three distinct patterns: consistently high-fluctuating PM₂.₅ (mean 77 μg/m³, 53% of cohort) conferred 78% greater ESRD risk compared with a light-to-moderate decreasing trajectory (mean 43 μg/m³), whereas PM₁₀ trajectories showed no significant gradient. Stratified analyses demonstrated stronger associations among patients with baseline eGFR ≥ 60 mL/min/1.73 m² or proteinuria < 2 g/day, implying pollution acts early in the disease course. Sensitivity analyses—lag windows, exclusion of early ESRD cases, and quantile-g-computation mixture modelling—confirmed robustness; joint exposure to both pollutants increased risk by 75% per weighted quartile increment.

Biologic plausibility rests on particulate-induced systemic oxidative stress, endothelial dysfunction, and mucosal immune modulation that amplifies IgAN-specific pathways: up-regulation of TLRs, IL-17A and Th17 skewing may boost galactose-deficient IgA1 production, while glomerular deposition of particles or inflammatory mediators accelerates mesangial injury and fibrosis. The study’s strengths include pathological confirmation, high-resolution exposure data, and dual time-window assessment; limitations are single-centre design, lack of gaseous pollutants, and fixed covariate models. Overall, findings establish ambient particulate matter as a modifiable risk factor for IgAN progression, supporting early pollution mitigation and reinforcing global clean-air policies to curb renal as well as cardiopulmonary morbidity.