Cumulative smoking dose is associated with subclinical renal injury: a pathological study in individuals without chronic kidney disease

ABSTRACT Background Epidemiological studies have identified smoking as an independent risk factor for development of chronic kidney disease. However, the early renal pathological lesions have not been clearly elucidated. Methods We investigated time-zero biopsy specimens from 547 living kidney donors and evaluated the relationships between smoking and renal histological changes, including arteriolar hyalinization, intimal thickening of small–medium arteries, global glomerulosclerosis, and interstitial fibrosis and tubular atrophy (IF/TA). Results A total of 199 subjects (36.4%) had smoking history; 92 (16.8%) and 107 (19.6%) subjects had <20 pack-years and ≥20 pack-years of smoking, respectively. Cumulative smoking dose was significantly associated with prevalence of arteriolar hyalinization: the multivariable-adjusted odds ratio (OR) per 20 pack-year increase was 1.50 (95% confidence interval 1.15–1.97). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.76 (1.01–3.09) and 2.56 (1.48–4.44), respectively. Smoking was also associated with prevalence of >10% global glomerulosclerosis: the OR per 20 pack-year increase was 1.24 (0.96–1.59). The ORs for smokers with <20 pack-years and ≥20 pack-years versus never-smokers were 1.50 (0.98–2.78) and 2.11 (1.18–3.79), respectively. The ORs for these pathological changes increased significantly depending on cumulative smoking dose. Intimal thickening of small–medium arteries and IF/TA were not associated with smoking status. The prevalence of arteriolar hyalinization remained higher in patients with ≥10 years since smoking cessation than in never-smokers [OR 2.23 (1.03–4.83)]. Conclusions Subclinical pathological injury caused by smoking is potentially associated with renal arteriolar hyalinization and glomerular ischaemia.