The Impact of Tobacco Smoke Exposure on Glomerulonephritis

Background Glomerulonephritis (GN) represents a major cause of chronic kidney disease globally, with environmental factors increasingly recognised as disease contributors. While tobacco exposure has been implicated in kidney disease, its specific role in glomerulonephritis pathogenesis and progression remains incompletely understood. Understanding tobacco-GN relationships extends beyond individual patient care to public health implications, as establishing clear associations with GN development and progression could inform targeted prevention strategies.

Methods Systematically reviewed studies examining tobacco exposure and glomerulonephritis across both adult and paediatric populations. Analysed pathophysiological mechanisms linking tobacco to glomerular damage and reviewed clinical evidence across multiple GN subtypes, including IgA nephropathy, ANCA (anti-Neutrophil Cytoplasmic Antibodies)-associated vasculitis, anti-GBM (glomerular basement membrane) disease, and lupus nephritis.

Results Multiple biological pathways link tobacco exposure to glomerular damage. Tobacco exposure induces hemodynamic changes including increased renal vascular resistance, decreased glomerular filtration rate, and elevated intraglomerular pressure. Smoking causes endothelial dysfunction, depleting nitric oxide availability and promoting renal artery atherosclerosis. Cigarette smoke induces oxidative stress leading to glutathione depletion and cellular damage. Nicotine directly affects podocytes, reducing expression of maturity markers and compromising glomerular filtration barrier integrity. Clinical studies consistently demonstrate worse outcomes in smokers across GN subtypes. In IgA nephropathy, smoking accelerates progression to end-stage renal disease, particularly in men with significant smoking histories. For ANCA-associated vasculitis, smoking represents a significant risk factor for development and progression. Anti-GBM disease shows the most dramatic association, with virtually all smokers developing pulmonary haemorrhage compared to only 20% of non-smokers. In lupus nephritis, smoking reduces median time to end-stage renal disease from over 273 months to 145 months. The NEPTUNE cohort study revealed that passive smoking in children increases odds of nephrotic-range proteinuria by 2.64-fold.

Conclusion The findings across different study designs and populations support the clinical significance of these relationships. The evidence is sufficient to warrant routine tobacco exposure assessment, including both active and passive exposure, and smoking cessation counselling as standard components of glomerulonephritis management. From a public health perspective, tobacco control measures may represent an important strategy for reducing the global burden of glomerular disease. For practicing nephrologists, smoking cessation should be treated as a kidney-protective intervention comparable to blood pressure control and proteinuria reduction, with patients receiving intensive cessation support as part of comprehensive kidney care.