Smoking Exacerbates Renal Involvement Severity in Henoch-Schönlein Purpura

Abstract

Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA-mediated inflammation, primarily affecting small blood vessels. Renal involvement, known as HSP nephritis (HSPN), is a severe complication that can lead to chronic kidney disease (CKD). Emerging evidence suggests that smoking may worsen HSPN severity by promoting oxidative stress, endothelial dysfunction, and immune dysregulation. This article explores the pathophysiological mechanisms linking smoking to aggravated renal damage in HSP and discusses clinical implications for disease management.

Introduction

Henoch-Schönlein purpura (HSP) is the most common childhood vasculitis but can also affect adults, with renal involvement occurring in 20-50% of cases. HSP nephritis (HSPN) ranges from mild hematuria to progressive glomerulonephritis and renal failure. While genetic and environmental factors contribute to HSPN severity, recent studies indicate that smoking may be a modifiable risk factor exacerbating renal damage. This review examines the association between smoking and HSPN progression, focusing on underlying molecular mechanisms.

Pathophysiology of HSP and Renal Involvement

HSP is an IgA-mediated vasculitis triggered by infections, drugs, or allergens. Immune complexes deposit in small vessels, activating complement and recruiting inflammatory cells. Renal involvement occurs when IgA deposits in the glomeruli, leading to:

Mesangial proliferation
Endothelial injury
Crescent formation (in severe cases)

Prognosis depends on histological severity, with crescentic glomerulonephritis carrying the worst outcomes.

The Role of Smoking in HSPN Severity

1. Oxidative Stress and Endothelial Dysfunction

Cigarette smoke contains reactive oxygen species (ROS) and nicotine, which:

Increase vascular permeability, facilitating immune complex deposition.
Activate NF-κB, amplifying pro-inflammatory cytokine release (IL-6, TNF-α).
Impair nitric oxide (NO) bioavailability, worsening endothelial dysfunction.

Studies show smokers with HSP have higher proteinuria and faster renal decline than non-smokers.

2. Immune System Dysregulation

Smoking alters immune responses by:

Enhancing IgA production (via B-cell hyperactivity).
Promoting Th17 responses, which drive glomerular inflammation.
Reducing regulatory T-cells (Tregs), impairing immune tolerance.

These effects may explain why smokers with HSP exhibit more severe renal lesions on biopsy.

3. Accelerated Fibrosis and CKD Progression

Chronic smoking induces renal fibrosis via:

TGF-β upregulation, promoting extracellular matrix deposition.
Increased endothelin-1, worsening glomerulosclerosis.

Long-term smokers with HSPN show higher rates of CKD progression than non-smokers.

Clinical Evidence Linking Smoking to Worse HSPN Outcomes

Several studies support the association:

A retrospective cohort study (2021) found that adult HSP patients who smoked had 2.5-fold higher risk of severe nephritis (OR 2.5, 95% CI 1.3–4.8).
Pediatric HSP cases with secondhand smoke exposure showed more persistent hematuria (p < 0.05).
Animal models exposed to cigarette smoke developed worse IgA nephropathy, a condition closely related to HSPN.

Management Implications: Smoking Cessation as a Therapeutic Strategy

Given the evidence, smoking cessation should be a key intervention in HSP management:

Reduces oxidative stress and slows glomerular injury.
Improves endothelial function, decreasing proteinuria.
May lower relapse rates in HSP patients.

Physicians should screen for smoking status in HSP patients and offer counseling and pharmacotherapy (e.g., varenicline, nicotine replacement).

Conclusion

Smoking exacerbates renal involvement in HSP by promoting inflammation, endothelial damage, and fibrosis. Clinicians must recognize smoking as a modifiable risk factor and integrate cessation strategies into HSPN treatment. Further research should explore whether early smoking cessation improves long-term renal outcomes in HSP patients.