Henoch-Schönlein Purpura Nephritis: Understanding Disease Grading and Pediatric Classification

Henoch-Schönlein purpura nephritis (HSPN) is a form of secondary glomerulonephritis that arises as a complication of Henoch-Schönlein purpura, an immune-mediated small vessel vasculitis. While this condition can affect both children and adults, the approach to diagnosis and classification differs significantly between age groups—particularly when it comes to disease grading.

Differences in HSPN Grading Between Adults and Children

Unlike many other kidney diseases, HSPN is not formally graded in adult patients. Clinicians typically assess severity based on clinical symptoms, laboratory findings, and biopsy results without assigning a standardized pathological grade. This lack of formal classification stems from the variable presentation and relatively lower incidence of severe renal involvement in adults compared to pediatric cases.

In contrast, children with HSPN are systematically classified according to histopathological features observed during renal biopsy. The standard framework used worldwide is established by the International Study of Kidney Disease in Children (ISKDC), which divides the disease into six distinct classes based on the extent of glomerular damage and inflammatory changes.

Pediatric Histological Classification of HSPN

Class I – Minimal Change Disease

This is the mildest form of HSPN, where kidney tissue appears almost normal under light microscopy. There may be minor immunoglobulin A (IgA) deposits visible through immunofluorescence, but no significant structural changes or cellular proliferation are detected. Patients in this category usually have an excellent prognosis with minimal intervention.

Class II – Isolated Mesangial Proliferation

In Class II, there is evidence of increased cellularity limited to the mesangial areas of the glomeruli. No crescents or segmental lesions are present. This stage often correlates with mild proteinuria or microscopic hematuria and generally responds well to conservative management.

Class III – Mesangial Proliferation with Crescents or Segmental Lesions (≤50%)

At this stage, more than half of the glomeruli remain unaffected, but up to 50% show either crescent formation or segmental necrosis. This intermediate level of injury indicates a higher risk for progressive renal dysfunction and may require immunosuppressive therapy depending on clinical severity.

Class IV – Diffuse Mesangial Proliferation with Crescents (50–75%)

Class IV represents a more severe manifestation, involving between 50% and 75% of glomeruli with crescents or segmental damage. These patients often present with nephrotic-range proteinuria, hypertension, and impaired kidney function. Aggressive treatment with corticosteroids and additional immunomodulatory agents like cyclophosphamide or mycophenolate mofetil is commonly recommended.

Class V – Severe Glomerular Involvement (>75%)

When over three-quarters of glomeruli exhibit crescentic or segmental changes, the condition is classified as Class V. This level of injury carries a substantial risk of chronic kidney disease or end-stage renal failure if not promptly managed. Multidrug regimens and close monitoring are essential for preserving long-term renal function.

Class VI – Membranoproliferative-Like Pattern

The rarest and most structurally complex form, Class VI mimics membranoproliferative glomerulonephritis (MPGN). It features global double contour formation of the glomerular basement membrane due to immune complex deposition. This pattern suggests prolonged immune system activation and often requires advanced diagnostic evaluation and intensive treatment strategies.

Clinical Implications and Prognosis

The ISKDC classification plays a crucial role in guiding treatment decisions and predicting outcomes. Higher histological grades correlate strongly with poorer renal prognosis, especially in children presenting with nephrotic syndrome, acute kidney injury, or extensive crescent formation. Early biopsy and accurate grading enable timely therapeutic interventions that can significantly improve long-term health outcomes.

Moreover, integrating pathological findings with clinical data—such as blood pressure levels, serum creatinine, urine protein-to-creatinine ratio, and response to initial therapy—allows for a comprehensive assessment tailored to each patient's unique needs.

Conclusion

While Henoch-Schönlein purpura nephritis remains ungraded in adults, the six-tier pediatric classification system offers valuable insights into disease severity and helps shape individualized care plans. Understanding these categories empowers healthcare providers and families alike to make informed decisions about monitoring, treatment, and follow-up, ultimately enhancing quality of life and reducing the burden of chronic kidney disease. Ongoing research continues to refine diagnostic criteria and explore targeted therapies to further improve prognosis across all classes.