Henoch-Schönlein Purpura Nephritis: Understanding Tubulointerstitial Grading for Improved Prognosis and Treatment

Henoch-Schönlein purpura nephritis (HSPN) presents a complex clinical picture with significant variability in symptoms and pathological findings among patients. Due to the diverse nature of renal involvement, establishing a standardized approach for kidney biopsy indications remains challenging. To enhance the accuracy of assessing kidney damage, predicting disease outcomes, and evaluating treatment effectiveness, integrating tubulointerstitial histopathological grading into the existing classification system offers a more comprehensive framework.

The Importance of Tubulointerstitial Assessment in HSPN

While glomerular injury has traditionally been the focus in HSPN evaluation, emerging evidence highlights the critical role of tubulointerstitial changes in determining long-term renal prognosis. Damage to the renal tubules and surrounding interstitial tissue often correlates more closely with declining kidney function than glomerular lesions alone. Therefore, incorporating tubulointerstitial grading provides clinicians with deeper insights into disease progression and helps guide therapeutic decisions.

A Four-Tiered Grading System for Tubulointerstitial Injury

To standardize assessment and improve communication among healthcare providers, a four-level grading system based on histological features of the tubules and interstitium has been proposed. This system enables more precise stratification of disease severity and supports personalized patient management.

Grade 1: Mild Tubular Changes

This initial stage is characterized by mild structural alterations in the renal tubules, including slight tubular dilation and minimal epithelial cell degeneration. There is no significant interstitial inflammation or fibrosis at this level. Patients in Grade 1 typically exhibit stable renal function and respond well to conservative treatment approaches.

Grade 2: Early Interstitial Fibrosis and Inflammation

In Grade 2, histological examination reveals the onset of interstitial fibrosis accompanied by tubular atrophy affecting less than 20% of tubules. Scattered inflammatory cell infiltration—often composed of lymphocytes and monocytes—is observed within the interstitium. This stage indicates progressive kidney injury and may require closer monitoring and early immunosuppressive intervention to prevent further deterioration.

Grade 3: Moderate to Severe Tubular Atrophy with Widespread Inflammation

At this intermediate-to-advanced stage, tubular atrophy involves 20% to 50% of the cortical tubules. Interstitial fibrosis becomes more pronounced, and inflammatory infiltrates may appear either focally or diffusely distributed. The presence of ongoing inflammation suggests active disease, making this grade a crucial window for aggressive therapy to halt irreversible damage.

Grade 4: Extensive Tubulointerstitial Destruction

Grade 4 represents the most severe form of tubulointerstitial injury, with over 50% of renal tubules showing atrophy and advanced interstitial fibrosis. Inflammatory cells may be present in both focal and diffuse patterns, indicating persistent immune activity. This stage is strongly associated with impaired kidney function and a higher risk of progressing to chronic kidney disease (CKD) or end-stage renal disease (ESRD), necessitating intensive treatment and long-term follow-up.

Clinical Implications and Future Directions

Integrating tubulointerstitial grading into routine kidney biopsy reports can significantly improve prognostic accuracy in HSPN patients. It allows for earlier identification of high-risk individuals who may benefit from prompt, targeted therapies. Furthermore, this classification supports clinical research by enabling better patient stratification in trials evaluating new treatments.

As precision medicine continues to evolve, combining histopathological grading with biomarkers and genetic profiling could pave the way for even more individualized care. For now, adopting a structured tubulointerstitial grading system represents a practical and impactful step toward optimizing the management of Henoch-Schönlein purpura nephritis worldwide.