**7. Controversial aspects of ISN/RPS classification and NIH activity and chronicity indices**

The classification of INS/RPS was proposed to standardize and emphasize the most relevant lesions to guide the treatment of LN. Recently, several retrospective validation studies concerning the utility of the classification were performed. These studies have highlighted the limitations of the classification and of the activity and chronicity indices. In these reports, the main weaknesses of the classification include: 1. Tubulointerstitial and vascular lesions not included in the system; 2. No correlation between the lesions with long-term outcome; 3. Poor interobserver reproducibility of both active and chronic lesions [12, 13, 32–35].

Tubulointerstitial and vascular lesions correlated closely with clinical disease activity and renal outcome in many studies [14, 19–21]. It is necessary at least to mention these lesions in the diagnosis of the biopsy report.

The classification of LN, especially classes IV-G and IV-S, and the activity and chronicity indexes have not shown a satisfactory correlation with the long-term outcome of the disease [1, 7, 8, 13]. After treatment induction and even during the maintenance phase, the inflammatory process may persist and go unnoticed clinically. Some authors recommend repeating the renal biopsy after treatment to better assess the response to treatment and predict the course of the disease [1, 7, 8, 29]. There is also a poor reproducibility among pathologists to apply these criteria that limits their application in practice [1, 36, 37]. It is a consensus that the classification of LN as well as the criteria of activity and chronicity of the disease should be reviewed [1, 7, 8, 36, 37].
