The classification of patients with FSGS lesions is often challenging due to the broad spectrum of underlying causes, our limited understanding of the pathophysiology, and the poor correlation between histopathology and treatment response and clinical outcomes. Therefore, many experts suggest a clinicopathological approach rather than a morphological approach to FSGS classification (morphometrics school of thought vs. pathomechanism-based school of view). The classification into pathomechanism-based (e.g., underlying pathophysiology) categories have been proposed by Dr. Helmut Rennke, Dr. Jeffrey Kopp, and others and discussed in detail during one of the most widely watched GlomCon seminar (https://youtu.be/2kN5MpTOcG8) and most commonly referenced articles on this topic (https://doi.org/10.2215/CJN.05960616).
As reviewed by De Vriese et al. (https://doi.org/10.1681/ASN.2017090958), a classification based on clinicopathological assessment will improve clinical management and further guide the design and implementation of clinical trials. The importance of a clinicopathologic classification is based on the different clinical presentations, management, and prognostic implications of the various disorders, all presenting as “FSGS” on histopathology. A clinical practice solely based on histopathological injury patterns is insufficient to predict treatment response, and patients could undergo needless immunosuppression. The KDIGO 2021 guidelines adopted this proposed pathomechanism-based approach to FSGS classification, differentiating between primary (immune medicated), genetic, secondary, and undetermined causes (https://doi.org/10.1016/j.kint.2021.05.021). Figure 1 summarizes this classification.