Work

Digital pathology approach for the classification of focal and segmental glomerulosclerosis

Year: 2026

Type: article

Abstract: Background : Focal and segmental glomerulosclerosis (FSGS) refers to various diseases with different pathophysiological mechanisms and treatments. Primary FSGS (pFSGS) is dependent on immunological factors and is treated with immunosuppressants. However, the histological lesions by light microscopy are not specific and do not reflect a precise etiology. The aim of this study is to categorize FSGS biopsies into etiological groups using digital pathology combined with clinical parameters. Methods It was a Retrospective observational multicentric study . Three University hospitals in Paris and Bordeaux . 58 patients with pFSGS and maladaptative FSGS (mFSGS) on kidney biopsies in a selected “Ultraphenotyped cohort”. Secondly, a “clinical cohort” of 89 patients with non-selected FSGS. Mean Interglomerular Area (MIA) Firstly we evaluated the ability of histological morphometric parameters to discriminate pFSGS and maladaptive FSGS (mFSGS) on kidney biopsies in a ultraphenotyped cohort of normative pFSGS and mFSGS patients (n=58), and performed a multivariate analysis to identify variables associated with the type of FSGS, leading to the identification of the Mean Interglomerular Area (MIA) as a marker to distinguish pFSGS from mFSGS. Secondly, we evaluated the discriminative value of this parameter in a clinical cohort(n=89) including primary, maladaptive and undetermined FSGS Results High MIA classified mFSGS vs pFSGS in the ultraphenotyped cohort, even after stratification by age, eGFR and proteinuria. In the clinical cohort MIA was also significantly lower in primitive FSGS. Although MIA strongly correlated with serum albumin (Figure 5), a classical marker of pFSGS, they conflicted in 30% of patients. In this subset relying solely on serum albumin frequently misclassified patients by FSGS subtype (27%), highlighting the usefulness of combining MIA with serum albumin to adjudicate FSGS subtypes. FSGS of uncertain origin segregated with either pFSGS or mFSGS cases on a MIA by albumin graph, suggesting that they do not constitute a different pathological entity. Conclusion Digital pathology, in conjunction with simple biological features, is a useful tool for FSGS classification, suggesting that it might improve the design of future therapeutic and mechanistic FSGS studies.

Source: Scientific Reports

DOI: 10.1038/s41598-026-77202-4