Increased phosphorylated yes-associated protein expression in podocytopathies supports Hippo pathway role in podocyte damage

Objectives: Recent studies highlight the role of Hippo signaling pathway molecules, particularly yes-associated protein (YAP) and kidney and brain expressed protein (KIBRA), in regulating podocyte homeostasis. The main objective of the study is to study the immunohistochemical expression of phosphorylated YAP (p-YAP) and KIBRA in podocytopathies and to correlate it with different clinico-pathological factors. Materials and Methods: The study included all histologically proven cases of focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) from January 2022 to September 2024. Clinical and pathological parameters were recorded. All cases were subjected to immunohistochemical staining for p-YAP. KIBRA immunostaining was performed in a subset of cases. Statistical analysis: Data were summarized using Microsoft Excel 2020. Comparisons between groups were made using the Mann-Whitney U Test. Pearson Chi-Square test was used to compare categorical variables. Results: The study included 66 cases of FSGS and six cases of MCD. p-YAP immunohistochemistry was interpreted in 68 cases: 62 FSGS cases and six MCD cases. Among the FSGS cases, 42 cases had positive staining for p-YAP. No association of p-YAP staining was observed with different clinical and pathological features. KIBRA expression was observed in six of the eight cases tested. Conclusions: The presence of p-YAP staining in a significant proportion of FSGS cases raises a possible role of the Hippo signaling pathway, which was further strengthened by demonstration of KIBRA staining in a subset of such cases. Future studies should be planned to study a large cohort of proteinuric patients and explore the potential implications of the Hippo signaling pathway in such cases.