Development of a clinical nomogram for predicting hemorrhagic rupture in renal angiomyolipoma and analysis of molecular correlates (CD34, PPARG, and PTEN)

Abstract Objectives Hemorrhagic rupture is a severe and potentially life-threatening complication of renal angiomyolipoma (AML). However, current clinical tools for accurately predicting hemorrhage risk remain limited. This study aimed to establish and validate a clinical nomogram for predicting hemorrhagic rupture in AML based on preoperative characteristics, and to investigate the underlying molecular correlates involving CD34, PPARG, and PTEN expression. Methods A total of 379 patients with AML and 40 normal kidney tissue samples (2010–2021) were retrospectively analyzed. Patients were temporally divided into a training cohort (n=285) and an independent temporal validation cohort (n=94). Independent clinical predictors of hemorrhagic rupture were identified through univariate and multivariate logistic regression and incorporated into a nomogram. Model performance was evaluated using receiver operating characteristic (ROC) analysis and calibration plots in the validation cohort. Additionally, immunohistochemistry, qPCR, and ELISA were conducted to assess CD34, PPARG, and PTEN expression to explore biological mechanisms associated with rupture. Results Tuberous sclerosis complex (TSC), tumor size ≥4 cm, rich vascular supply, and exophytic growth pattern were identified as independent predictors of hemorrhagic rupture (all p<0.05). The nomogram demonstrated excellent discrimination (AUC=0.967) and satisfactory calibration in the independent validation cohort. At the molecular level, immunohistochemical analysis revealed elevated CD34 and PPARG expression and reduced PTEN expression in AML compared with normal tissues (p<0.05). Consistently, qPCR and ELISA assays confirmed significant upregulation of CD34 and PPARG and downregulation of PTEN in hemorrhagic AML relative to non-hemorrhagic AML (p<0.001). Conclusions The developed nomogram serves as a reliable pre-operative tool for individualized risk stratification of AML rupture. Furthermore, the aberrant expression of CD34, PPARG, and PTEN provides mechanistic insights into the vascular remodeling and fragility underlying AML hemorrhage, suggesting potential targets for future therapeutic research.