Preeclampsia-associated nephropathy; current insights into renal histopathology and molecular mechanisms

Abstract

Preeclampsia-associated nephropathy represents a distinct form of pregnancy-induced kidney injury characterized by proteinuria, hypertension, and endothelial dysfunction, posing significant risks to both maternal and fetal health. Historically defined by the hallmark lesion of glomerular endotheliosis, contemporary histopathological analyses have expanded this paradigm to reveal widespread podocyte effacement, mesangial expansion, and subtle tubulointerstitial alterations that correlate with disease severity and postpartum renal recovery trajectories. At the molecular level, recent insights emphasize a profound angiogenic imbalance driven by excessive placental release of anti-angiogenic factors, particularly soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin, which disrupt glomerular capillary integrity and impair endothelial nitric oxide signaling. Concurrently, oxidative stress, complement activation, and dysregulated inflammatory cascades amplify endothelial injury, while emerging evidence highlights mitochondrial dysfunction and epigenetic modifications as critical contributors to sustained podocyte damage and maladaptive repair. Integrative multi-omics approaches have further identified dysregulated lipid metabolism, extracellular matrix remodeling, and autophagy impairment as pivotal pathways linking systemic vascular stress to localized nephropathy. Despite these advances, the precise temporal sequence of molecular events and their translation into targeted therapeutics remain unresolved. Current research is increasingly focused on biomarker validation, noninvasive imaging correlates, and repurposing angiogenic or complement-modulating agents to mitigate renal injury. Translational efforts are now prioritizing interventions that restore vascular homeostasis and preserve podocyte architecture, alongside longitudinal cohorts designed to delineate long-term renal sequelae. Finally, a deeper mechanistic understanding of preeclampsia-associated nephropathy refines risk stratification, informs postpartum monitoring, and illuminates broader paradigms of endothelial-driven kidney disease across the lifespan.

Keywords: Kidney disease, Nephropathy, Preeclampsia, Hypertension, Renal histopathology