Maryam Kazemi
1 
, Arina Shikarchi
2 , Azam Moridi
3 , Mahnaz Kayyal
4 , Zahra Hamidi Madani
5 , Sadaf Rassouli
6 , Zeinab Zamanpour
7 , Nazanin Farzaneh
8* 1 Department of Obstetrics and Gynecology, Imam Hossein Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
2 Women’s Health Research Center, Islamic Azad University of Medical Sciences, Tabriz Branch, Tabriz, Iran
3 Mother and Child Welfare Research Center, Hormozgan University of Medical Science, Bandar Abbas, Iran
4 Department of Nursing, Shahid Mostafa Khomeini Hospital of Tabas, Birjand University of Medical Sciences, Birjand, Iran
5 Department of Obstetrics and Gynecology, Reproductive Health Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
6 Department of Gynecology and Obstetrics, Imam Khomeini Hospital, School of Medicine, Sari University of Medical Sciences, Sari, Iran
7 Department of Gynecology and Obstetrics, Fertility, Infertility, and Perinatology Research Center, Jundishapur University of Medical Sciences, Ahvaz, Iran
8 Department of Obstetrics and Gynecology, Taleghani General Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Science, Tehran, Iran
Abstract
The intricate triad of placenta, platelets, and podocytes represents a central framework for understanding the multifactorial renal injury associated with antiphospholipid syndrome (APS) during pregnancy. This triadic interaction underscores a pathophysiological continuum driven by thrombosis, inflammation, and endothelial dysfunction that disrupts both placental and renal homeostasis. In pregnant women with APS, the placenta functions as a key initiator of systemic disturbances through procoagulant and proinflammatory mediators that alter vascular tone and promote immune activation. These placental signals propagate into the maternal circulation, stimulating platelet activation and aggregation that intensify microvascular thrombotic damage. Activated platelets further contribute to endothelial injury by releasing cytokines, chemokines, and growth factors that perpetuate inflammatory cascades and coagulative imbalance. At the renal glomerular level, podocytes serve as critical yet vulnerable responders within this network. They experience direct insults from circulating antiphospholipid antibodies and secondary injury from ischemic and hemodynamic stress induced by microthrombi and endothelial derangement. The consequent podocyte depletion and barrier disruption lead to proteinuria and progressive glomerular dysfunction characteristic of APS nephropathy. This integrative model highlights how maternal, hematologic, and renal compartments intersect in a self-reinforcing cycle of injury, illuminating potential therapeutic targets that modulate platelet activation, placental inflammation, and podocyte resilience.
Implication for health policy/practice/research/medical education:
The conjunction of placental insufficiency, platelet hyperactivity, and podocyte injury creates a vicious cycle of kidney injury in pregnant women with APS. Placental thrombosis and ischemia release antiangiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1), which further impair endothelial function and podocyte integrity. Platelet-derived microparticles exacerbate this injury by promoting inflammation and coagulation within the glomeruli. Podocyte loss, in turn, leads to proteinuria and nephrotic syndrome, which can worsen hypertension and further compromise placental perfusion.
Please cite this paper as: Kazemi M, Shikarchi A, Moridi A, Kayyal M, Hamidi Madani Z, Rassouli S, Zamanpour Z, Farzaneh N. Placenta, platelets, and podocytes; the triad of renal injury in pregnant women with antiphospholipid syndrome. J Nephropharmacol. 2025;14(x):e12823. DOI: 10.34172/npj.2025.12823.