What is the function of podocytes in the kidneys?

Function of Podocytes in the Kidneys

Podocytes are highly specialized epithelial cells that form the final structural and functional barrier of the glomerular filtration system, preventing protein loss into urine through their unique foot processes and slit diaphragms while maintaining glomerular capillary integrity. 1, 2

Primary Structural Functions

Filtration Barrier Formation

• Podocytes wrap around glomerular capillaries with interdigitating foot processes that create the slit diaphragm, serving as the ultimate barrier to urinary protein loss 2, 3
• The cells cover the outer layer of the glomerular basement membrane (GBM) and work in conjunction with glomerular endothelial cells to regulate filtrate from circulating blood 1, 2
• Podocytes are negatively charged, which is essential for maintaining the glomerular filtration barrier through electrostatic repulsion of negatively charged plasma proteins like albumin 4
• The negative charge works with size-selective properties (pores approximately 6 nm) to prevent passage of plasma proteins under normal conditions 4

Mechanical Support

• Terminally differentiated podocytes must cover the glomerular capillary surface area, and their density directly affects mechanical support of the capillary 5
• Lower podocyte density reduces mechanical support and heightens susceptibility to barotrauma with high intraglomerular capillary pressures 5
• As glomerular diameter increases (such as with obesity), podocytes must cover larger surface areas, which can lead to proteinuria when podocyte density decreases 5

Signaling and Communication Functions

Orchestration of Glomerular Repair

• Podocytes produce critical angiogenic factors including VEGF and Angiopoietin-1 (Ang-1), which orchestrate glomerular capillary repair and maintenance 5
• Signals from podocytes attract sprouting of capillaries to sites beneath the GBM; where GBM is devoid of podocytes, capillaries never assemble 5
• The appropriate level of VEGF from podocytes is crucial—both overexpression and deletion cause proteinuria and pathologic changes in glomerular endothelial cells 5

Cell-Cell Communication Hub

• Podocytes serve as a central hub for communication in the kidney, mediating cross-talk between glomerular and non-glomerular cells under both basal conditions and cellular stress 1
• Podocyte-derived extracellular vesicles can be internalized by tubular cells, representing a novel form of glomerular-tubular communication 5
• Treatment of tubular epithelial cells with podocyte-derived EVs induces a profibrotic phenotype, demonstrating functional signaling capacity 5

Clinical Significance

Podocyte Injury and Disease

• Podocyte injury and subsequent loss is the hallmark of many glomerular diseases (podocytopathies), including minimal change disease, focal segmental glomerulosclerosis, diabetic nephropathy, and lupus nephritis 2, 3
• In disease states like minimal change disease, disruption of the negative charge allows larger structures up to 70 nm to pass through the barrier 4
• Chronic podocyte injury causes detachment from the GBM, leading to glomerulosclerosis and progression to end-stage kidney disease 2, 3

Nuclear YAP Localization

• Podocytes display predominant nuclear localization of YAP (Yes-associated protein), which is critical for podocyte survival 6
• Sequestration of YAP into the cytoplasm results in induction of apoptosis, affecting genes involved in cell-cell junction, extracellular space composition, and cell migration 6

Key Clinical Pitfalls

• Podocytes are postmitotic cells with limited regenerative capacity, making any injury potentially irreversible and emphasizing the importance of early intervention 1
• The extent of podocyte injury and its reversibility have major implications for treatment and prognosis in glomerular diseases 7
• In obesity with reduced nephron mass, podocytes face increased stress from having to cover larger glomerular surface areas while maintaining filtration barrier integrity 5