From the Guidelines
Renal hypoperfusion can indeed cause increased capillary permeability in the kidney.
Key Mechanisms
- Renal hypoperfusion leads to a decrease in glomerular hydrostatic pressure, which can cause a decrease in glomerular filtration rate (GFR) 1.
- Angiotensin II (Ang II) production is increased in response to renal hypoperfusion, which constricts the efferent arteriole to a greater extent than the afferent arteriole, maintaining glomerular hydrostatic pressure and GFR 1.
- ACE inhibitor therapy can diminish Ang II formation and effect, leading to a decrease in GFR in patients with renal hypoperfusion 1.
Clinical Implications
- Patients with systemic hypotension, high-grade renal artery stenosis, extracellular fluid (ECF) volume contraction, or congestive heart failure (CHF) are at risk of developing renal hypoperfusion and increased capillary permeability 1.
- Vasoconstrictor agents, such as nonsteroidal anti-inflammatory agents (NSAIDs) or cyclosporine, can also precipitate renal hypoperfusion and increased capillary permeability in patients taking ACE inhibitors 1.
- Chronic renal insufficiency can lead to adaptive changes, including hyperfiltration, which can be reversed by ACE inhibitor therapy, resulting in an initial fall in GFR and rises in blood urea nitrogen and serum creatinine 1.
From the Research
Renal Hypoperfusion and Capillary Permeability
- Renal hypoperfusion can cause damage to the endothelium, leading to an increase in its prothrombotic and pro-adhesive properties, which can result in congestion in the microcirculation of the renal medulla 2.
- Impaired blood flow can cause the migration of pericytes and the disintegration of vessels, leading to peritubular rarefaction, which is attributed to the development of chronic kidney disease 2.
- Increased capillary permeability can lead to the loss of protein-rich fluid from the intravascular to the interstitial space, resulting in capillary leak syndrome, which can be caused by various diseases, including sepsis, and can lead to acute kidney injury 3.
- Renal microvascular disease involves alterations in endothelial barrier permeability, and evidence suggests that there is a microvascular component to the pathogenesis of renal scarring 4.
- Renal hypoperfusion is associated with an elevated renal arteriolar resistance and reductions in renal plasma flow and peritubular capillary blood flow, which can lead to tubulointerstitial disease and disease progression 5.
Mechanisms of Increased Capillary Permeability
- The increase in capillary permeability can be caused by the release of cytokines and other inflammatory mediators, which can damage the endothelial cells and increase the permeability of the capillaries 3, 6.
- The sphingosine-1-phosphate (S1P) receptor 1 agonist SEW2871 can reduce renal microvascular permeability and improve capillary perfusion in a mouse model of sepsis-induced acute kidney injury 6.
- The renal microvasculature is emerging as a key player in acute and chronic kidney diseases, and alterations in endothelial barrier permeability are a key component of renal microvascular disease 4.
Relationship Between Renal Hypoperfusion and Increased Capillary Permeability
- Renal hypoperfusion can lead to increased capillary permeability, which can result in capillary leak syndrome and acute kidney injury 2, 3.
- The reduction in peritubular capillary blood flow is inversely proportional to the degree of tubulointerstitial disease and tubular dysfunction, suggesting a link between renal hypoperfusion and increased capillary permeability 5.