Increased Intracapsular Pressure
Increased pressure within the renal parenchyma can result from increased volume in the kidney caused by increased interstitial fluid in HF, in the context of an organ (the kidney) that cannot expand in volume (Central Illustration).
Increased Intracapsular, Perirenal, and Intra-Abdominal Pressures
Above, effect of intrarenal congestion. As fluid exits the bloodstream, pressures rise within the rigid renal capsule, compressing the tubules and the intrarenal venules. Below left, consequences to the perirenal adipose tissue, leading mainly to compression of renal vasculature. Below right, kidneys in the retroperitoneal space. The weight of the fat or fluid in this compartment compresses the renal vasculature.
Histologically, the fibrous renal capsule consists of many collagen fibers in a dense, irregular structure, making it decidedly rigid. Pressures up to 10,000 mm Hg are required to stretch the capsule to twice its size or even rupture it (Figure 1, no 6). Pressures of such a magnitude are generally reached only during traumatic events or polycystic kidney disease.[14,15] In other instances, such as congestion from HF, pressures are likely deflected inward by the rigid capsule. To illustrate, in HF (with both reduced and preserved ejection fraction), as a result of maladaptive water and sodium homeostasis, intravascular pressures rise. As intravascular pressures reach a tipping point, fluid will exit the bloodstream into the interstitium. In the skin, this gives pitting edema; in the lungs, it leads to alveolar edema. Interstitial edema is similarly present in the kidneys, albeit less visible. The kidneys, however, do not have the ability to expand as do the skin and subcutaneous tissue. The reason for this lack of expandability is the presence of the very rigid renal capsule (Figure 1, number 6).
Several kidney congestion models in rats and dogs have demonstrated that when central or renal vascular pressures are increased, usually from clipping of the respective vein, renal interstitial pressures rise collinearly.[17,18] Moreover, GFR and urinary production almost instantly decrease. In addition, clipping of the renal vein induces proteinuria, reflecting (pressure-induced) damage the Bowman capsule.
Two studies independently examined renal perfusion in a congested kidney model and found diminished perfusion of the renal medulla but not the renal cortex.[18,19] Anatomically, this means the tubules are more at risk for damage from congestion than are the glomeruli. This is further supported by the notion that intrarenal expression of biomarkers of tubular damage, in particular KIM-1 and osteopontin, were increased in a murine model of renal congestion. Even more interestingly, the expression of these biomarkers was attenuated by removing the capsule before inducing congestion.
In addition to tubules and glomeruli, veins are also affected by intracapsular pressure overload, as has been demonstrated in several small ultrasound studies in humans.[21–23] In the healthy kidney, venous blood flow is minimally altered by hemodynamic changes. However, increases in pressure within the renal capsule will lead to a collapsing of renal veins because the capsule prohibits the kidney from expanding, and pressures are reflected inward. On ultrasonography, a discontinuous venous flow pattern can be recognized; this pattern is correlated with clinical signs and symptoms of congestion. This indicates that in the congested kidney, blood is solely being pulled through a compressed vein during diastole.
In summary, interstitial congestion of the kidney, combined with the inability for the interstitium to expand because of the renal capsule, compresses intrarenal structures such as veins, glomeruli, and tubules, diminishing their function.
JACC Heart Fail. 2022;10(3):175-183. © 2022 American College of Cardiology Foundation