Nanomedicine, Volume IIA: Biocompatibility

© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003 Geometrical Trapping in Kidney Vasculature

The kidney has the second highest specific blood perfusion rate of any organ, typically 70 mm3/sec-gm (~1300 cm3/min) up to a maximum of 100 mm3/sec-gm (~1800 cm3/min) (Table 8.4). Nevertheless, geometrical filtration of medical nanorobots from the renal blood flow is unlikely because the capillaries of kidney (also pancreas and intestine) have 50-70 nm fenestrations in the renal endothelium covering the mesangium [774, 2764-2766], far too small to allow either the formed blood elements or micron-scale medical nanorobots to pass through. The size, number, and density of these fenestrae are not markedly changed in human patients with acute renal failure [2767] although the fenestrae are smaller in spontaneously hypertensive rats [2768], and the diameter and number density of endothelial fenestrae may be purposely reduced by administration of aminoglycosides [2769, 2770] or certain perfusion chemicals [2771].

Experiments with microspheres using various animal models have investigated the largest sizes of inert spherical particles that can pass the kidney capillary bed without being trapped. In cats, microspheres 0.3-, 1.8- and 3.5-microns in diameter readily passed through feline kidney [2772]. In dogs, one experiment found that 3-30% of renally-injected microspheres <7 microns in diameter reached the renal vein, whereas microspheres >10 microns in diameter were completely trapped within the preglomerular or glomerular circulation [2773]. Other studies found that 9-micron microspheres are not entirely trapped in canine renal cortex [2774-2776], and that previously trapped 9-micron microspheres can be released due to subsequent vasodilation caused by the presence of the particles themselves [2774, 2775]. (Sepsis also results in renal vasodilation [2777] which could in theory allow slightly larger particles to pass – an important point to note when performing a nanomedical procedure on a patient with sepsis.) Progressively larger microspheres may pass during hypotension due to vasodilation, but microspheres >~15 microns in diameter are trapped in canine [2778] and rat [2779] renal arterioles. Canine renal vasa rectae vessels are typically 10-20 microns in diameter [2780] and the average kidney afferent arteriole diameter is ~16 microns [2781]. In one study [2781], the mean diameter of spheres trapped in the interlobular arteries was ~26 microns. Finally, injections of 40- to 150-micron and 100- to 300-micron dextran microspheres caused canine renal embolism with dramatic occlusion of blood vessels using even small quantities of particles [2782]. In rats, 8- to 12-micron microspheres were completely extracted from the bloodstream by the kidney [2783-2785], though in one study not all 15-micron spheres were trapped in renal glomeruli [2786] and in another study 15-micron microspheres injected intracardially proved capable of locally dilating preglomerular vessels and slowly migrating towards the glomeruli [2787]. In rabbits, 15-micron microspheres lodged in renal glomerular capillaries and 25-micron microspheres blocked interlobular arteries causing intrarenal hemorrhage [2788]. Renal clearance of creatinine was unaffected at a total injection dose of 1 x 105 15-micron particles but was detectably decreased at 2 x 105 particles and markedly decreased at 5 x 105 particles [2788].

Arteriovenous shunting around the renal filtration bed could in principle allow the continuous circulation of somewhat larger nanorobots, but such shunting is generally not available in the kidneys of healthy subjects. Some arteriovenous renal shunting [2789], marked by the passage of 10- to 30-micron microspheres, is seen in rats [2790] and humans [2791-2796] but only in connection with renal transplants [2790, 2791], renal biopsies [2792, 2793], and renal carcinomas [2794-2796], the latter producing volumetric shunt rates ranging from 15-57% [2795].


Last updated on 30 April 2004