Targeted delivery of solutes and oxygen in the renal medulla: role of microvessel architecture

Abstract

Renal medullary function is characterized by corticopapillary concentration gradients of various molecules. One example is the generally decreasing axial gradient in oxygen tension (Po2). Another example, found in animals in the antidiuretic state, is a generally increasing axial solute gradient, consisting mostly of NaCl and urea. This osmolality gradient, which plays a principal role in the urine concentrating mechanism, is generally considered to involve countercurrent multiplication and countercurrent exchange, although the underlying mechanism is not fully understood. Radial oxygen and solute gradients in the transverse dimension of the medullary parenchyma have been hypothesized to occur, although strong experimental evidence in support of these gradients remains lacking. This review considers anatomic features of the renal medulla that may impact the formation and maintenance of oxygen and solute gradients. A better understanding of medullary architecture is essential for more clearly defining the compartment-to-compartment flows taken by fluid and molecules that are important in producing axial and radial gradients. Preferential interactions between nephron and vascular segments provide clues as to how tubular and interstitial oxygen flows contribute to safeguarding active transport pathways in renal function in health and disease.

Renal Hypoxia: An Important Prognostic Marker in Patients with Chronic Kidney Disease

“…The presence of renal hypoxia in patients with CKD is attributed to renal fibrosis and vasoconstriction induced by a variety of risk factors [19]. The architecture and oxygen metabolic processes of the kidney contribute to the low oxygenation of the renal medulla [20]. This physical characteristic of the kidney supports our finding that the MR2* values were higher than the CR2* values in patients with CKD as well as healthy controls.…”

Hypoxia and Mucosal Inflammation

“…Given the steep O 2 gradient due to countercurrent blood flow, colonic and renal medullary epithelia exist at very low pO 2 (24). These cells have proven to be remarkably resistant to hypoxia; even very low levels of oxygenation allow them to function normally (25, 26). The importance of HIF to epithelial function was originally shown by microarray analysis of intestinal epithelial cells cultured under low-O 2 conditions (pO 2 ~ 20 mm Hg) (15).…”

Renal oxygenation: From data to insight

“…In the outer medulla the vascular bundles have a specific radial topography, with the long descending vasa recta destined for the inner medulla being sequestered into the core of the vascular bundles, while short vasa recta supplying the outer medulla are in the periphery of the vascular bundles (Figure ). Furthermore, the oxygen consuming tubular elements in the outer medulla, the thick ascending limbs of the loop of Henle (mTALH) and the collecting ducts (CD), are situated chiefly in the inter‐bundle region, at some distance from the long descending vasa recta . In the inner medulla of the rat, each CD is surrounded by closely associated ascending vasa recta, with clusters of descending vasa recta more distant to the CD .…”

“…Furthermore, the oxygen consuming tubular elements in the outer medulla, the thick ascending limbs of the loop of Henle (mTALH) and the collecting ducts (CD), are situated chiefly in the inter-bundle region, at some distance from the long descending vasa recta. 55,56 In the inner medulla of the rat, each CD is surrounded by closely associated ascending vasa recta, with clusters of descending vasa recta more distant to the CD. 57,58 In a series of modelling studies of increasing complexity, Layton and Edwards and their colleagues examined the impact of this topography on oxygenation of the outer and inner medulla (multiple publications discussed below).…”