Concentration of solutes in the renal inner medulla: interstitial hyaluronan as a mechano-osmotic transducer

Abstract

. Concentration of solutes in the renal inner medulla: interstitial hyaluronan as a mechano-osmotic transducer. Am J Physiol Renal Physiol 284: F433-F446, 2003; 10.1152/ajprenal.00067.2002Although the concentrating process in the renal outer medulla is well understood, the concentrating mechanism in the renal inner medulla remains an enigma. The purposes of this review are fourfold. 1) We summarize a theoretical basis for classifying all possible steady-state inner medullary countercurrent concentrating mechanisms based on mass balance principles. 2) We review the major hypotheses that have been proposed to explain the axial osmolality gradient in the interstitium of the renal inner medulla. 3) We summarize and expand on the SchmidtNielsen hypothesis that the contractions of the renal pelvocalyceal wall may provide an important energy source for concentration in the inner medulla. 4) We discuss the special properties of hyaluronan, a glycosaminoglycan that is the chief component of a gel-like renal inner medullary interstitial matrix, which may allow it to function as a mechanoosmotic transducer, converting energy from the contractions of the pelvic wall to an axial osmolality gradient in the medulla. These considerations set the stage for renewed experimental investigation of the urinary concentrating process and a new generation of mathematical models of the renal concentrating mechanism, which treat the inner medullary interstitium as a viscoelastic system rather than a purely hydraulic system. glycosaminoglycans; renal pelvis; vasopressin; hyaluronan IN STATES OF FLUID DEPRIVATION or nonrenal water loss, the kidney can conserve water while maintaining excretion of solutes. It does this by concentrating the solutes in the urine to osmolalities that markedly exceed the osmolality of plasma. A large number of studies, exemplified by the data shown in Fig. 1, have demonstrated that the urinary concentrating process is associated with the generation of a corticomedullary osmolality gradient in the medullary tissue, oriented with the maximum osmolality in the deepest part of the inner medulla, i.e., at the papillary tip. The classic micropuncture studies of Gottschalk and Mylle (17) have established that the medullary hypertonicity is due to solute accumulation in all structures in the medulla, including loops of Henle, vasculature, and collecting ducts. The high medullary interstitial osmolality provides a driving force for osmotic water flow across the collecting ducts, which are rendered permeable to water through the action of vasopressin (33). The high water permeability allows osmotic equilibration of urine with the medullary interstitial fluid.In 1959, Kuhn and Ramel (43) proposed a model to explain concentration of solutes in the renal medulla Address for reprint requests and other correspondence: M. A. Knepper,

Calcium Oxalate Crystal Adherence to Hyaluronan-, Osteopontin-, and CD44-Expressing Injured/Regenerating Tubular Epithelial Cells in Rat Kidneys

“…In the kidney, HA is normally not expressed at the luminal surface of tubular cells and is present only in the medullary interstitium, where it provides structural stability to the tubules and contributes to concentrating the urine (12). HA expression in the renal cortex is upregulated in renal inflammatory diseases such as interstitial nephritis (13), acute ischemic injury (14,17), autoimmune renal injury (15), and acutely rejecting human kidney grafts (16).…”

“…OPN and CD44 were also quantified in the remaining part of the medulla, by analyzing six randomly chosen microscopic fields of the ISOM and inner medulla. HA was not quantified in this region, because the well known abundant amount of HA in the interstitium of the inner medulla stains nearly the entire tissue (12).…”

“…In the kidney, HA is hardly detectable in the cortex but is abundantly present as the main component of the renal inner medullary interstitium (12). HA in the kidney is upregulated during various inflammatory disease states (13)(14)(15)(16)(17).…”

Ectopic fat storage in heart, blood vessels and kidneys in the pathogenesis of cardiovascular diseases

“…Compression of the inner medulla is likely since it is not protected by the renal fibrous capsule that corsets the entire kidney. Intriguingly, the content of interstitial hyaluronan, a space filling molecule normally found in the renal inner medulla, 59 is markedly increased in obese dogs 60 and rabbits. 61 The expansion of the hyaluronan-filled extracellular matrix between vasa recta and thin Henle tubules, evidenced with PAS and Alcian blue staining on histological section of the medulla, 61 may thus contribute to the compression of medullary structures.…”

Urine-Concentrating Mechanism in the Inner Medulla

“…Moreover, no experimental data support the production or addition of such an osmolyte in the IM. Schmidt-Nielsen (33) suggested that contractions of the pelvic wall could serve as a source of energy for the inner medullary concentrating process, and Knepper and his colleagues (34) postulated that hyaluronan could act as a transducer to convert the mechanical energy of the contractions into a concentrating effect. However, this conversion has not yet been shown to be thermodynamically feasible, and there are no experimental measurements of such a process in the IM.…”