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Am J Physiol Renal Physiol 284: F433-F446, 2003; doi:10.1152/ajprenal.00067.2002
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Vol. 284, Issue 3, F433-F446, March 2003

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

Mark A. Knepper1, Gerald M. Saidel2, Vincent C. Hascall3, and Terry Dwyer4

1 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892; 2 Department of Biomedical Engineering, Case Western Reserve University, Cleveland 43560; 3 Department of Biomedical Engineering, The Cleveland Clinic Foundation, Cleveland, Ohio 44195; and 4 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216

Although 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 Schmidt-Nielsen 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 mechano-osmotic 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


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