Hyperfiltration and inner stripe hypertrophy may explain findings by Gamble and coworkers.

Simulations conducted in a mathematical model were used to exemplify the hypothesis that elevated solute concentrations and tubular flows at the boundary of the renal outer and inner medullas of rats may contribute to increased urine osmolalities and urine flow rates. Such elevated quantities at that boundary may arise from hyperfiltration and from inner stripe hypertrophy, which are correlated with increased concentrating activity (Bankir L, Kriz W. Kidney Int. 47: 7-24, 1995). The simulations used the region-based model for the rat inner medulla that was presented in the companion study (Layton AT, Pannabecker TL, Dantzler WH, Layton HE. Am J Physiol Renal Physiol 298: F000-F000, 2010). The simulations were suggested by experiments which were conducted in rat by Gamble et al. (Gamble JL, McKhann CF, Butler AM, Tuthill E. Am J Physiol 109: 139-154, 1934) in which the ratio of NaCl to urea in the diet was systematically varied in eight successive 5-day intervals. The simulations predict that changes in boundary conditions at the boundary of the outer and inner medulla, accompanied by plausible modifications in transport properties of the collecting duct system, can significantly increase urine osmolality and flow rate. This hyperfiltration-hypertrophy hypothesis may explain the finding by Gamble et al. that the maximum urine osmolality attained from supplemental feeding of urea and NaCl in the eight intervals depends on NaCl being the initial predominant solute and on urea being the final predominant solute, because urea in sufficient quantity appears to stimulate concentrating activity. More generally, the hypothesis suggests that high osmolalities and urine flow rates may depend, in large part, on adaptive modifications of cortical hemodynamics and on outer medullary structure and not entirely on an extraordinary concentrating capability that is intrinsic to the inner medulla.