Cycles and separations in a model of the renal medulla

This study gives the first quantitative analysis of net steady-state transmural fluxes of water, urea, and NaCl in a numerical model of the rat renal medulla in antidiuresis, revealing the model's predictions of water, urea, and NaCl cycling patterns. These predictions are compared both to in vivo micropuncture data from the literature and to earlier qualitative proposals (e.g., K. V. Lemley and W. Kriz. Kidney Int. 31: 538-548, 1987) of cycling and exchange patterns based on medullary anatomy and available permeability and transport parameter measurements. The analysis is based on our most recent three-dimensional model [X. Wang, S. R. Thomas, and A. S. Wexler. Am. J. Physiol. 274 (Renal Physiol. 43): F413-F424, 1998]. In general agreement with earlier proposed patterns, this analysis predicts the following: 1) important water short-circuiting from descending structures to ascending vasa recta in most medullary regions, 2) massive urea recycling in the upper inner medulla, 3) a progressive increase of the ratio of urea to total osmoles along the corticopapillary axis, 4) urea dumped from the collecting ducts (CD) into the deep papilla is returned to the cortex essentially via outer medullary short vasa recta, bearing witness to a shift from the long descending limbs and vasa recta of the inner medulla (IM) to short structures in the outer medulla (OM). The analysis also shows that the known radial heterogeneity of the inner stripe (IS) implies unequal osmolalities in long descending limbs, vasa recta, and CDs entering the IM across the OM/IM border and explains the model's unorthodox osmolality profile along the CD. In conflict with micropuncture evidence of a doubling of urea flow in superficial Henle's loops (SHL) between the end proximal and early distal tubule (T. Armsen and H. W. Reinhardt. Pflügers Arch. 326: 270-280, 1971), the model predicts net urea loss from SHL due to the model's inclusion of nonneglible measured urea permeability of medullary thick ascending limbs [M. A. Knepper, Am. J. Physiol. 245 (Renal Fluid Electrolyte Physiol. 14): F634-F639, 1983]. We present a suite of adjusted model permeabilities that improves agreement with the micropuncture data on this point. In conclusion, this modeling analysis of solute and water recycling serves as a quantitative check on qualitative propositions in the literature and allows closer critical comparison of model behavior with published experimental results than was heretofore possible.