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Effect of Flow Rate and the Extracellular Fluid Volume on Proximal Urate and Water Absorption

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Effect of Flow Rate and the Extracellular Fluid Volume on Proximal Urate and Water Absorption View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Kidney International, Vol. /7(1980), pp. 155 -16/ Effect of flow rate and the extracellular fluid volume on proximal urate and water absorption HARRY 0. SENEKJIAN, THOMAS F. KNIGHT, STEVEN C. SANSOM, and EDWARD J. WEINMAN Rena! Section, Department of Internal Medicine, Veterans Ad,ninist ration Medical Center and Baylor College of Medicine, Houston, Texas Effect of flow rate and the extracellular fluid volume on proximal laboratory. It has been demonstrated previously urate and water absorption. The in vivo microperfusion tech- nique was used to examine the effect of variations in tubular flow that the state of hydration of the extracellular fluid rate and the extracellular fluid volume on [2-14C]-urate and water volume (ECV) affects urate transport [1—4]. Spe- absorption in the proximal tubule of the rat. In nondiuretic ani- cifically, expansion of the ECV with isotonic saline mals, fractional urate absorption was highest at the lowest per- fusion rate examined and decreased as the rate of perfusion was resulted in an increase in urate excretion and an in- increased. Increasing the initial concentration of urate in the per- creased recovery of radioactive urate microinjected fusion solution had no effect on the fractional absorption of directly into the proximal tubule [1]. By analogy to urate. Fractional water absorption was also inversely related to the rate of perfusion. Expansion of the extracellular fluid volume the known changes in sodium reabsorption induced with isotonic saline resulted in rates of urate absorption similar by expansion of the ECV, we suggested a possible to control values at any given microperfusion rate. Fractional link between the reabsorption of sodium and that of water absorption showed the same flow rate dependency pattern observed in control animals, but at a significantly lower rate of urate. Other studies, however, indicated that the tu- absorption. These studies indicate that fractional urate absorp- bular absorption of sodium and water can be disso- tion is dependent upon some parameter of tubular flow rate and ciated from that of urate [5,6].We felt it important, that the relationship between urate absorption and perfusion rate is not related to the delivered load of urate per se and is not therefore, to reexamine the mechanism by which affected by the state of hydration of the extracellular fluid. alterations in the ECV affect urate transport. We also wished to examine the influence of flow rate on Effet du debit tubulaire et du volume des liquides extra-cellulaires sur Ia reabsorption proximale d'urate et d'eau. La microperfusion water reabsorption in the proximal convoluted in vivo a etC utilisée pour Ctudier l'effet des variations du debit tubule. tubulaire et du volume extra-cellulaire sur Ia reabsorption d'urate 2-'4C et d'eau dans le tube proximal du rat. Chez les ani- Methods maux non diurétiques, Ia reabsorption fractionnelle d'urate est Ia plus grande aux debits de perfusion les plus faibles utilisés et All studies were performed in male Sprague- diminue quand Ic debit de perfusion est augmentC. L'aug- Dawley rats anesthetized i.p. with pentobarbital so- mentation de Ia concentration initiale d'urate dans Ia solu- tion perfusCe n'a pas d'effet sur Ia reabsorption fractionnelle. La dium (50mg/kgbody wt) and prepared for micro- reabsorption fractionnelle d'eau est aussi en fonction inverse du puncture as previously described [5].Eachanimal debit de perfusion. L'expansion du volume des liquides extra- received an infusion of isotonic saline equal to 1% cellulaires avec du chlorure de sodium isotonique a pour effet des debits de reabsorption d'urate semblables aux valeurs contrôles of body wt as replacement for surgical losses of a tous les debits de microperfusion. La reabsorption fraction- fluid. nelle d'eau reste dCpendante du debit de perfusion, comme chez Proximal tubule microperfusion studies were per- les animaux témoins, mais a des niveaux inférieurs de reabsorp- tion. Ces résultats indiquent que Ia reabsorption fractionnelle formed with the Hampel microperfusion apparatus d'urate est dépendante d'un paramètre lie au debit tubulaire et as previously described [5].[2-'4C]-urate(specific que Ia relation entre Ia reabsorption d'urate et le debit de per- activity, 300tCiJrng)(Amersham Searle Corp., Ar- fusion n'est pas due au debit d'urate délivré et n'est pas modifiée par l'état d'hydratation du liquide extracellulaire. lington Heights, Illinois) was dissolved initially in a Received for publication November 21, 1978 The determinants of the absorptive flux for urate and in revised form May 29, 1979 from the proximal tubule of the rat kidney have 0085-2538/80/0017—0155 $01.40 been under investigation in recent studies from this © 1980 by the International Society of Nephrology 155 156 Senekjian et a! solution containing sodium chloride (120 mEq/liter) Fractional water absorption (%/m,n tubule) =(I— and sodium bicarbonate (30 mEq/liter). An aliquot PF/CF1)x 100 X length of perfused tubule-' (2) of this solution was added to a 0.9-g/dl solution of sodium chloride containing [methoxy-3HJ-inulin Fractional urate absorption (%/mm tubule) =(1— (New England Nuclear Corp., Boston, Massachu- CFIPFurateICFIPF1n) x100 x length of perfused setts) to achieve a final urate concentration of 1.3 tubule (3) mg/dI. This concentration was confirmed by a un- case method with a glucose analyzer (Beckman In- The relationship between the fractional rates of struments Inc., Fullerton, California). The solution absorption of urate and water and the rate of per- was equilibrated with carbon dioxide, and the final fusion were represented by an exponential equation pH was 7.4. Where examined, unlabeled urate (final in the form: concentration of 10 mg/dl) or probenecid (2.8 mg/dl) was added to the perfusion solution. Following each Y =PIe2x microperfusion, the tubule was filled with a latex cast, and the distance between the perfusion and where e is the natural logarithm, x is the perfusion collecting sites was determined by microdissection rate, y is the fractional rate of absorption, and P1 after maceration of the kidney in hydrochloric acid. and P2 are coefficients that were estimated by the The effects of alterations in the perfusion rate on method of nonlinear least squares [7]. Statistical urate absorption were determined in 8 nondiuretic significance was determined using the Fisher test and 7 volume-expanded animals. The nondiuretic and Student's t test for unpaired data. rats received an i.v. infusion of saline at the rate of 1.2 mllhr throughout the study. Volume-expanded Results animals were infused with a volume of isotonic sa- The individual data points relating the fractional line equal to 10% of body wt over a 60-mm interval, absorption of urate and water, expressed as percent after which the infusion rate was adjusted to match per millimeter of perfused tubule length, to the mi- the urine flow rate. Isotonic saline containing 1.3 croperfusion rate in nondiuretic animals are sum- mgldl urate was used as the perfusion solution in marized in Table I and Fig. 1. As shown in Fig. 1, these studies. In 4 additional animals (2 nondiuretic fractional urate absorption was highest at the lowest animals and 2 volume-expanded animals), the mi- perfusion rates examined and decreased as the per- croperfusion solution was normal saline containing fusion rate was increased. The relationship between 1.3 mg/dl urate plus probenecid in a concentration the fractional rate of urate absorption and the per- of 2.8 mg/dl. In each group of studies, the rate of fusion rate is best described by the nonlinear regres- perfusion was altered by changing the speed of the sion equation y =29.7e_O0818x.Water absorption microperfusion pump. showed a marked perfusion rate dependency over a To examine the effect of increased urate concen- range of perfusion rates from 5 to 15 nllmin. At per- tration, we studied an additional 11 animals under fusion rates from 20 to 37 nI/mm, however, the frac- nondiuretic conditions. In these studies, the micro- tional rate of water absorption tended to decline on- perfusion solutions contained an initial concentra- ly slightly as a function of the perfusion rate. The tion of urate of either 1.3 or 10 mgldl. regression equation relating fractional water ab- Radioactivity of microperfusion solutions and sorption to the perfusion rate is y =4l.2e_o0432x. collected perfusate was measured in Biofluor (New To determine if the decrease in the fractional ab- England Nuclear) in a Tri-carb liquid scintillation sorption of urate with increasing rates of perfusion counter (Packard Instruments Co., Downers was a function of the perfusion rate itself or was a Grove, Illinois). Counts per minute were converted secondary consequence of the increased delivered to disintegrations per minute after corrections for load of urate, we performed additional studies with a quench, efficiency of counting, and crossover perfusion solution containing urate in an initial con- counts. For each microperfusion, the following cal- centration of 10 mg/dl. These results were com- culations were made: pared to a separate group of control observations that used a perfusion solution containing urate in a Perfusion rate (ni/mi,,) =CF/PF1x collected concentration of 1.3 mg/dl (Fig. 2). With the control volume X min' (I) solution, the relationship between fractional urate absorption and the rate of perfusion
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