Mathematical model of renal regulation of urea excretion

A mathematical model of transport processes in the ascending limbs (a.l.), collecting ducts (c.d.), and surrounding interstitium-capillary plexus (i.c.p.) of the renal medulla has been developed and applied to an investigation of mechanisms which may be involved in renal tubular regulation of urea excretion. Solute and water balance equations for perfectly-mixed compartments in series describe the transport processes in the a.l., c.d., and i.c.p. Solute species considered are urea, salt (NaCl), and an idealised ‘nonreabsorbable solute’ which accounts for miscellaneous substances accumulated in the c.d. The membrane transport equations used in the model describe solute movement by passive diffusion, solvent drag, and active transport; and water movement by osmosis. Model parameters are evaluated from published experimental data. Digital computer solutions of the model equations indicate that virtually all experimental observations pertaining to the regulation of urea excretion can be explained by an increase in the solvent drag of urea from the cortical and medullary c.d. Therefore, the need to postulate an active transport of urea from the c.d. to explain the regulation of urea excretion is obviated.     

The adaptation of renal urea excretion after unilateral nephrectomy and after overloading with urea

Summary Urea and inulin clearances were measured in unanesthetized rats 5 and 50 h, and 2–3 weeks after unilateral nephrectomy. At identical i-v infusion rates, urine flow in the uninephrectomized animals was similar to that of sham-operated controls. In the low range of urine flow rates, fractional urea excretion was higher in recently uninephrectomized animals than in controls. The increase appeared to be the consequence of the increased fractional excretion of water. At higher rates of urine flow, and after large loads of urea, the single kidney excreted urea in a manner similar to that of control kidneys. Urea clearances were, in 148/150 clearance determinations, lower than the simultaneously measured inulin clearances. A large increase of GFR was observed in rats chronically loaded and acutely infused with urea.Supported by Fonds National Suisse de la Recherche Scientifique, Grant No. 3440.70.     

Estimation of empty body water in steers by urea dilution

Urea dilution has been proposed as a practical method for estimating body composition in live cattle. The objectives of this study were to evaluate the urea dilution technique by comparing urea space to direct measurement of empty body water in steers and to develop prediction equations for empty body water in live steers using urea space parameters. Urea space was determined in 68 mixed-breed and 50 Angus steers ranging in live weight from 210 to 517 kg by the measurement of change in plasma urea nitrogen concentration before and 12 minutes after the midpoint of an intravenous infusion of 130 mg urea (20% solution w/v in 0.9% saline infused over 2 minutes) per kg live weight. Water in ground samples from carcass and digesta-free non-carcass fractions was determined by lyophilization. Linear relationships for pooled data of both groups of steers existed between empty body water and urea space (r = 0.96, P less than 0.001). Prediction of empty body water in live steers was improved by including live weight as an independent variable in a multiple regression equation (Sy X x = 7.2 kg for pooled data). Live weight alone predicted empty body water with a standard error of the estimate 36% larger than the multiple regression prediction using urea space and live weight.     

Role of sodium and urea in the renal concentrating mechanism inPsammomys obesus

Summary Micropunctures were performed at the tip of Henle's loops and vasa recta accessible at the extrarenal surface of the papilla in a desert rodent (Psammomys obesus) studied under mild NaCl (NaCl 4%, 0.0375 ml/min) and mild urea (urea 4%, 0.0375 ml/min) loading conditions.In NaCl loaded animals, it was confirmed that solute addition (mainly sodium) contributes in a large proportion to the concentrating process along the thin descending limb. Comparison of sodium and urea concentrations in the loops with those in vasa recta at the same level of the papilla demonstrated that 1. the transepithelial sodium gradient was compatible with a diffusion transport of this ion from the interstitium to the thin descending limb; 2. the sodium concentration higher in interstitium than in the loop fluid was not compatible with the existence of a purely passive concentrating process in inner medulla as was recently proposed [8], 3. the transepithelial urea gradient was very limited which indicates that this solute does not play an important part in the concentrating process.In urea loaded psammomys, solute addition (mainly urea) to the thin descending limb fluid was still present but water abstraction was enhanced as compared to salt loaded animals, probably on account to the higher interstitial urea concentration. It is, thus, brought to evidence that the relative contribution of water abstraction and solute addition to the concentrating process along the thin descending limb can vary in a given species as a function of the physiological state.     

Familial azotemia. Impaired urea excretion despite normal renal function

We performed detailed studies of renal function in two of five related patients with normal serum creatinine levels to determine the mechanism of their chronic azotemia. Inulin and para-amino-hippurate clearances, maximum tubular transport of para-aminohippurate, and renal acidification were within normal limits. In addition, renal concentrating and diluting abilities of these patients were similar to those of four normal controls. Urea clearances of both patients during maximum water diuresis (27.6 and 40.8 ml per minute per 1.73 m2) and antidiuresis (5.3 and 4.0), however, were much lower than mean (+/- S.E.M.) values in the normal controls (70.4 +/- 3.7 and 30.0 +/- 3.42 ml per minute per 1.73 m2, respectively). Thus decreased urea excretion despite otherwise normal renal function was responsible for the chronic azotemia of these patients. The genetic defect in renal urea clearance appeared to be inherited as an autosomal dominant trait.