Urea Reabsorption Research Articles

Changes in endogenous urea recycling and the handling of renal urea in pregnant and lactating Sardi sheep kept on a constant feeding level.

The kinetics of endogenous urea were compared during the last month of pregnancy, lactation, and a nonpregnant, nonlactating control period in Sardi sheep kept on a constant feed level. Urea entry rate estimated by injections of [14C]urea rose by 36% during pregnancy. Renal urea excretion was reduced by 40% during pregnancy and by 28% during lactation. Consequently, fractional urea recycling was greater during pregnancy and, to some extent, during lactation than during the control period. In a second series of experiments, glomerular filtration rate increased by 48% and urea filtration rate rose by 17% during pregnancy. During lactation, both glomerular filtration rate and urea filtration rate were close to control levels. It appears that the decreased renal urea excretion during pregnancy and lactation was due mainly to increased tubular reabsorption of urea. Rumination time increased by 15% during pregnancy. Rumen ammonia concentration was elevated in both pregnant and lactating ewes above the control period level. The results suggest that Sardi sheep possess a high potential for the conservation of nitrogen during pregnancy and lactation periods.

Urea flux in the ureter.

It has been hypothesized that urea from the final urine is recycled into the renal papilla through the pelvic epithelium. To test this hypothesis, samples of urine were collected by micropuncture proximally and distally through the intact, contracting ureter of the anesthetized rat. In 12 rats, in which urine flow was 5.89 +/- 0.67 microliter/min (a moderate antidiuresis), the ratio of proximal-to-distal urea concentration, corrected for water movement, was 0.93 +/- 0.03 (P less than 0.01 compared with unity), indicating that approximately 7% of urea in the urine emerging from the terminal collecting duct was reabsorbed by the time it reached the distal ureter. To assess the possible contribution of urea reabsorption by the ureter, the ureter was cannulated proximally and distally and perfused with urine of known composition at 6.26 +/- 0.10 microliter/min. In nine rats, the ratio of urea concentration in the perfusate collected from the distal end of the ureter to that in the perfusate entering the proximal end was 0.93 +/- 0.02 (P less than 0.01 compared with unity), indicating 7% reabsorption. Movement of solute across the ureteral epithelium was not restricted to urea. Potassium and creatinine were also reabsorbed [3.4 +/- 0.9 (P less than 0.01) and 3.5 +/- 1.2% (P less than 0.05), respectively], whereas sodium was secreted [9.2 +/- 2.3% (P less than 0.01)].(ABSTRACT TRUNCATED AT 250 WORDS)

Renal excretion of urea in a small east african antelope, the dik-dik ( Rhynchotragus kirkii)

1. 1. A study on the renal handling of urea by the dik-dik antelope ( Rhynchotragus kirkii) was conducted. 2. 2. Plasma and urine samples were analysed for osmolality, urea and creatinine concentrations during dehydration and intra-ruminal loading of potassium and sodium solutions. 3. 3. The glomerular nitration rate (GFR) of the dik-dik was found to be 182.6 ± 11.7 ml/min/100 kg body mass. 4. 4. Dehydration was observed to increase tubular urea reabsorption and increase plasma and urine osmolalities, but had no effect on the amount of urea filtered at the glomerulus. 5. 5. Potassium loading increased both GFR and urine flow rate.

Renal handling of urea in subjects with persistent azotemia and normal renal function

Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was normal and urea clearance was much lower than in 10 age-matched control subjects (23.3 +/- 2.1 ml/min and 49.6 +/- 2.6 ml/min per 1.73 m2, P less than 0.001). Inulin and para-aminohippurate clearances, blood volume and plasma concentration of antidiuretic hormone were within normal limits. During maximal antidiuresis, in spite of greater urea filtered load, the urinary excretion of urea was less, and both the maximum urinary osmolality and the free-water reabsorption relative to osmolar clearance per unit of GFR were greater than in control subjects. After sustained water diuresis, the plasma urea concentration markedly decreased to near normal levels in azotemic subjects. The basal urinary excretion of prostaglandins E2 was significantly reduced in azotemic subjects and was directly correlated with fractional urea clearance (r = 0.857, P less than 0.001). An additional group of control subjects (N = 8) showed a marked reduction of fractional clearance of urea after inhibition of prostaglandin synthesis (P less than 0.01). These data suggest that azotemia is due to increased tubular reabsorption of urea in the distal part of nephron, presumably because of increased back diffusion in the papillary collecting duct, accounting for the enhanced maximum urinary osmolality and free-water reabsorption. Renal prostaglandin E2 may participate in the pathogenesis of azotemia by altering recycling of urea in the medulla.

Renal architecture of the dogfish Scyliorhinus caniculus (Chondrichthyes, Elasmobranchii)

The excretory portion of the opisthonephric kidney of Scyliorhinus caniculus displays a mesial zone that is supplied with venous blood by the renal portal system and with arterial blood from the efferent arterioles of the glomeruli, and a zone of lateral bundles that is irrigated with arterial blood via arterioles in parallel to the afferent arterioles of the glomeruli. Each single nephron performs two large convolutions in the mesial tissue and two hairpin loops in the bundle. The nephron is differentiated into renal corpuscle (located between the two zones), neck segment (in the bundle), proximal segment I (beginning in the bundle, major convolution between the zones), proximal segment II (exclusively in the mesial zone), intermediate segment (beginning in the mesial tissue and ending in the bundle), distal segment (exclusively in the bundle) and collecting tubule (beginning in the bundle, with a large convolution in the mesial tissue and ending in the bundle) that joins the collecting duct-ureter system. In the bundles proximal and distal nephron segments, the end of the renal tubule and a central bundle vessel are arranged together and form a complex countercurrent system that is enclosed in a sheath of connective tissue. The bundles provide the structural basis for the creation of an environment with low urea concentration around the final portion of the renal tubules, which is consistent with previous experimental evidence of a significantly lower urea content of the bundles as compared with the blood and the mesial tissue in another marine elasmobranch, Raja erinacea. This condition is thought to lead to passive reabsorption of urea from the fluid of the end of the renal tubule. Separation of individual nephrons in the bundle zone appears to be correlated with the peculiar secondary structure that results from the folding of the bundles and may be in addition a requirement in conjunction with intermittent function of the glomeruli. The zonation of the renal tissue with formation of bundles with counter-current systems is characteristically found in marine Elasmobranchs and is considered to be the morphological correlate to the physiological ability of the marine Elasmobranchii to use urea for osmoregulation.

Exercise training-induced hypervolemia in the horse

The purpose of this study was to determine if a chronic hypervolemia would accompany endurance exercise training in the horse. Six mature previously inactive horses were utilized for this study. During the 5-wk experiment, five of the horses were trained for 14 d on a treadmill ergometer at a constant treadmill speed of 5.6 km X hr-1 and a constant grade of 12.5% for graduated lengths of time. One horse was trained by lunging at a trotting pace in a round pen. Following training, plasma volume increased by 4.7 1 (29.1%, P less than 0.05). Although the rate of daily water intake did not change during the training period, 24-h urine output decreased by an average of 3.5 1 X d-1 (-24.5%, P less than 0.05). Resting glomerular filtration rate and the rate of sodium clearance were not altered by training. However, urea, potassium, and osmotic clearance were decreased by training (P less than 0.05) while free water clearance was increased (P less than 0.05). Resting plasma aldosterone and arginine vasopressin concentrations were not altered by training. Plasma potassium concentration was significantly decreased (P less than 0.05) following the 2 wk of training. These data would appear to suggest that renal control mechanisms affecting water reabsorption via the re-absorption of urea and osmotically active substances other than sodium provide the primary route for the training-induced hypervolemia seen in horses.

Pathways of urea transport in the mammalian kidney

Urea is the chief end product of nitrogen metabolism in mammals. Most of the urea produced is excreted by the kidneys. Excretion of a large fraction of the urea filtered by the glomerulus is required to keep pace with the rate of hepatic urea production. Consequently, the maintenance of nitrogen balance depends on a sustained high rate of renal urea excretion. One factor that might challenge the ability of the kidney to maintain a high rate of urea excretion is the need to limit water excretion. Theoretically, an increase in water absorption along the nephron would be expected to increase luminal urea concentration and consequently increase the driving force for passive urea reabsorption. Indeed, as demonstrated originally by Shannon [1] and confirmed in many subsequent studies, the rate of urea excretion decreases when water excretion decreases. However, the decline in urea excretion is relatively modest, even when the rate of water excretion is very low. In Shannon's studies in dogs [1], when water diuresis was established (water excretion 5–10 percent of filtered load), urea excretion was about 60 percent of the filtered load. During antidiuresis, when water excretion was reduced by 95% or more (to less than 0.5 percent of the glomerular filtration rate), urea excretion fell only by 25 to 30% (to 40 to 45 percent of the filtered load).

Osmotic Diuresis

Osmotic diuresis occurs, if nonreabsorbed solutes such as mannitol impair the reabsorption of water. The reduced reabsorption of volume affects in turn the reabsorption and excretion of solutes. Thus, mannitol leads to modest impairment of proximal tubular reabsorption not only of water, but as well of electrolytes (Na, Cl, K, Pi, Ca, but not Mg), urea, and uric acid. Infusion of hypertonic mannitol increases renal blood flow and the glomerular filtration rate of superficial nephrons. The increased perfusion of medulla leads to wash out of medullary hypertonicity. The decline of medullary osmolarity leads to a marked impairment of water reabsorption in descending limbs and possibly to moderate impairment of NaCl, Ca, and Mg reabsorption in the ascending limbs of Henle's loop. In the collecting duct, inhibition is marked of water and urea reabsorption and modest of NaCl reabsorption. A number of open questions remain, such as the mechanisms underlying decrease of renal vascular resistance, increased proximal tubular reabsorption of magnesium, or impaired NaCl reabsorption in thick ascending limbs.

A mathematical model of the rat proximal tubule.

The equations of mass conservation and electroneutrality are used to extend a nonequilibrium thermodynamic model of the rat proximal tubule epithelium to a representation of a 0.5-cm segment of tubule. The output of the tubule model includes the luminal profiles and absolute proximal reabsorption of Na, K, Cl, HCO3, HPO4, H2PO4, glucose, and urea, generated by the epithelial model. Transport rates and permeabilities, chosen in agreement with those of the rat, result in luminal glucose and bicarbonate depletion and a transition from an electronegative to positive lumen. Despite the development of significant transepithelial osmotic driving forces (a transepithelial glucose gradient and Cl-HCO3 asymmetry), intraepithelial solute-solvent coupling remains an important force for water reabsorption along the proximal tubule length. In particular, this means that when osmotic gradients that appear under free-flow conditions are used in the calculation of the epithelial water permeability, a substantial overestimate of this permeability will be obtained. A single first-order differential equation has been derived in conjunction with an approximate nonelectrolyte model of the proximal tubule that represents both coupled and gradient-driven water reabsorption. In the present work, this equation is shown to yield an accurate description of water transport by the comprehensive tubule model.

Chemical and morphological differences in the kidney zones of the elasmobranch, Raja erinacea mitch

1. 1. The histological investigation of the kidney of the skate Raja erinacea revealed a thin cap of dorsal bundles, which contain segments of single nephrons that are arranged separately in a countercurrent manner, and a large ventral zone, where the second proximal segments (PII) and parts of the lower nephron are located. 2. 2. This zonation is apparent in fresh, unfixed material and makes it possible to separate small tissue samples under a dissecting microscope. 3. 3. The osmolality in both zones does not differ. 4. 4. The dorsal bundle zone had a lower urea concentration and a higher sodium concentration than the ventral zone. The differences in the mean concentrations of the tissue samples indicate a gradient for the two substances along the bundles. 5. 5. Determinations of amounts of water and solutes per mg solute-free, dry tissue of the two zones, showed that the amounts of water, total osmolytes, Na and K were greater in the bundle zone than in the ventral zone, while the amount of urea was identical in the two zones. 6. 6. This indicates that the lower urea concentration in the bundle zone is established through an accumulation of Na and water in the interstitium. 7. 7. The countercurrent arrangement of very early and late segments of single renal tubules supports the concept of passive reabsorption of urea in the kidney of the marine elasmobranch.

Role of mandibular striated duct in salivary excretion of urea in dogs.

The role of mandibular striated duct in salivary excretion of endogenous urea was studied by a technique of retrograde ductal injection of HgCl2 and a stop flow analysis. (1) It was verified in this study that treatment with HgCl2 markedly inhibited Na+ reabsorption in the striated duct so that water reabsorption driven by the Na+ reabsorption would be inhibited substantially. (2) The saliva/plasma concentration ratios (S/P ratios) of urea in HgCl2-treated saliva (about 0.71) were significantly higher than those in untreated saliva (about 0.37). (3) The excretion rate of urea in HgCl2-treated saliva (about 0.02 mg/min/kg) was also significantly higher than those in untreated saliva (about 0.01 mg/min/kg) despite the same flow rate for both saliva samples. Furthermore, (4) The S/P ratios of urea in the second (0.25-0.50 ml) poststop-flow saliva (about 0.65) were significantly higher than those in prestop-flow saliva (about 0.35). These results suggest a possibility that salivary urea is reabsorbed in the dog mandibular striated duct and that the enhancement of the S/P ratio as well as the salivary level of urea by the pre-treatment with HgCl2 may be due to the inhibition of urea reabsorption.

Urea reabsorption along the papillary collecting duct in potassium-deficient rats.

These experiments were designed to evaluate the hypothesis that K+ deficiency may be associated with decreased delivery of urea to the renal papillary collecting duct and/or decreased reabsorption of urea from the papillary collecting duct. Either of these factors would result in diminished capacity for urea recycling and might explain the mechanism of the urinary concentrating defect that is observed in K+ depletion. Munich-Wistar rats were fed 25 ml of water and 12 g of normal (CON) or K+-deficient (KD) diet each day for 21 days. Papillary collecting duct samples were obtained by micropuncture through the intact ureter. Fractional delivery of H2O to the base and tip of the papillary collecting duct was increased in KD as compared to CON rats (1.50 +/- 0.30% in KD vs 0.72 +/- 0.09% in CON at the base, P less than 0.01; and 0.55 +/- 0.08% in KD vs 0.30 +/- 0.05% in CON at the tip, P less than 0.01). However, fractional delivery of urea to the base and tip of the papillary collecting duct was not different between KD and CON rats (26.9 +/- 5.6% in KD vs 21.4 +/- 3.3% in CON at the base, P greater than 0.05; and 12.4 +/- 1.5% in KD vs 10.4 +/- 1.4% in CON at the tip, P greater than 0.05). Furthermore, reabsorption of water or urea between the base and tip of the papillary collecting duct was not decreased in KD as compared to CON rats (water reabsorption was 57.8 +/- 4.4% in KD and 55.9 +/- 5.11% in CON and urea reabsorption was 45.0 +/- 6.5% in KD and 45.9 +/- 5.4% in CON, P greater than 0.05). These results demonstrate that water reabsorption, but not urea reabsorption, is impaired in renal tubules proximal to the accessible papillary collecting duct in hydropenic rats.

Nitrogen metabolism and kidney function in the nubian ibex ( Capra ibex nubiana)

1. 1. The nitrogen economy of the Nubian ibex ( Capra ibex nubiana), a ruminant that inhabits harsh deserts, was studied in the laboratory when fed three diets of different quality. 2. 2. Even on the low quality roughage (wheat straw) the ibex was found capable of balancing its nitrogen economy. 3. 3. On feeds low in protein, recycling of urea played a major role in helping the ibex maintaining a balanced nitrogen metabolism. When on wheat straw, the ibex recycled 71.6% of the urea synthesized in its liver. 4. 4. When on feeds lower in protein, blood urea concentration dropped (from 11.4mM when on alfalfa hay to 3.2 mM when on wheat straw). GFR that amounted to 44.28 ml/min when on alfalfa hay decreased to 28.97ml/min when on wheat straw. 5. 5. Reabsorption of urea amounted to 48% of the urea filtered when on alfalfa hay and increased to 78.8% on wheat straw.

Renal control of plasma urea level in sheep: the diuretic effect of urea, potassium and sodium chloride.

Two merino ewes were fed 800 and then 1000 g of lucerne chaff per day and renal responses and extracellular fluid volume (E.C.F.) were determined. Urine urea nitrogen, glomerular filtration rate (G.F.R.), urine volume, effective renal plasma flow (E.R.P.F.) and E.C.F. increased in both animals with the greater nitrogen intake. In a second experiment, five merino wethers and four merino ewes were infused intraruminally with increasing quantities of urea, whilst being fed a mainly roughage ration, and the above parameters were determined. No significant changes in G.F.R., E.R.P.F. or E.C.F. were noted. Urinary excretion maintained a linear response to nitrogen input until 20.6 g of urea nitrogen per day were infused. At this level of infusion, an increased fractional reabsorption of urea resulted in a large increase in plasma urea concentration, but when 500 mmol of NaCl or KCl were added to the infusate, urine urea nitrogen excretion increased from 10.4 to 11.4 and 11.9 g/d respectively and plasma urea concentration decreased from 68.0 to 35.2 and 37.3 mg nitrogen/100 ml. Urea clearance virtually trebled with both electrolyte infusions and E.C.F. and G.F.R. increased by approximately 10 and 25% respectively. It is concluded that urea alone has limited diuretic ability and that the increased electrolyte content of higher protein dry roughage diets aids urine urea excretion by increasing G.F.R., and the urine flow rate by an osmotic diuretic effect.

The influence of cortisol excess on kidney function in the dog.

The effects of cortisol excess on kidney function were studied in 8 normal conscious dogs. Cortisol was given orally until polyuria developed. Cortisol excess decreased urine osmolality (from 897 +/- 76 to 186 +/- 36 mosm. kg-1) and increased urine production (from 0.7 +/- 0.1 to 9.3 +/- 2.4 ml kg-1. h-1). The glomerular filtration rate increased by 23 +/- 9 per cent. Sodium and potassium concentrations in plasma were decreased. 66 Per cent of the increase in urine production was due to the increase in free water clearance and 34 per cent to the increased urea excretion. Cortisol excess apparently caused polyuria by inhibition of the action of ADH in the collecting duct, resulting in a decreased water and urea reabsorption. The decreased urea reabsorption possibly causes a smaller urea recirculation in the renal medulla and hence a decrease in concentrating capacity.

Renal Function in the Spectacled Hare-Wallaby, Lagorchestes conspicillatus: Effects of Dehydration and Protein Deficiency

Renal function was studied in a marsupial, the spectacled hare-wallaby Lagorchestes conspicillatus, and the effects of acute dehydration and exposure to a low-protein diet assessed. The rate of glomerular filtration (GFR), measured as the inulin clearance, fell significantly with both treatments but tubular function was unaffected. This reduction in GFR accounted entirely for the antidiuresis observed with both dehydration and exposure to low-protein intake and accords with field observations of the hare- wallaby, where urine volumes are characteristically low and have low osmolalities. When data from animals on both high and low-protein diets were considered together, the clearance ratio for urea (C*urea/C*in) was found to be positively correlated with the rate of urine production, and it is evident that mechanisms which invoke antidiuresis in this species will automatically enhance the reabsorption of urea.

The influence of indomethacin on renal concentrating and diluting capacity in sickle cell nephropathy.

1. The effects of indomethacin on water excretion during both vasopressin stimulation and inhibition were studied in control subjects and in patients with sickle cell anaemia. 2. In the control group as well as in the group of patients with sickle cell anaemia sodium and urea retention occurred after indomethacin in the water-depleted state. During water loading, indomethacin induced sodium retention without urea reabsorption. 3. In healthy volunteers indomethacin increased urinary osmolality during water deprivation, but not after water loading. In contrast, in patients with sickle cell anaemia indomethacin caused a rise in urinary osmolality during water loading, but not after deprivation. 4. The findings support the view that indomethacin promotes solute reabsorption in the distal tubule. 5. From our observations we conclude that renal prostaglandins are not involved in the urinary concentrating defect of patients with sickle cell anaemia. On the other hand, the normal diluting capacity in sickle cell anaemia appears to depend on renal prostaglandins.

Urea reabsorption in the medullary collecting duct of protein-depleted young rats before and after urea infusion.

The aims of the present study were to examine urea handling along the length of the medullary collecting duct (MCD) in protein-depleted young rats and to determine the effect of urea infusion on MCD function and urine concentrating ability. In 10 young rats on a low protein diet, urea reabsorption equivalent to 18.3% of the filtered load was observed along the MCD (4.5 mm) using the microcatheterization technique. Collecting duct urea reabsorption occurred almost entirely (16.6%) in the distal portion of the MCD (mid-zone to papillary tip, 2.8 mm). These results are in contrast to the lack of net urea reabsorption along the MCD in protein-replete adult rats [21]. After urea infusion which raised plasma urea level from 3.5 to 10.5 mmol/l in protein-depleted rats, urine non-urea solute concentration increased in the non-exposed right kidney from 827 to 1,199 mosm kg−1 (P<0.001) but the increase was not significant in the experimental left kidney (590 to 619 mosm kg−1). Thus exposure of the papilla interfered with urea-induced enhancement of urine concentrating ability. After urea infusion, fractional urea reabsorption in the distal portion of the MCD was similar to that before infusion (21.1%) of filtered load) but the absolute load of urea delivered to the MCD and reabsorbed along the duct was markedly increased (2.7-fold). In 6 rats with an increase in urine non-urea solute concentration in the experimental kidney after urea infusion, fluid reabsorption along the duct was significantly increased. The results indicate that in protein-depleted young rats (1) there is significant urea reabsorption in the distal portion of the medullary collecting duct, (2) urea infusion contributes to enhanced urine concentrating ability, in part, by increasing absolute urea reabsorption and also water reabsorption in the collecting duct.

Renal Urea Handling in Goats Fed High and Low Protein Diets

Four female goats first were fed a high protein diet and later a low protein diet. Renal urea handling was studied during feeding of both diets. Glomerular filtration rate was measured with [hydroxymethyl-carbon-14]inulin. Glomerular filtration rate dropped about 60% when nitrogen intake was restricted. Urea concentration of plasma fell from 6mM on high protein diet to .6mM on low protein diet. On low protein diet the rate of urea filtration at the glomeruli was only 4% of that on high protein diet, 22 versus 519μmol/min. In addition, tubular urea reabsorption in percentage of filtered urea rose up to 92% on low protein diet. As a result of all these renal changes following dietary nitrogen restriction, urinary urea excretion was only .6% of urinary urea excretion on high protein diet. In goats as in other ruminants, renal mechanisms effectively contribute to urea conservation during protein deprivation.

Mathematical model of mass transport throughout the kidney: Effects of nephron heterogeneity and tubular-vascular organization

A model of transport processes throughout the mammalian kidney is presented. Structural features of the model include labyrinth and medullary ray subsystems in the cortex, distinct vasa recta and capillary plexus subsystems in the outer and inner stripes, and an inner zone subsystem. Distinctions are also made between short and long nephrons, juxtamedullary and nonjuxtamedullary nephrons, vasculature, and interstitial spaces. Salt, urea, plasma proteins, and miscellaneous “nonreabsorbable” solutes in tubular and interstitial fluids are chosen as the essential solutes for describing renal mass transport. Geometric and number density data of vessels are taken from anatomical studies. Membrane parameters are evaluated principally from isolated rabbit tubule perfusion and rat micropuncture experiments. By numerical solution of the mass transport equations, the mild antidiuretic, steady state of a rat is simulated. To assess the importance of special structual features of the model, simulations were performed with different values of the anatomical parameters. By distributing more arterial blood toward the inner cortex and medulla, the osmotic gradient in the inner stripe is reduced while the urinary water and solute excretion rates are increased. When the reabsorption of urea from the papillary collecting duct is enhanced, the interstitial osmotic gradient monotonically increases throughout the inner medulla.