scholarly journals Is the process of urinary urea concentration responsible for a high glomerular filtration rate?

1993 ◽  
Vol 4 (5) ◽  
pp. 1091-1103
Author(s):  
L Bankir ◽  
M Ahloulay ◽  
N Bouby ◽  
M M Trinh-Trang-Tan ◽  
F Machet ◽  
...  
Keyword(s):  
Tubuloglomerular Feedback ◽  
Sodium Reabsorption ◽  
Urinary Concentration ◽  
Urinary Flow ◽  
Moderate Increase ◽  
Thick Ascending Limb ◽  
High Concentration ◽  
Plasma Urea ◽  
Urea Excretion ◽  
Urea Reabsorption

For subjects on a normal diet, urea is the major urinary solute and is markedly concentrated in the urine compared with in the plasma. Because urea is not known to undergo active secretion, its excretion rests on filtration lessened to a variable extent by tubular reabsorption. It is well established that the efficiency of urea excretion drops with increasing urinary concentration and decreasing urinary flow rate (from approximately 60% of filtered load, above 2 mL/min, to approximately 20% below 0.5 mL/min) because the prolonged transit time in the distal nephron favors passive urea reabsorption. Thus, a higher urinary concentration is achieved at the expense of a reduced efficiency of urea excretion. Recent experimental observations suggest that GFR could actually increase in parallel with the urinary concentrating activity, thus ensuring a normal urea excretion in the face of a high, concentration-dependent urea reabsorption, with only a moderate increase in plasma urea. A possible mechanism is proposed that could explain how the vasopressin-induced intrarenal recycling of urea (which contributes to improvement in urinary concentration), but not an exogenous urea administration, could indirectly depress the tubuloglomerular feedback and hence increase GFR. An increased concentration of an osmotically active solute in the thick ascending limb of Henle's loop (such as urea and, in some cases, glucose) could enable a lower NaCl concentration to be achieved at the macula densa by reducing the osmotically driven water leakage in this nephron segment. This mechanism could explain the hyperfiltration seen in various pathophysiologic situations such as chronic vasopressin infusion, high protein intake, severe burns, and diabetes mellitus. Whatever the mechanism, if the need to excrete relatively high amounts of urea in a concentrated urine leads to a sustained elevation of GFR, the price to pay for this water economy is higher than generally assumed. It is not limited to the energy spent in the sodium reabsorption providing the "single effect" for the urinary concentrating process. It also includes the consequences on the glomerular filter of sustained high pressure and flow and the energy spent in reabsorbing the extra load of solutes filtered. In chronic renal failure, the ability to form hypertonic urine declines but is nevertheless well preserved with respect to declining GFR, thus imposing on remnant nephrons an additional permanent stimulus for hyperfiltration.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract 36: Deficiency in the Production of 20-HETE Contributes to Impaired Myogenic and TGF Responses in the Afferent Arteriole of Dahl S Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Ying Ge ◽  
Fan Fan ◽  
Sydney R Murphy ◽  
Jan Michael Williams ◽  
Ruisheng Liu ◽  
...  
Keyword(s):  
Renal Injury ◽  
Tubuloglomerular Feedback ◽  
Brown Norway ◽  
Sodium Reabsorption ◽  
Thick Ascending Limb ◽  
Afferent Arteriole ◽  
Synthesis Inhibitor ◽  
Renal Vasculature ◽  
Luminal Diameter ◽  
Consomic Strain

Previous studies have indicated that a deficiency in the formation of 20-HETE in the proximal tubule and thick ascending limb of Henle in Dahl S rats increases sodium reabsorption and contributes to the development of hypertension. The present study examined whether the lack of 20-HETE production in the renal vasculature contributes to the progression of renal injury by altering the myogenic or tubuloglomerular feedback (TGF) response of the afferent arteriole (Af-Art). The production of 20-HETE was significantly lower by 54% in renal microvessels isolated from the kidneys of Dahl S rats versus that seen than in SS.5BN consomic strain in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes responsible for the formation of 20-HETE was transferred into the Dahl S genetic background. The luminal diameter of the Af-Art decreased by 14.7± 1.5% (from 20.5 ± 0.7 to 17.5 ± 0.8 μm, n=6) in SS.5BN rats whereas the diameter of the Af-Art remained unaltered in Dahl S rats (from 20.1 ± 0.6 to 21.7 ± 0.6 μm, n=7) when the perfusion pressure was increased from 60 mmHg to 120 mmHg. In other experiments, adenosine (1 μM) reduced the diameter of the Af-Art in the SS.5BN rats by 15±0.7% (from 20.1 ±0.4 to 17.1 ± 0.9 μm, n=3) whereas the Af-Art of Dahl S rats was unaltered. However, administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM, n=6), or a selective 20-HETE antagonist, 6, 15-20-HEDE (10 μM, n=6) completely blocked the myogenic and adenosine responses in the Af-Art of SS.5BN rats but it had no effect in Dahl S rats. Administration of a 20-HETE agonist, 5, 14-20-HEDE (1 μM) restored the myogenic response (from 20.7 ± 0.7 to 17.6 ± 0.6 μm, n=7) and vasoconstrictor response to adenosine in the Af-Art of Dahl S rats. These studies confirm the key role of 20-HETE in modulating the responsiveness of the Af-Art and indicate that a deficiency in the formation of 20-HETE in renal microvessels contributes to the marked susceptibility of Dahl S rats to develop hypertension induced renal injury.

scholarly journals Renal responses of reindeer to high and low protein diet and sodium supplement

1979 ◽  
Vol 51 (1) ◽  
pp. 381-419 ◽  
Author(s):  
Maija Valtonen
Keyword(s):  
Sodium Chloride ◽  
Urine Osmolality ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Plasma Urea ◽  
Urea Excretion ◽  
Low Protein ◽  
Urea Reabsorption ◽  
Solute Excretion ◽  
Sodium Chloride Intake

The effects of reducing dietary nitrogen and increasing sodium chloride intake on renal function were studied in reindeer in order so elucidate the extent of urea conservation and solute excretion by the reindeer kidney. The fall in plasma urea concentration and urea excretion on the low protein diet was accompanied by a significant reduction in the glomerular filtration rate (GFR) and urine osmolality. The fraction of filtered urea reabsorbed increased. However, the contribution of the fall of the GFR to restriction of urinary losses of urea was far more significant than the increase in fractional urea reabsorption. The increase in sodium chloride intake reflected in icreased urinary sodium excretion, inducing a rise in urine osmolality on the low protein diet. Increased excretion of sodium was accompanied by decreased urea excretion. This interdependence of urea and sodium in urine excretion was particularly pronounced during the mating season in the autumn, when prominent retention of electrolytes and water was observed. On low protein diet, when reindeer were exposed to cold, the energy intake proved insufficient. The use of body protein as energy source resulted in increased plasma urea values. The fractional reabsorption of urea decreased, but the GFR stayed low. The GFR seems to be unaffected by plasma urea concentrations but is in some way regulated by the intake of dietary protein. Also on lichen diet the intake was not sufficient to satisfy the energy requirements and the plasma urea concentrations increased. The urea excretion was still low due to a decreased GFR. The high moisture content of lichen caused an increase in the urine water excretion, but no increase occured in the solute excretion. The rumen ammonia concentrations correlated significantly with the plasma urea concentrations, showing that urea is readily returned to the rumen in reindeer. The restriction of urea excretion on low protein intake contributes to the nitrogen economy and in reindeer it is brought about by a marked decrease in the GFR together with an increase in the urea reabsorption.

Protein- and diabetes-induced glomerular hyperfiltration: role of glucagon, vasopressin, and urea

2015 ◽  
Vol 309 (1) ◽  
pp. F2-F23 ◽  
Author(s):  
Lise Bankir ◽  
Ronan Roussel ◽  
Nadine Bouby
Keyword(s):  
Amino Acids ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Urea Synthesis ◽  
Paracrine Factors ◽  
Urea Excretion ◽  
Terrestrial Mammals ◽  
Water Economy ◽  
End Products ◽  
Set Up

A single protein-rich meal (or an infusion of amino acids) is known to increase the glomerular filtration rate (GFR) for a few hours, a phenomenon known as “hyperfiltration.” It is important to understand the factors that initiate this upregulation because it becomes maladaptive in the long term. Several mediators and paracrine factors have been shown to participate in this upregulation, but they are not directly triggered by protein intake. Here, we explain how a rise in glucagon and in vasopressin secretion, directly induced by protein ingestion, might be the initial factors triggering the hepatic and renal events leading to an increase in the GFR. Their effects include metabolic actions in the liver and stimulation of sodium chloride reabsorption in the thick ascending limb. Glucagon is not only a glucoregulatory hormone. It is also important for the excretion of nitrogen end products by stimulating both urea synthesis in the liver (along with gluconeogenesis from amino acids) and urea excretion by the kidney. Vasopressin allows the concentration of nitrogenous end products (urea, ammonia, etc.) and other protein-associated wastes in a hyperosmotic urine, thus allowing a very significant water economy characteristic of all terrestrial mammals. No hyperfiltration occurs in the absence of one or the other hormone. Experimental results suggest that the combined actions of these two hormones, along with the complex intrarenal handling of urea, lead to alter the composition of the tubular fluid at the macula densa and to reduce the intensity of the signal activating the tubuloglomerular feedback control of GFR, thus allowing GFR to raise. Altogether, glucagon, vasopressin, and urea contribute to set up the best compromise between efficient urea excretion and water economy.

Nonlinear filter properties of the thick ascending limb

1997 ◽  
Vol 273 (4) ◽  
pp. F625-F634 ◽  
Author(s):  
H. E. Layton ◽  
E. Bruce Pitman ◽  
Leon C. Moore
Keyword(s):  
Steady State ◽  
Frequency Response ◽  
Transit Time ◽  
Concentration Profile ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Transport Parameters ◽  
Nodal Structure ◽  
Nacl Concentration ◽  
Fluid Transit Time

A mathematical model was used to investigate the filter properties of the thick ascending limb (TAL), that is, the response of TAL luminal NaCl concentration to oscillations in tubular fluid flow. For the special case of no transtubular NaCl backleak and for spatially homogeneous transport parameters, the model predicts that NaCl concentration in intratubular fluid at each location along the TAL depends only on the fluid transit time up the TAL to that location. This exact mathematical result has four important consequences: 1) when a sinusoidal component is added to steady-state TAL flow, the NaCl concentration at the macula densa (MD) undergoes oscillations that are bounded by a range interval envelope with magnitude that decreases as a function of oscillatory frequency; 2) the frequency response within the range envelope exhibits nodes at those frequencies where the oscillatory flow has a transit time to the MD that equals the steady-state fluid transit time (this nodal structure arises from the establishment of standing waves in luminal concentration, relative to the steady-state concentration profile, along the length of the TAL); 3) for any dynamically changing but positive TAL flow rate, the luminal TAL NaCl concentration profile along the TAL decreases monotonically as a function of TAL length; and 4) sinusoidal oscillations in TAL flow, except at nodal frequencies, result in nonsinusoidal oscillations in NaCl concentration at the MD. Numerical calculations that include NaCl backleak exhibit solutions with these same four properties. For parameters in the physiological range, the first few nodes in the frequency response curve are separated by antinodes of significant amplitude, and the nodes arise at frequencies well below the frequency of respiration in rat. Therefore, the nodal structure and nonsinusoidal oscillations should be detectable in experiments, and they may influence the dynamic behavior of the tubuloglomerular feedback system.

Natriuresis in Rats Acutely Depleted of Chloride

1977 ◽  
Vol 52 (1) ◽  
pp. 23-31
Author(s):  
R. G. Luke ◽  
B. T. Khanh ◽  
R. D. Schmidt ◽  
J. H. Galla
Keyword(s):  
Sodium Bicarbonate Solution ◽  
Free Water ◽  
Sodium Reabsorption ◽  
Urinary Flow ◽  
Variable Degree ◽  
Water Reabsorption ◽  
Chloride Depletion ◽  
Sodium Load ◽  
Clearance Studies ◽  
And Control

1. Acute chloride depletion, without sodium depletion, was produced in rats by a single exchange peritoneal dialysis against sodium bicarbonate solution. Blood volume was restored after dialysis by infusion of salt-free albumin, and exogenous deoxycorticosterone and antidiuretic hormone were given. 2. Clearance studies in the period (3 h) after dialysis revealed no difference in the glomerular filtration rate or in the filtered sodium load between experimental and control rats but urinary sodium concentrations and absolute and fractional sodium excretion were significantly higher in the chloride-depleted group. 3. There was also a significant kaliuresis, increased urinary flow rate and diminished free water reabsorption. Urinary bicarbonate excretion increased to a variable degree but the major rise in anion excretion was ‘unmeasured’ (Na+ + K+ — [Cl− +HCO3− +PO43-]). 4. It is postulated that chloride depletion imposes limitations on sodium reabsorption in the ascending limb of the loop of Henle.

In Reply: Pathogenesis of Hyposthenuria in Sickle Cell Anemia

PEDIATRICS ◽  
1960 ◽  
Vol 26 (6) ◽  
pp. 1051-1052
Author(s):  
Hans G. Keitel
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Normal Level ◽  
Urinary Concentration ◽  
Urea Excretion ◽  
Low Level ◽  
Concentration Of Urine

In reply to the question raised by Dr. Morgan, it is now well established that urea plays an important part in the concentration of urine. Starting at a very low level of urea excretion, the urinary concentration maxima (as obtained during prolonged fluid deprivation, or following sustained vasopressin stimulation) is less than normal. When the rate of urea excretion is increased to the normal level, the maximal urinary concentration ability increases, but when the rate of urea excreted increases markedly, the urinary concentration maxima once again decreases.

Stimulation of renal sodium reabsorption by angiotensin II

1977 ◽  
Vol 232 (4) ◽  
pp. F298-F306 ◽  
Author(s):  
M. D. Johnson ◽  
R. L. Malvin
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Flow Rate ◽  
Sodium Reabsorption ◽  
Urinary Flow ◽  
Filtration Fraction ◽  
Water Diuresis ◽  
Urinary Osmolality ◽  
Anesthetized Dogs ◽  
Renal Sodium Reabsorption

Various parameters of renal function were studied before, during, and after the infusion of physiological increments of angiotensin II directly into one renal artery of anesthetized dogs. During water diuresis and during antidiuresis induced with exogenous antidiuretic hormone (ADH), angiotensin II consistently reduced UNaV, UKV, and CPAH, and increased the filtration fraction in the infused kidney. Urinary osmolality was increased only in the presence of ADH, while during water diuresis angiotensin II had no apparent effect on urinary osmolality or flow rate. During saline diuresis, a mean increment of angiotensin II concentration of 14 pg/ml was sufficient to significantly reduce UNaV and urinary flow rate. Changes in CCr, CPAH, and filtration fraction did not correlate with changes in sodium excretion, and intracortical distribution of blood flow remained unaltered. These data support the hypothesis that normal circulating levels of angiogensin II play a direct renal role in the control of sodium, potassium, and water homeostasis, and that angiotensin II exerts a direct, stimulatory effect on tubular sodium reabsorption independent of changes in GFR, RPF, filtration fraction, or intracortical distribution of blood flow.

Micropuncture analysis of single-nephron function in NHE3-deficient mice

1999 ◽  
Vol 277 (3) ◽  
pp. F447-F453 ◽  
Author(s):  
John N. Lorenz ◽  
Patrick J. Schultheis ◽  
Timothy Traynor ◽  
Gary E. Shull ◽  
Jürgen Schnermann
Keyword(s):  
Proximal Tubule ◽  
Filtration Rate ◽  
Distal Tubule ◽  
Transport Processes ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Fluid Reabsorption ◽  
Fluid Delivery ◽  
Single Nephron ◽  
Flow Pressure

The Na/H exchanger isoform 3 (NHE3) is expressed in the proximal tubule and thick ascending limb and contributes to the reabsorption of fluid and electrolytes in these segments. The contribution of NHE3 to fluid reabsorption was assessed by micropuncture in homozygous ( Nhe3 −/−) and heterozygous ( Nhe3 +/−) knockout mice, and in their wild-type (WT, Nhe3 +/+) littermates. Arterial pressure was lower in the Nhe3 −/−mice (89 ± 6 mmHg) compared with Nhe3 +/+ (118 ± 4) and Nhe3 +/−(108 ± 5). Collections from proximal and distal tubules demonstrated that proximal fluid reabsorption was blunted in both Nhe3 +/− and Nhe3 −/−mice (WT, 4.2 ± 0.3; Nhe3 +/−, 3.4 ± 0.2; and Nhe3 −/−, 2.6 ± 0.3 nl/min; P < 0.05). However, distal delivery of fluid was not different among the three groups of mice (WT, 3.3 ± 0.4 nl/min; Nhe3 +/−, 3.3 ± 0.2 nl/min; and Nhe3 −/−, 3.0 ± 0.4 nl/min; P < 0.05). In Nhe3 −/−mice, this compensation was largely attributable to decreased single-nephron glomerular filtration rate (SNGFR): 10.7 ± 0.9 nl/min in the Nhe3 +/+ vs. 6.6 ± 0.8 nl/min in the Nhe3 −/−, measured distally. Proximal-distal SNGFR differences in Nhe3 −/−mice indicated that much of the decrease in SNGFR was due to activation of tubuloglomerular feedback (TGF), and measurements of stop-flow pressure confirmed that TGF is intact in Nhe3 −/−animals. In contrast to Nhe3 −/−mice, normalization of early distal flow rate in Nhe3 +/−mice was not related to decreased SNGFR (9.9 ± 0.7 nl/min), but rather, to increased fluid reabsorption in the loop segment ( Nhe3 +/+, 2.6 ± 0.2; Nhe3 +/−, 3.6 ± 0.5 nl/min). We conclude that NHE3 is a major Na/H exchanger isoform mediating Na+ and fluid reabsorption in the proximal tubule. In animals with NHE3 deficiency, normalization of fluid delivery to the distal tubule is achieved through alterations in filtration rate and/or downstream transport processes.

Urea Excretion in the Camel

1957 ◽  
Vol 188 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Bodil Schmidt-Nielsen ◽  
Knut Schmidt-Nielsen ◽  
T. R. Houpt ◽  
S. A. Jarnum
Keyword(s):  
Glomerular Filtration Rate ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Urea Concentration ◽  
Nitrogen Excretion ◽  
Renal Tubules ◽  
Urea Clearance ◽  
Plasma Urea ◽  
Urea Excretion ◽  
Plasma Urea Concentration

The nitrogen excretion was studied in the one-humped camel, Camelus dromedarius. When a growing camel was maintained on a low N intake (dates and hay) the amount of N excreted in the form of urea, NH3 and creatinine decreased to 2–3 gm/day. This decrease was caused by a drop in urea excretion from 13 gm to 0.2–0.5 gm/day. Urea given intravenously during low N intake was not excreted but was retained. (The camel like other ruminants can utilize urea for microbial synthesis of protein.) The renal mechanism for urea excretion was investigated by measuring urea clearance and glomerular filtration rate during a period of 7 months. During normal N intake about 40% of the urea filtered in the glomeruli were excreted in the urine while during low N intake only 1–2% were excreted. The variations in urea clearance were independent of the plasma urea concentration and of glomerular filtration rate, but were related to N intake and rate of growth. No evidence of active tubular reabsorption of urea was found since the urine urea concentration at all times remained higher than the simultaneous plasma urea concentration. The findings are not in agreement with the current concept for the mechanism of urea excretion in mammals. It is concluded that the renal tubules must either vary their permeability to urea in a highly selective manner or secrete urea actively.

Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase

2007 ◽  
Vol 292 (6) ◽  
pp. F1867-F1872 ◽  
Author(s):  
Ruisheng Liu ◽  
Jeffrey L. Garvin ◽  
YiLin Ren ◽  
Patrick J. Pagano ◽  
Oscar A. Carretero
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Oxidase Inhibitor ◽  
Fluorescent Dye ◽  
Macula Densa ◽  
Superoxide Production ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Nacl Concentration

Superoxide (O2−) enhances tubuloglomerular feedback by scavenging nitric oxide at the macula densa. However, the singling pathway of O2− production in the macula densa is not known. We hypothesized that the increase in tubular NaCl concentration that initiates tubuloglomerular feedback induces O2− production by the macula densa via NAD(P)H oxidase, which is activated by macula densa depolarization. We isolated and microperfused the thick ascending limb of the loop of Henle and attached macula densa in rabbits. A fluorescent dye, dihydroethidium, was used to detect O2− production at the macula densa. When luminal NaCl was switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, O2− production significantly increased. To make sure that the shifts in the oxyethidium/dihydroethidium ratio were due to changes in O2−, we used tempol (10−4 M), a stable membrane-permeant superoxide dismutase mimetic. With tempol present, when we switched from 10 to 80 mM NaCl, the increase in oxyethidium/dihydroethidium ratio was blocked. To determine the source of O2−, we used the NAD(P)H oxidase inhibitor apocynin. When luminal NaCl was switched from 10 to 80 mM in the presence of apocynin, O2− production was inhibited by 80%. To see whether the effect of increasing luminal NaCl involves Na-K-2Cl cotransporters, we inhibited them with furosemide. When luminal NaCl was switched from 10 to 80 mM in the presence of furosemide, O2− production was blocked. To test whether depolarization of the macula densa induces O2− production, we artificially induced depolarization by adding valinomycin (10−6 M) and 25 mM KCl to the luminal perfusate. Depolarization alone significantly increases O2− production. We conclude that increasing luminal NaCl induces O2− production during tubuloglomerular feedback. O2− generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization.

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