Fractional Free Water Reabsorption Research Articles

Renal tubular sensitivity to atrial natriuretic factor in essential hypertension

To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension. Nine healthy volunteers and six patients with essential hypertension were studied on four test days under standard conditions, water loading and hydropenia with mannitol or saline loading. On each test day baseline, atrial natriuretic factor infusion (1 microgram/min) and recovery measurements were performed after equilibrium had been reached. The measurements included the atrial natriuretic factor (ANF) plasma levels, blood pressure, glomerular filtration rate (GFR), effective renal plasma flow, urinary osmolality and the (fractional) excretions of (free) water, sodium and potassium. Fractional free-water excretion and free-water reabsorption (as a function of osmolar clearance) were calculated during water loading and hydropenia with mannitol or saline loading, respectively, using standard formulae. [125I]-iothalamate and [131I]-hippuran were infused continuously for the measurement of GFR and effective renal plasma flow, respectively. The plasma ANF concentration rose five- to eightfold during the infusion of ANF, which induced an increase in urinary sodium excretion, a small increase in GFR and a decrease in the effective renal plasma flow. Moreover, ANF induced an increase in fractional free-water excretion and a decrease in fractional free-water reabsorption. These changes did not correlate with changes in GFR. The blood pressure and potassium excretion were not affected. The effects of ANF on the plasma ANF levels, natriuresis and renal haemodynamics did not differ between the normotensive and the essential hypertensives. However, the increase in fractional free-water excretion was significantly greater in the patients with essential hypertension and correlated significantly with blood pressure (r = 0.56, P < 0.05). These results indicate that the infusion of ANF at a low dose induces a similar natriuretic response in normotensive subjects and in patients with essential hypertension. This natriuresis is probably the result of both a glomerular and a tubular effect of ANF. Proximal as well as distal tubular sites seem to be involved. In essential hypertension an enhanced proximal as well as an impaired distal tubular action of ANF can be hypothesized.

Effect of high-protein diet on renal concentration capacity in rabbits

In the present studies, we have found that New Zealand White rabbits kept on normal rabbit chow (16% protein, LP) are unable to raise fractional free water reabsorption [TCH2O divided by glomerular filtration rate (GFR)] as the fractional osmotic load (Cosm/GFR) is increased. Acute administration of urea (400 mosmol/l) or indomethacin (10 mg/kg iv bolus, followed by 0.25 mg/min infusion) corrects the defect. Moreover, rabbits kept for 2 wk on a 40% protein diet (HP) showed marked improvement in their renal concentration capacity. Balance studies showed that, in rabbits on HP, urine prostaglandin E2 (PGE2) excretion was lower while GFR, urine urea, and osmolar excretion were significantly higher than in rabbits in the LP group. Medullary tissue electrolytes in the HP vs. LP group were as follows: urea, 1,035 +/- 90 vs. 790 +/- 60 mmol.l-1 x g wet tissue wt-1; tissue Na+, 548 +/- 96 vs. 298 +/- 37 meq.l-1 x g wet wt-1; and K+, 201 +/- 43 vs. 99 +/- 16 meq.l-1 x g wet wt-1. Also, medullary slices from animals on HP had a lower PGE2 synthesis than those on LP when stimulated with angiotensin II (ANG II). Papillary plasma flow (PPF) measured by the accumulation of 125I-labeled albumin, after infusion of vasopressin, was 13.7 +/- 2.0 in the HP group and 22.7 +/- 3.4 ml.min-1 x 100 g-1 in the LP group. These findings suggest that lower PPF and higher urea and electrolyte content in the medullary interstitium of HP intake results from inability to produce medullary PGE2 even during ANG II or antidiuretic hormone (ADH) stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute effects on furosemide and mannitol on renal function in the early postoperative period.

The effects of furosemide and mannitol on renal function in the immediate postoperative period were studied in 16 patients, who had undergone upper abdominal surgery under neurolept anaesthesia. Renal function was studied preoperatively and during the first postoperative hour with a standard clearance technique. The patients were then randomly given furosemide, 1 mg/kg b.w., or mannitol, 0.5 g/kg b.w. Renal function was further investigated during the following 6 h in periods of varying duration. The injection of furosemide caused an initial increase of renal plasma flow (RPF), while glomerular filtration rate (GFR) decreased. Striking increases of urine flow, fractional sodium, fractional chloride and fractional osmolal excretion were found. These increases reached maximum levels during the second 20‐min clearance period after the injection. Fractional free water reabsorption decreased and during the first 20‐min clearance period it changed into free water clearance. These changes had reached or nearly reached the preoperative control levels after 6 h.The infusion of mannitol caused an initial rise in RPF, while GFR remained stable. Increases were found in urine flow, fractional sodium, fractional chloride, fractional osmolal excretions and fractional free water reabsorption. The changes reached maximum levels during the first 20‐min control period and then gradually returned to the preoperative control levels.Mannitol did not impair GFR and had a milder effect on renal function than furosemide. The losses of sodium and water were much smaller in the mannitol group than in the furosemide group. It is therefore concluded that mannitol should be used as the diuretic of choice in the treatment of postoperative oliguria in patients without known cardiovascular disease associated with increased preload and/or left ventricular insufficiency.

Renal function during neurolept anaesthesia.

Renal function and central haemodynamics were studied in eight patients, without known histories of renal or cardiovascular disease, during and immediately after upper abdominal surgery under neurolept anaesthesia. Inulin and PAH clearance, fractional sodium and fractional osmolar excretion decreased, while fractional free water reabsorption increased under anaesthesia. Cardiac output, mean systemic arterial pressure and systemic vascular resistance remained virtually unchanged both per- and postoperatively. Renal haemodynamics were promptly restored postoperatively, while fractional sodium and fractional osmolal excretion were unaltered and antidiuresis increased. It is concluded that neurolept anaesthesia, as far as renal function is concerned, is well suited for the anaesthetic management of the poor-risk patient.

Diuretic activity in human urine: lack of action on proximal tubule and frog skin sodium transport.

We previously described a high molecular weight fraction of human urine that causes diuresis and natriuresis in sodium depleted rats. In the present study the site of action of this fraction was investigated in hydropenic rats using micropuncture. I.v. injection of 100 µg/kg body weight of the urine extract caused a significant increase in both urinary sodium and water excretion. The rise in urinary sodium excretion wasdue mainly to a rise in water excretion. Negative free water clearance (TcH2O) decreased significantly following injection of the extract. No change in late proximal and early distal TF/P inulin and TF/P Na+ was observed indicating that fractional sodium and water reabsorption by the proximal tubule and the loop of Henle were not influenced by the extract. Total GFR, and superficial single nephron GFR remained constant. In a second study the urine extract was tested for effects on Na+ transport by frog skin. Potential difference and short circuit current were not affected by the extract even after separating the epithelium from the corium by use of collagenase. The data suggest that the extract has no direct inhibitory effect on Na+ transport by rat surface tubules and frog skin. The diuresis may be explained by a decrease in fractional free water reabsorption presumably caused by an increase in medullary blood flow.

The postobstructive kidney. Observations on nephron function after the relief of 24 hr of ureteral ligation in the dog.

After the relief of 24 hr of complete unilateral ureteral obstruction in the dog, the experimental kidney is characterized by a decrease in filtration rate and an increase in fractional and often absolute excretion of sodium before and after the administration of mannitol. In the hydrated state, the failure to conserve sodium is associated with increases in fractional free water clearance and fractional sodium supply to water-freeing sites signifying that the augmented sodium excretion is derived from a proximal source. In the hydropenic state there is decreased fractional free water reabsorption, and sometimes free water excretion, in the postobstructive kidney. An early plateau in free water reabsorption is associated with an increased fractional excretion of sodium. These findings are attributed to the early development of distal nephron impermeability to water as a result of enhanced distal tubular supply and transport of sodium. There is a decrease in maximal tubular reabsorptive capacity (Tm) of glucose in the post-obstructive kidney which is, however, less marked than the decrease in filtration rate. The fall in filtration rate is to some extent likely due to a dropping out of nephrons from the circulation while the remaining nephrons are hypoperfused. The magnitude of the sodium reabsorptive defect is markedly exaggerated as the concentration of nonreabsorbable solute (mannitol) in the glomerular perfusate is increased. It is concluded that the postobstructive increase in sodium excretion during mannitol administration is in part due to a limit in the capacity to reabsorb sodium against a concentration gradient in the proximal tubule.