Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance

Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldosterone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 +/- 0.11 vs. 1.29 +/- 0.12%, P less than 0.001; 12529 +/- 677 vs. 15707 +/- 796 microEq min-1 1.73 m-2 BSA, P less than 0.005; 2384 +/- 135.2 vs. 3685 +/- 219.3 microEq min-1 1.73 m-2 BSA, P less than 0.001; 19.5 +/- 1.0 vs. 24.2 +/- 1.3%, P less than 0.01; 2299 +/- 127 vs. 3485 +/- 214 microEq min-1 1.73 m-2 BSA, P less than 0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients (r = 0.62; P less than 0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 +/- 1.0 vs. 22.4 +/- 1.2%, P less than 0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 +/- 0.4 vs. 94.4 +/- 0.5%, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal water and sodium handling in compensated liver cirrhosis: mechanism of the impaired natriuresis after saline loading

The present study was attempted to evaluate sodium and water balance in compensated liver cirrhosis. Renal sodium and water handling was studied in six cirrhotic patients without ascites and/or oedema and in six controls before and after saline loading. Fractional sodium reabsorption at the various nephron sites (proximal, diluting and distal) was evaluated by means of clearance techniques during maximal water diuresis and hypotonic saline infusion. Compensated cirrhotic patients showed a normal baseline sodium and water balance but a blunted natriuretic response when saline loaded (urinary sodium excretion after saline load = 338 +/- 290 compared to 933 +/- 504 mumol min-1 of controls; P less than 0.05). The impaired natriuresis was found to be related to an increased reabsorption of sodium in the proximal tubule (proximal fractional sodium reabsorption = 88.4 +/- 3.8 compared to 81.7 +/- 4.3% of controls; P less than 0.05). These findings confirm the hypothesis that renal sodium handling abnormalities might precede ascites formation. Additional studies, however, are necessary to further define renal factors mediating the increased reabsorption of sodium in compensated liver cirrhosis.     

The acute effect of acetazolamide on glomerular filtration rate and proximal tubular reabsorption of sodium and water in normal man

The acute effects on kidney function of acetazolamide (250 mg) given intravenously were evaluated in seven healthy subjects. Glomerular filtration rate was measured as the renal clearance of 51Cr-EDTA, and fluid flow rate out of the proximal tubules was assessed by measurement of the renal lithium clearance. An 18% decline in glomerular filtration rate (ml/min) was observed after acetazolamide administration (109 +/- 16 vs 89 +/- 14, p less than 0.02), while lithium clearance (ml/min) increased by 35% (30 +/- 5 vs 38 +/- 8, p less than 0.02). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one third (79 +/- 12 vs 51 +/- 9, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (73 +/- 2 vs 58 +/- 6, p less than 0.02). Renal sodium clearance and absolute distal reabsorption of sodium increased, while fractional distal reabsorption of sodium declined. Acetazolamide reduces absolute and fractional proximal tubular reabsorption of sodium and water, and glomerular filtration rate. Primarily, this induces an increase in the output of fluid from the proximal tubules accounting for the diuretic effect of the drug. The acute fall in glomerular filtration rate is probably mediated by a temporary increase in proximal intratubular pressure and activation of the tubuloglomerular feedback mechanism.     

Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance

Abstract. Renal tubular sodium handling was evaluated in 27 non-azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldos-terone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 ± 0.11 vs. 1.29 ± 0.12%, < 0.001; 12529± 677 vs. 15707±796 μEq min^-1 1.73 m^-2 BSA, <0.005; 2384±135.2 vs. 3685±219.3 μEq min^-1 1.73 m^-2 BSA, < 0.001; 19.5±1.0 vs. 24.2±l.3%, < 0.01; 2299±127 vs. 3485±214 μEq min^-1 1.73 m^-2 BSA, <0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients ( r = 0.62; <0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 ±1.0 vs. 22.4±1.2%, <0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 ± 0.4 vs. 94.4± 0.5%,< 0.005). In both groups a correlation was found between log plasma aldosterone and distal sodium reabsorption evaluated as a per cent of absolute sodium distal delivery ( r = 0.61, <0.01 and r =0.52,<0.05 respectively).
Our study indicates that a decrease in filtered sodium load and an increase in proximal sodium reabsorption play a critical role in the impairment of renal sodium handling in non-azotemic cirrhotic patients with ascites.     

Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155/101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment caused a redistribution of tubular sodium reabsorption without a change in overall sodium excretion or body fluid compartments.     

Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules that is not fully compensated for in the distal tubules.     

Abnormal proximal tubular sodium handling in normotensive patients with chronic glomerulonephritis and normal glomerular filtration rate

In 11 normotensive patients with biopsy verified chronic glomerulonephritis and 14 controls, glomerular filtration rate (GFR), proximal and distal tubular handling of sodium determined by the lithium clearance technique, and overall tubular sodium handling determined by absolute and fractional sodium excretion were measured before, during and after intravenous infusion of a 2.5% sodium chloride solution. Patients and controls were comparable by means of GFR in that no significant differences were found between the two groups either before, during or after sodium chloride infusion. During infusion both groups responded by a decrease in GFR (p less than 0.01 in both groups). Patients exhibited an increased natriuretic response during infusion both when measured as absolute and fractional sodium excretion (p less than 0.05 both). During the infusion the increase in absolute proximal output and decrease in fractional proximal and distal tubular sodium reabsorption were more pronounced in patients than in controls (p less than 0.05). It is concluded that patients with chronic glomerulonephritis at a very early stage of the disease where blood pressure and GFR are still normal respond with exaggerated natriuresis to hypertonic sodium chloride infusion. The exaggerated natriuresis is due to a decreased fractional proximal tubular sodium reabsorption in response to sodium loading.     

Effects of Felodipine on the dog kidney: a lithium clearance study.

This study was performed in order to investigate the possible influence of sympathetic nerve activity on the effects of the dihydropyridine calcium antagonist felodipine on absolute and fractional reabsorption rates of sodium and water in proximal and distal tubular segments in the dog kidney. Clearance of 51Cr-EDTA was used as a measure of glomerular filtration rate (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance (C-Li) were used for assessing the absolute and fractional tubular reabsorption rates. Felodipine infusion into the right renal artery increased renal vascular conductance (renal blood flow divided by renal arteriovenous pressure gradient) significantly (by 9%) while GFR remained unchanged. Calculated absolute proximal reabsorption rates remained unchanged while distal sodium reabsorption rate increased significantly from 2.1 +/- 0.3 to 2.7 +/- 0.4 mmol min-1. Sodium clearance (C-Na) increased from 0.22 +/- 0.08 to 0.40 +/- 0.07 ml min-1. The alpha-adrenergic blockade with phentolamine did not affect renal haemodynamic or excretory variables, nor did it influence the haemodynamic response to felodipine. After alpha-adrenergic blockade felodipine caused an increase in C-Na from 0.28 +/- 0.06 ml min-1 to 0.63 +/- 0.04 ml min-1, which was significantly greater than that measured after felodipine alone. The distal load (C-Li) was not significantly different from that obtained after felodipine alone, but distal sodium reabsorption rate increased less significantly after alpha-adrenergic blockade. The results suggest that felodipine, by its effect on tubular flow and/or composition, activates local alpha-adrenergic reflex mechanism(s), which stimulates distal sodium reabsorption, thereby attenuating the natriuretic effect.     

Tubular handling of sodium and phosphate in non-ascitic liver cirrhosis

The renal response to a maximal water load was evaluated in eight cirrhotic patients free of ascites and without previous evidence of ascites and in seven controls. Fractional sodium reabsorption in the proximal and diluting segment was estimated by clearance methods during hypotonic diuresis. Since phosphate excretion has been proposed as a proximal marker in liver cirrhosis, sodium reabsorption in the proximal tubule was compared with phosphate fractional excretion. In spite of a normal sodium balance during the pre-study period, non-ascitic cirrhotics showed a blunted proximal natriuretic response to maximal water load. In fact sodium excretion during hypotonic diuresis was reduced (p less than 0.05) and proximal sodium reabsorption increased (p less than 0.005) in cirrhotics. Fractional phosphate excretion was not impaired in our patients, and no correlation was found between phosphate excretion and proximal sodium reabsorption, as evaluated by clearance methods. This study demonstrates that an increased reabsorption of sodium in the proximal tubule is responsible for the impaired response to maximal water load in non-ascitic cirrhotics. Abnormalities in tubular handling of phosphate may account for the dissociation between proximal sodium reabsorption and phosphate excretion during hypotonic diuresis in these patients.     

Sodium and lithium handling in the isolated hypertensive rat kidney

1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were perfused over a range of perfusion pressures. 2. Lithium clearance was used as an index of proximal tubule sodium handling. 3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 +/- 1.1% vs WKY 12.6 +/- 2.4% (mean +/- SEM); at 150 mmHg (20 kPa), SHR 17.1 +/- 1.6% vs WKY 27.0 +/- 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY. 4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished. 5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR.     

Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans

In order to assess the intrarenal mechanisms responsible for the natriuretic action of caffeine, the renal clearances of (51)Cr-EDTA [used as a measure of glomerular filtration rate (GFR)] and lithium (used as an index of end-proximal fluid delivery) were measured in eight healthy males before (control period) and immediately after (experimental period) a 400 mg oral dose of caffeine (given over 90 min) or placebo. In caffeine-treated subjects, the fractional excretion of sodium rose from 1.00+/-0.25% in the control period to 1.47+/-0.18% in the experimental period, while corresponding values on the placebo day were 1.04+/-0.16% and 0.70+/-0.07% respectively. GFR was unchanged following either caffeine or placebo. When compared with the placebo day, caffeine caused increases in lithium clearance (experimental period values: caffeine, 37+/-1 ml/min; placebo, 28+/-2 ml/min; P <0.001), the fractional excretion of lithium (caffeine, 34+/-1%; placebo, 26+/-2%; P <0.001) and the sodium/lithium clearance ratio (used as an index of the fraction of sodium delivered to the distal nephron that escapes reabsorption therein: caffeine, 4.4+/-0.3%; placebo, 2.8+/-0.2%; P <0.001). These results suggest that reduced fractional sodium reabsorption in both the proximal tubule and the distal nephron contributes to the acute natriuretic effect of caffeine. The data also confirm the importance of controlling caffeine intake when investigating renal function using lithium clearance.     

Mechanisms of the antinatriuretic action of physiological doses of angiotensin II in man

1. Angiotensin II (ANG II; 1 ng min-1 kg-1) or 5% (w/v) D-glucose (placebo) was infused in six normal male volunteers, pretreated with 500 mg of lithium carbonate, who were undergoing maximal water diuresis. 2. This dose of ANG II caused a circulating increment within the physiological range (27 +/- 4 to 48 +/- 9 pmol/l). 3. Compared with placebo, ANG II caused a significant fall in urinary sodium excretion (113 +/- 13 to 82 +/- 10 mumol/min). This antinatriuretic effect occurred without a fall in creatinine clearance (107 +/- 3 versus 113 +/- 3 ml/min). 4. ANG II caused a significant fall in fractional lithium clearance (28 +/- 2 to 23 +/- 2%). This may indicate a proximal tubular effect of ANG II. 5. ANG II also reduced fractional distal delivery [(sodium clearance plus free water clearance) divided by creatinine clearance], another measure of proximal tubular outflow. A parallel change in these two separate markers of proximal function supports an action of ANG II at this nephron segment. 6. Furthermore, the antinatriuretic effect of ANG II was unlikely to be due to stimulation of aldosterone secretion because (a) the fall in sodium excretion was temporally dissociated from the rise in aldosterone secretion, (b) potassium excretion also tended to fall during ANG II infusion and (c) aldosterone has a distal nephron effect, while, in this study, proximal nephron fractional reabsorption of sodium increased and distal nephron fractional reabsorption of sodium was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of body posture on lithium clearance

To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were measured four times at 1-week intervals: two in the supine and one in the sitting position, and one when the subject was walking around. Glomerular filtration rate was not influenced by posture changes. On the contrary, lithium clearance, which in the supine position was 30 +/- 9 ml/min (1 SD), tended to fall in the sitting position, and fell significantly to 26 +/- 5 ml/min (p less than 0.025) in walking subjects. Absolute proximal tubular reabsorption rate of fluid correspondingly rose from 83 +/- 16 to 92 +/- 15 ml/min (p less than 0.005) and sodium clearance fell from 1.52 +/- 0.81 to 1.00 +/- 0.52 ml/min (p less than 0.05) in walking subjects. Absolute distal reabsorption of sodium decreased during walking from 4052 +/- 1219 to 3449 +/- 658 mumol/min (p less than 0.025), while fractional distal reabsorption of sodium was unchanged. Our results show a rise in proximal tubular reabsorption during moderate physical activity. Hence, when renal tubular function is studied with the lithium clearance method, standardization of posture and physical activity is important. In such studies physical activity such as walking should particularly be avoided.     

Effect of intravenous sodium loading on renal tubular handling of sodium and water in unilaterally nephrectomized humans

Glomerular filtration rate (GFR), proximal absolute and fractional reabsorption of isotonic fluid (PAR and PFR) and distal absolute and fractional reabsorption of sodium (DARNa and DFRNa) were measured using the lithium clearance technique in nine unilaterally nephrectomized people (UNP) 1-11 years postnephrectomy and in 14 controls before, during and after an intravenous sodium load. Glomerular filtration rate per kidney was 53% higher in UNP and decreased slightly but significantly (p less than 0.01) in both groups during sodium loading. The PAR per kidney was significantly higher in UNP (p less than 0.01) but PFR was the same as in controls. Both groups responded to sodium loading with a significant decrease in both PAR and PFR. In UNP, DARNa per kidney was significantly higher than in controls (p less than 0.01) but DFRNa was the same in the two groups. Sodium loading resulted in a further increase in DARNa and a decrease in DFRNa in both groups. Both groups responded to sodium loading with a similar increase in fractional sodium excretion. It is concluded that unilateral nephrectomy is followed by an increase in GFR, PAR and DARNa but with maintenance of fractional reabsorption in both proximal and distal tubuli. In response to an intravenous sodium load, the remnant kidney is able to respond in a normal way with a further increase in DARNa. The adjustments necessary to maintain sodium balance after unilateral nephrectomy take place in both proximal and distal tubuli.     

Abnormal glomerular and tubular function during angiotensin converting enzyme inhibition in renovascular hypertension evaluated by the lithium clearance method

Glomerular filtration rate (GFR) and tubular function were measured by means of the lithium clearance technique in 14 patients with renovascular hypertension (RVH) and eight patients with essential hypertension (EH) before and after oral administration of captopril 25 mg. In RVH captopril reduced 51-Cr-EDTA clearance (67.3 (median) to 47.5 ml min-1, P less than 0.01), proximal absolute reabsorption of fluid (53.9 to 41.5 ml min-1, P less than 0.01) and distal absolute reabsorption of sodium (2195 to 1402 mumol min-1, P less than 0.01), whereas proximal fractional reabsorption increased slightly (77.5 to 80.2%, P less than 0.02). In EH, however, these parameters were practically unaffected by captopril. In both RVH and EH plasma concentrations of angiotensin II and aldosterone were reduced after captopril, but atrial natriuretic peptide in plasma and urinary excretion rate of prostaglandin E2 were unchanged. Blood pressure decreased after captopril in both groups, but the maximum fall in systolic BP was more pronounced in RVH (22%) than EH (13%). It is concluded that angiotensin converting enzyme inhibition markedly reduced absolute reabsorption in both the proximal and distal tubules in RVH, in contrast to EH, predominantly due to fall in the GFR, and that the slight increase in proximal fractional reabsorption may be attributed to a reduction in the hydrostatic pressure in the peritubular vessels.     

Effects of morphine on the renal handling of sodium and lithium in conscious rats

The present study was carried out in order to assess the renal response to i.v. morphine in the rat, particularly the effects on tubular handling of sodium and lithium. Rats were prepared surgically with arterial and venous catheters and bladder cannulas. Clearance experiments and measurements of blood pressure and heart rate were carried out at least 4 days after surgery in unanesthetized animals. Intravenous administration of morphine (4 mg/kg b.wt.) caused a decrease in fractional sodium excretion, (at 90 min after injection, vehicle, 2.49 +/- 0.30% vs. morphine, 1.12 +/- 0.17%, P less than .05), in the absence of significant changes in systemic hemodynamics or glomerular filtration rate. This effect was prevented by pretreatment with naloxone. Enhanced proximal tubular reabsorption of sodium was considered as a possible explanation for the decrease in sodium excretion which followed morphine administration. Proximal tubular fluid reabsorption was estimated utilizing the lithium clearance method. Results indicated a reduction in fractional excretion of lithium by morphine administration (at 90 min, vehicle, 34.2 +/- 3.3% vs. morphine, 18.8 +/- 2.3%, P less than .05), which was also prevented by naloxone pretreatment. It is concluded that, under the present experimental conditions, morphine enhances tubular reabsorption of sodium by an opiate receptor-dependent mechanism and that this effect is, at least in part, localized in the proximal tubule.     

Amiloride-sensitive lithium reabsorption in rats: a micropuncture study.

It has been suggested that in sodium-restricted rats lithium is being reabsorbed in the collecting tubule, and that such reabsorption can be prevented by amiloride. We studied these options in rats by means of cortical micropuncture. Indeed, an important fraction of the filtered lithium (10.5%) was reabsorbed beyond the early distal tubule in sodium-restricted rats. Amiloride infusion abolished this reabsorption. The dosage used did not affect the reabsorption of water, sodium and lithium in the proximal tubule, and also did not change the reabsorption of water and sodium in the loop segment. However, the reabsorption of lithium in this segment tended to be higher during amiloride (P = .06), and the delivery of lithium to the early distal puncture site was significantly less (26.1 +/- 1.2%) than in the control rats (31.4 +/- 1.8%, P < .05). The reason for this apparent increase in lithium reabsorption in the loop segment is not clear. Interestingly, amiloride increased urine flow and decreased urine osmolality. The mechanism underlying this effect needs further exploration. We conclude that in sodium-restricted rats lithium reabsorption beyond the early distal tubule level occurs. Lithium clearance data therefore underestimate end-proximal delivery under these conditions. Lithium reabsorption beyond the early distal tubule can be prevented by amiloride treatment. However, because amiloride may stimulate lithium reabsorption further upstream, lithium clearance data obtained during amiloride infusion may still underestimate end-proximal delivery of water and sodium.     

The syndrome of hypertension and hyperkalemia with normal GFR (Gordon's syndrome): is there increased proximal sodium reabsorption?

The syndrome of hypertension and hyperkalemia, hyperchloremic acidosis with normal glomerular filtration rate (Gordon's syndrome) is characterised by volume expansion, suppressed renin and reduced mineralocorticoid-induced renal clearance of potassium. The clinical and biochemical defects are aggravated by high salt diet and corrected by low salt diet, leading to the hypothesis of excessive sodium reabsorption in the nephron proximal to where aldosterone acts. In this study, we used lithium clearance as a marker of proximal sodium reabsorption in three patients with Gordon's syndrome, in order to further localise the site in the nephron of defective sodium handling. Fractional excretion of lithium was decreased, and absolute and fractional proximal reabsorption of sodium was increased compared to normal controls. In addition, absolute distal reabsorption of sodium was decreased, consistent with decreased mineralocorticoid activity. Fractional excretion of potassium was markedly decreased and did not rise with increased distal delivery of sodium during saline infusion. However, after severe dietary sodium restriction had elevated plasma aldosterone (lowering plasma potassium levels to normal), fractional excretion of potassium was raised by saline infusion. Reduced lithium clearance in patients with Gordon's syndrome supports the hypothesis of increased proximal sodium reabsorption in this condition.     

Renal sodium handling in patients with normal pressure glaucoma

Low BP (blood pressure) is a recognized risk factor for some patients with NPG (normal pressure glaucoma). We have shown previously that patients with orthostasis have impaired circadian renal handling of sodium, which may contribute to the low BP. Therefore the aim of the present study was to examine the renal handling of sodium, the circadian variations in BP and the neurohormonal response to an orthostatic test in a selected subpopulation of 18 patients with NPG with vasospastic and orthostatic symptoms, and in 24 healthy control subjects. The variations in BP and renal tubular sodium handling were evaluated using 24 h ambulatory BP recordings, 24 h urine collections and determination of endogenous lithium clearance as a marker of proximal sodium reabsorption. The neurohormonal and BP responses to changes in posture were also determined in a 30 min orthostatic test. This selected group of patients with NPG had lower 24 h ambulatory BPs (P<0.001), and a more pronounced fall in BP when assuming an upright position (P<0.001) compared with controls. FE(Li) (fractional excretion of lithium) was higher in patients with NPG than controls during the day (36.6+/-21.8 compared with 20.4+/-8.7% respectively; P<0.01; values are means+/-S.D.) as well as during the night (38.8+/-41.9 compared with 19.7+/-10.8% respectively; P<0.02), suggesting a reduced reabsorption of sodium in the proximal tubule. This was compensated for by an increased distal reabsorption of sodium in patients with NPG (P<0.01). These data demonstrate that patients with vasospastic NPG have a high excretion of lithium, suggesting reduced sodium reabsorption in the proximal tubule, in spite of a low BP. The abnormal renal sodium handling might contribute to the maintenance of arterial hypotension and progression of the optic nerve damage in these patients.     

Effect of synthetic atrial natriuretic factor on superficial and deep proximal tubule sodium reabsorption

The effects of synthetic atrial natriuretic factor (ANF) on sodium reabsorption by deep and superficial proximal tubules were examined in the rat. In response to ANF infusion (4 micrograms/kg/hr), the urinary fractional excretion of sodium increased from 1.21% +/- 0.53% to 3.48% +/- 0.48%, p less than 0.05 (n = 12). Fractional delivery of sodium (FDNa) from the deep proximal tubule was 25.9% +/- 3.7% before and 33.7% +/- 3.4% after ANF infusion. In time control animals, FDNa from deep proximal tubules was 34.3% +/- 3.0% and 28.5% +/- 4.0% respectively (n = 12). The change in FDNa from deep proximal tubules during ANF infusion (increase of 7.8% +/- 3.9%) was significantly different from the change in control animals (decrease of 5.8% +/- 3.1%) (ANF infusion vs control, delta 13.7% +/- 4.9%, p less than 0.05). No significant change was observed in FDNa in the superficial proximal tubule either during ANF infusion or in control animals. In summary, ANF infusion increased urinary fractional sodium excretion; however, fractional sodium reabsorption by the proximal tubule of superficial nephrons was unchanged. In contrast, sodium delivery to the point of micropuncture in the descending limb of Henle's loop of deep nephrons was increased, as compared with controls, suggesting inhibition of sodium reabsorption by proximal tubules of deep nephrons.