Distal Sodium Reabsorption Research Articles

Correction of Hypokalemia in Bartter's Syndrome by Enalapril

Seven patients with Bartter's syndrome were investigated before and after 3 months' treatment by enalapril. Serum potassium rose from 2.4 +/- 0.5 to 3.9 +/- 0.6 mmol/L. In all patients, serum magnesium rose and bicarbonate fell. Hormonal changes were as suspected: a further stimulation of renin and a decline in aldosterone. The BP sensitivity to angiotensin II normalized in the five patients in whom the test was performed. Clearance studies during maximal water diuresis, performed in four patients, were compatible with a high proximal fractional tubular sodium reabsorption and a relatively low distal fractional sodium reabsorption. Fractional free water excretion after furosemide was also low, confirming the concept of a primary sodium reabsorption defect in the furosemide-insensitive part of the nephron in Bartter's syndrome. The only consistent change after enalapril was a further decline in distal fractional sodium reabsorption. Initiation of therapy produced a BP fall in each subject. Clinical important hypotension associated with oliguria was seen twice, but these reactions were short-lasting. The BP rose to pretreatment values within 72 hours, despite continuation of converting-enzyme inhibition. Renal function recovered, though a moderate fall in function persisted. No other side effects were noticed. We conclude that converting-enzyme inhibition improves the potassium metabolism of patients with Bartter's syndrome, without ameliorating the abnormal renal sodium handling.

Effect of dietary sodium chloride and posture on plasma immunoreactive atrial natriuretic peptide concentrations in man.

The effect of changes of dietary sodium chloride intake and posture on plasma atrial natriuretic peptide concentration and renal function was studied in 11 normal human volunteers. Plasma atrial natriuretic peptide concentration was higher in the upright posture on a high than it was on a medium or low salt diet. On the medium and high but not on the low salt diet the concentration increased significantly on adoption of the supine posture. Creatinine, sodium, lithium and fractional lithium clearances, fractional distal sodium excretion and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, were significantly higher on the high than on the low salt diet. The medium salt intake gave intermediate values. Heart rate while upright was significantly higher on the low than on either the medium or the high salt diets. Systolic blood pressure was unaffected by salt intake. Diastolic blood pressure in the supine position was significantly higher on the low than on the medium or high salt diets. Both plasma noradrenaline concentrations and plasma renin activity were significantly higher on the low than on the high salt diet. Values on the medium salt intake were intermediate. Plasma concentrations of both hormones were higher in the upright than in the supine posture on all three salt intakes. The data are consistent with the hypothesis that atrial natriuretic peptide contributes to the cardiovascular and renal adjustments to changes in dietary sodium chloride, and the possible role of the peptide is discussed.

Adrenergic receptors and sodium reabsorption in normotensive subjects as related to salt sensitivity.

We have studied proximal tubular sodium reabsorption as measured by lithium clearance, alpha-2 and beta-2 adrenergic receptors on circulating platelets and lymphocytes, respectively, and urinary aldosterone after variations of sodium intake in 24 normotensive volunteers. Fractional lithium clearance was 14.8% +/- 2.64 under a high salt diet of 200 mmol per day. After a low salt diet of 50 mmol/d for two weeks fractional lithium clearance did not change significantly (13.3% +/- 3.35). There were no correlations between alpha-2 adrenergic receptors, beta-2 adrenergic receptors or the alpha-2/beta-2 ratio and fractional lithium clearance, irrespective of the high or low salt diet. In contrast, a significant correlation was found between urinary aldosterone excretion and alpha-2 receptor densities under low salt diet (r = -0.55, n = 17, p less than 0.02). There were no correlations between beta-2 adrenoceptor density, alpha-2/beta-2 ratio and urinary aldosterone during high or low salt diet. Whereas our results are inconclusive about the value of lithium clearance determinations as a measure of proximal tubular sodium reabsorption during variations of sodium intake, we conclude, that alpha-adrenoceptor density, as measured on circulating blood cells, may possibly be representative for alpha-adrenergic equipment of the kidney. The inverse correlation between urinary aldosterone excretion in subjects equilibrated on a low salt diet of 50 mmol/d and alpha-2 adrenoceptor densities could be interpreted as an indirect evidence, that those subjects with a high alpha-2 adrenoceptor equipment show a high proximal tubular sodium reabsorption and thus can afford a low rate of aldosterone mediated distal tubular sodium reabsorption to maintain sodium balance. Our results are thus in accord with our previous hypothesis, that different receptor equipment of individual subjects may cause marked differences in sodium handling by the kidney. These differences may be responsible, at least in part, for the degree of salt sensitivity in individual subjects.

The effect of converting enzyme inhibition on the enhanced proximal sodium reabsorption induced by chronic diuretic treatment in patients with essential hypertension.

During chronic chlorthalidone treatment of patients with essential hypertension, distal tubular sodium reabsorption is continuously inhibited. At the same time, sodium balance is maintained by an increase of the proximal tubular sodium reabsorption. In the present study, we investigated whether this increase is caused by a stimulated renin-angiotensin system (RAS). For this purpose, the renal effects of converting enzyme inhibition (CEI) were evaluated in 12 patients with essential hypertension who remained hypertensive despite chronic chlorthalidone treatment. After 6 weeks of chlorthalidone, an intravenous injection of 10 mg enalaprilic acid decreased the mean arterial pressure (MAP) from 110 to 102 mm Hg. The effective renal plasma flow (ERPF) increased. However, glomerular filtration rate (GFR) and the fractional excretions of sodium, lithium and free water did not change significantly. After 2 additional weeks of chlorthalidone combined with enalapril 20 mg b.i.d., MAP fell to 90 mm Hg, ERPF remained elevated and plasma aldosterone concentration decreased. As in the acute study, no significant changes were detected in the GFR and the fractional excretions of sodium, lithium or free water. Extracellular fluid volume was not diminished during these 2 weeks. Fractional proximal sodium reabsorption during chronic chlorthalidone therapy was higher when calculated from free water clearance (91%) than from the lithium clearance (71%), but neither of the two were affected by acute or chronic CEI. The results of this study suggest that during chronic diuretic treatment, maintenance of sodium balance by increased proximal reabsorption is not dependent on the stimulated RAS, or alternatively, that this function of the RAS is exactly counterbalanced by another effect of CEI, possibly by the fall in blood pressure.

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.

Renal function during recovery from minimal lesions nephrotic syndrome.

We followed renal function through the natriuretic phase of 6 occasions of drug-induced recovery from minimal lesions nephrotic syndrome (MLNS). Protein excretion started to fall 1-3 days prior to the start of the natriuresis. The natriuresis was accompanied by a rise in glomerular filtration rate (GFR, inulin clearance). The filtration fraction, calculated from the GFR and the p-aminohippurate clearance, rose steadily in 5 subjects in whom it was low before therapy. Proximal and distal sodium reabsorption fractions, estimated from the changes in maximum free water clearance, fell, and fractional sodium, lithium, uric acid and free water clearance rose. At the time of these changes plasma protein had hardly risen, whereas renin activity was down. These results are in agreement with the notion that the sodium retention of MLNS is due to a renal defect. Repair of the glomerular filter, evident from the disappearance of proteinuria and the rise in filtration fraction, apparently normalizes the elevated tubular sodium reabsorption proximal to the macula densa, which leads to a fall in renin release.

Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method.

The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium clearance (26 +/- 4%), lithium clearance (9 +/- 2%) and fractional lithium clearance (8 +/- 2%) was seen, as compared to the contralateral kidney with preserved innervation. Calculated absolute proximal reabsorption rate decreased significantly by 7 +/- 2%, while calculated absolute rates of distal reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during alterations in renal nerve activity occurred without measurable changes in renal blood flow (RBF) and glomerular filtration rate (GFR). Administration of amiloride had no significant effect either on the lithium clearance, RBF or GFR, while the sodium excretion rate increased and potassium excretion rate decreased, supporting that significant distal lithium reabsorption did not occur under the present experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal sodium handling in normal humans subjected to low, normal, and extremely high sodium supplies.

We studied renal sodium handling, extracellular fluid volume (ECFV), plasma renin activity, aldosterone and norepinephrine, and blood pressure in eight healthy volunteers after equilibration on intakes of 20, 200, and 1,128 +/- 141 meq sodium, respectively. Renal sodium handling was assessed by means of clearance studies during maximal water diuresis and lithium clearance. Urinary sodium excretions were 22 +/- 4, 202 +/- 19, and 1,052 +/- 86 meq/day. From the lower to the upper sodium intake level, 24-h creatinine clearance rose from 111 +/- 7 to 136 +/- 11 ml/min and inulin clearance from 103 +/- 9 to 129 +/- 9 ml/min, whereas proximal and distal fractional sodium reabsorption (FSRprox and FSRdist, respectively) fell from 86.8 +/- 1.3 to 79.0 +/- 2.7% and from 96.5 +/- 0.5 to 76.0 +/- 1.9%, respectively. During the normal sodium intake (200 meq), intermediate values were recorded. The changes in fractional lithium clearance were less consistent but correlated with FSRprox (r = 0.78, P less than 0.001) and not with FSRdist. Major changes in plasma renin activity, aldosterone, and, to a lesser extent, norepinephrine accompanied these changes in kidney function, displaying inverse and exponential correlations with daily sodium excretion and ECFV. No consistent rise in blood pressure was detected. These observations indicate that in healthy humans renal adaptation to vast variations in sodium intake includes resetting of glomerular filtration rate, FSRprox, and, in particular, FSRdist. Alterations in neurohumoral factors may play a dominant role in this adaptation.

Effects of Acute Volume Loading on Kidney Function in Patients with Essential Hypertension, as Estimated by the Lithium Clearance Method

This study investigated the mechanism underlying the exaggerated natriuresis seen in patients with essential hypertension. The study used the lithium clearance method, which permits accurate determination of both proximal and distal sodium reabsorption in man. One litre of isotonic sodium chloride, intravenously (i.v.), produced a significant increase in sodium excretion in patients with essential hypertension, both during and after the infusion. This increase in sodium excretion was accompanied by a significant increase in the clearance of lithium, indicating an increased output of isotonic fluid from the proximal tubules. The calculated distal reabsorption of sodium increased during the natriuresis. In the normotensive controls, sodium excretion increased only after the infusion of 1 l isotonic saline. This was accompanied by a modest increase in absolute distal sodium reabsorption. However, when the amount of saline was increased to 2 l, similar changes to those seen in hypertensives given 1 l of saline occurred in normotensive subjects. Furthermore, chronic antihypertensive treatment abolished the phenomenon of exaggerated natriuresis. It is concluded that the exaggerated natriuresis represents the normal response to sodium loading being reset to a lower level. This resetting may be a secondary consequence of the high blood pressure, since lowering the pressure abolishes the phenomenon.

Tubular action of diuretics: Distal effects on electrolyte transport and acidification

We used clearance and free-flow micropuncture techniques to evaluate the influence of several diuretic agents, given both individually and in various combinations, on transport of sodium, potassium, and fluid, and on acidification and ammonium transport, within the distal tubule of the rat kidney. The loop diuretics, furosemide and piretanide, sharply increased fractional delivery of fluid, sodium, and potassium into the distal tubule, and, as a result, sodium reabsorption and potassium secretion were enhanced in this nephron segment. These two drugs also stimulated urinary acidification and increased urinary phosphate, titratable acid, and ammonium excretion. These effects took place both within the loop of Henle and along the distal tubule. Amiloride and triamterene alone inhibited distal tubular sodium reabsorption and potassium secretion, and, when given with one of the loop diuretics, suppressed both the kaliuresis and the increased acid and ammonium excretion induced by the latter agents. Hydrochlorothiazide and tizolemide inhibited sodium reabsorption within the distal tubule, and were associated with a stimulation of potassium secretion within this segment. Addition of one of these two latter distally acting agents to either of the loop diuretics led to a further augmentation of sodium excretion, but to a reduction of potassium excretion, compared to the responses seen after the loop diuretics alone.

Mechanisms of angiotensin II natriuresis and antinatriuresis.

The aim of this study was to determine the role of changes in renal arterial pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (ANG II). In seven anesthetized dogs, endogenous ANG II formation was blocked with captopril, and ANG II was infused intravenously at rates of 5-1,215 ng X kg-1 X min-1 while RAP was either servo-controlled at the preinfusion level or permitted to increase. When RAP was servo-controlled, ANG II infusion at all rates from 5-1,215 ng X kg-1 X min-1 decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa) while increasing fractional reabsorption of lithium (FRLi) (an index of proximal tubular fractional sodium reabsorption) and causing no change in calculated distal tubule fractional sodium reabsorption (FRDNa). When RAP was permitted to increase, ANG II infusion rates up to 45 ng X kg-1. min-1 also decreased UNaV and FENa while increasing FRLi and causing no change in FRDNa. However, at 135 ng X kg-1 X min-1 and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though renal blood flow and filtration fraction were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during ANG II infusion compared with when RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of ANG II cause antinatriuresis when RAP is prevented from increasing.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of acute and short-time antibiotic treatment on renal lithium elimination and serum lithium levels in the rat.

Male Wistar rats received a single stomach load (10 ml/kg) of a 150 mmol LiCl solution, either alone or together with tetracycline (33.5 mg/10 ml), ampicillin (33.5 mg/10 ml), or metronidazole (15 mg/10 ml). Urine was collected 1-5 hours after administration and blood samples were drawn after 1, 6, and 24 hours. All antibiotics caused a reduction in urinary lithium excretion but did not affect renal lithium clearance. Serum lithium levels were reduced by tetracycline and metronidazole 6 hours after administration but increased after 24 hours. Additional experiments including frequent mapping of serum lithium levels confirmed these findings. Tetracycline, also reduced renal sodium clearance and increased distal sodium reabsorption. Short-term daily treatment during one week with tetracycline or metronidazole showed that these initial changes were only transient, since after treatment for one week no differences could be observed between antibiotic-treated rats and control rats. The results indicate that antibiotics may cause a delay but no decrease of the gastrointestinal absorption of lithium and that they do not affect renal lithium clearance. Signs of lithium intoxication during combined use of lithium and antibiotics are therefore probably not caused by a renal interaction mechanism affecting the renal lithium clearance.

Proximal tubular transport and urinary excretion of sodium after renal denervation in sodium depleted rats.

The effect of unilateral renal denervation on renal handling of water, sodium and potassium was studied with clearance and micropuncture techniques in sodium depleted anaesthetized rats in the nondiuretic state. In clearance experiments renal denervation resulted in a +140 and +320% increase in urine flow and potassium excretion, but sodium excretion of innervated (I) and denervated (D) kidneys was similar (I: 12.0 +/- 2.0, D: 14.0 +/- 3.6 nM . min-1 . g-1; NS). However, upon the loop diuretic furosemide (1 mg . kg-1), a marked denervation natriuresis was observed (I: 2.8 +/- 0.9, D: 5.9 +/- 1.0 microM . min-1; P less than 0.05) and denervation diuresis and kaliuresis persisted, too (+95 and +60%, respectively). Micropuncture results revealed that fractional reabsorption of filtrate to late proximal puncture site was depressed by renal denervation from 62 to 49% while no change in time control rats was seen (64 +/- 2 vs. 64 +/- 1%; NS). In micropuncture experiments besides augmented urine flow (+82%) from D kidneys also a small denervation natriuresis was present (I: 21.6 +/- 6.4, D: 29.2 +/- 7.0 nM . min-1; P less than 0.05). It is concluded that the lack or marked attenuation of denervation natriuresis in sodium depleted rats were the result of an almost complete compensatory distal reabsorption of the excess sodium (but not of water and potassium) leaving the proximal tubule after denervation. The distal adaptive response can be overcome by furosemide.

Angiotensin II natriuresis and antinatriuresis: role of renal artery pressure, renal hemodynamics, and tubular reabsorption.

The aim of this study was to determine the role of changes in renal artery pressure (RAP), renal hemodynamics, and tubular reabsorption in mediating the natriuretic and antinatriuretic actions of angiotensin II (AII). In anesthetized dogs, endogenous AII formation was blocked with SQ-14225 and AII was infused i.v. at rates of 5-1215 ng/kg/min while RAP was either servo-controlled at the normal level or permitted to increase. When RAP was servo-controlled to prevent a rise i RAP, AII infusion at all rates from 5-1215 ng/kg/min decreased urinary sodium excretion (UNaV) and fractional sodium excretion (FENa), while increasing fractional reabsorption of lithium (FRLi), an index of proximal tubule fractional sodium reabsorption and distal fractional sodium reabsorption (FRDNa): When RAP was permitted to increase, AII infusion rates up to 45 ng/kg/min decreased UNaV, and FENa, while increasing FRLi and FRDNa. However, at 135 ng/kg/min and above, UNaV and FENa increased while FRLi and FRDNa decreased when RAP was allowed to rise, even though RBF and FF were not substantially different from the values observed when RAP was servo-controlled. Filtered sodium load was slightly higher when RAP was permitted to increase during AII infusion, compared to the dogs in which RAP was servo-controlled, although the differences were not statistically significant. Thus, even very large doses of AII cause antinatriuresis when RAP was prevented from increasing. The natriuretic effect of high dose of AII is caused by increased RAP which decreases fractional sodium reabsorption in proximal and distal tubules and causes slight increases in sodium delivery to the tubules.

Antihypertensive and renal effects of nicardipine.

Both the acute blood pressure lowering and renal effects of the calcium antagonist nicardipine and those after 1 week's treatment were investigated in 10 normotensive volunteers and in 10 patients with mild to moderate essential hypertension. After 1 week of placebo, nicardipine was administered orally for 1 week (20 mg three times daily), Investigations, done on the first and last day of nicardipine treatment were compared with those on the last day of placebo. During water loading, nicardipine increased urinary volume and urinary excretion of sodium significantly after 1 week nicardipine treatment. In the normotensive group the natriuretic effect was caused by a decrease of fractional proximal and distal reabsorption of sodium. In the hypertensive group the natriuresis was achieved mainly by an increase of the rate of glomerular filtration (GFR) and also by a slight distal effect. Our results show that nicardipine had natriuretic effects. There were trends suggesting that the renal effects may differ between patients with essential hypertension and normotensive volunteers, but the findings might also be related to differences in age between the groups.

Failure of increased sodium avidity to facilitate renal acid excretion in dogs fed sulfuric acid

Previous studies have suggested that the increment in renal acid excretion caused by sulfuric acid feeding is mediated solely by an interplay between the sulfate-induced increase in distal sodium delivery and the gradual augmentation of distal sodium reabsorption that occurs as sodium losses accumulate. This hypothesis predicts that if distal sodium reabsorption were stimulated sufficiently prior to the administration of sulfuric acid, excretion of the hydrogen ion load would occur promptly, thus obviating the fall in plasma bicarbonate or loss of cation that normally occurs. To test this prediction, we fed sulfuric acid (7 mEq of H+/kg/day) to dogs in which distal sodium avidity had been enhanced prior to acid feeding either by diuretic-induced sodium depletion (N = 6) or by deoxycorticosterone acetate 7.5 mg, twice a day and a low-sodium diet (N = 8). Contrary to expectation, over the first 3 days of acid feeding there was a significant fall in plasma bicarbonate (7.1 and 7.5 mEq/liter) and an increase in urinary sodium excretion (48 mEq in both groups). Moreover, changes in both plasma bicarbonate and urinary sodium excretion were similar to those observed previously (5.9 mEq/liter and 46 mEq, respectively) in normal dogs fed the same dose of sulfuric acid.

Distal tubular sodium reabsorption in the developing rat kidney

The immature kidney has a blunted natriuretic response to saline loading. to localize the high fractional Na reabsorption in the developing nephron, we determined Na delivery to the early distal tubule (EDT) and the fraction of filtered Na remaining in the tubular fluid [(TF/P)Na/In] in the EDT and late distal tubule (LDT) in 24- and 40-day-old hydropenic (HP) and volume-expanded (VE) rats. During HP the (TF/P)Na/In ratio in EDT was significantly higher in the younger rats (12.6 +/- 2.0%) than in the older rats (4.2 +/- 0.6%), but because of a lower SNGFR in the younger rats th Na delivery to EDT was the same in both age groups. The (TF/P)Na/In ratio in LDT was not different in 24- and 40-day-old HP rats (1.1 +/- 0.4 and 1.7 +/- 0.3%, respectively). During VE th (TF/P)Na/In ratio in LDT was significantly lower in 24- (3.0 +/- 0.7%) than in 40-day-old rats (8.3 +/- 1.1%). The (TF/P)Na/In ratio in LDT correlated well with the urinary fractional Na excretion. It is concluded that the Na reabsorption capacity of the developing nephron is more efficient in the distal tubule than in the more proximal tubular segments.

Renal handling of water and sodium in children with proximal and distal renal tabular acidosis.

Renal sodium wasting has been observed in both proximal and distal renal tubular acidosis (RTA), although few studies have been reported indicating the tubular localization of such a defect. The use of clearance methodology during hypotonic saline diuresis may give an indirect estimate of proximal tubular reabsorption of sodium, sodium reabsorption at the diluting segments and proportion of sodium load reabsorbed distally. This study was carried out in 17 normal children, in 9 children with proximal RTA, associated in all but one with the Fanconi syndrome, and in 5 children with primary distal RTA. Patients with proximal RTA presented mainly an impaired reabsorption of sodium in the proximal tubule, which was in great part but not completely compensated by an absolute increase in distal sodium reabsorption. Patients with distal RTA showed normal reabsorption of sodium in the proximal tubule but they were unable to reabsorb completely the load of sodium escaping proximal reabsorption due to a defect of sodium reabsorption in the distal diluting segments. These results indicate that the classification of RTA in proximal and distal types is also valid according to the differences found in the tubular handling of water and sodium.

Postnatal development of renal sodium handling in premature infants

To estimate the contribution of the specific defect in proximal and distal tubular reabsorption of sodium to renal salt wasting, fractional sodium excretion, distal tubular sodium delivery, and distal tubular sodium reabsorption were determined in 11 healthy premature infants. The study was performed on the seventh day and at weekly intervals thereafter up to the sixth week of life. Sodium clearance and fractional sodium excretion decreased significantly with increasing postnatal age (P less than 0.001). There was no significant alteration in either osmolar or free-water clearances. Distal tubular sodium delivery steadily decreased from 4.96 +/- 0.66 (mean +/- SE) in the first week to 3.3 +/- 0.41 ml/minute/dl GFR in the sixth week of life (P less than 0.05). Distal tubular sodium reabsorption was 69.5 +/- 2.36% in the first week, then rose significantly to reach a value of 83.7 +/- 1.85% in the second week (P less than 0.001) and remained practically unchanged thereafter. It is suggested that the rapid improvement of distal tubular sodium reabsorption in premature infants might result from forced stimulation by the excessively activated renin-angiotensin-aldosterone system.

Normotensive hyperreninemia in systemic lupus erythematosus. An indicator of tubular dysfunction.

High plasma renin activity (PRA) was found in 16 of 42 randomly selected nonuremic systemic lupus erythematosus (SLE) patients. Mild hypertension was present in 3 of the 16.6 high-PRA and 10 normal-PRA patients were admitted to a metabolic ward. Salt restriction produced a disproportionate rise in both PRA and aldosterone, a decrease in glomerular filtration rate (GFR) and a slightly greater negative sodium balance in the group with high PRA. Potassium excretion was less than intake in both groups. Balance studies were performed in 6 additional high-PRA patients before and during indomethacin administration (150 mg/24 h). PRA and aldosterone were markedly suppressed by indomethacin. UnaV was significantly greater than in the control period despite of the 28% reduction in GFR. These results suggest that high PRA is secondary to impaired distal tubular sodium reabsorption. Such a defect could be responsible for the relatively low frequency of hypertension in lupus nephritis.