Effect of hypoxia on renal prostaglandin E2 production in human and rat neonates.

Effect of hypoxia on renal prostaglandin E2 (PGE2) production was shown in asphyxic newborn infants and experimental hypoxic rats. In asphyxic infants, at postnatal day 1, the urinary excretion of PGE2 in severe asphyxia (1.00 +/- 0.19 pg/kg/min, n = 10) was lower than that of the mild asphyxia (2.15 +/- 0.18 pg/kg/min, n = 10) or normal newborn infants (2.65 +/- 0.25 pg/kg/min, n = 8) (p less than 0.01). The urinary excretion of PGE2 was inversely correlated with the urinary N-acetyl-beta-D-glucosaminidase (r = -0.84, p less than 0.01). The urine volume in mild asphyxia (0.04 +/- 0.005 ml/kg/min) was higher in comparison to normal newborn infants (0.026 +/- 0.002 ml/kg/min) (p less than 0.01), but had no correlation with the urinary excretion of PGE2. In experimental hypoxic rats, the renal PGE2 concentration increased from 0.19 +/- 0.02 ng/mg protein to the maximum level of 0.59 +/- 0.03 ng/mg protein at 10 min of hypoxia. The renal PGE2 concentration then decreased to the minimum level (0.105 +/- 0.02 ng/mg protein) at 24 h after 20 min hypoxia. The renal ATP rapidly decreased during 20 min hypoxia, and gradually increased to 55.1 +/- 6.2 nmol/mg protein at 24 h after 20 min hypoxia, which recovered only about 60% of the control level. It seems likely that renal PGE2 does not play a major role in diuresis in mild birth asphyxia and that severe birth asphyxia suppresses the renal PGE2 production in early neonatal period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of the immaturity of the ADH-dependent cAMP system in conscious newborn piglets--possible impairing effects of renal prostaglandins

In 24 conscious newborn piglets the effects of 20 micrograms/kg body weight IV 1-deamino-8-D-arginine-vasopressin (DDAVP) in group 1, 5 mg/kg PO indomethacin in group 2, and the combined effects of both drugs in group 3 were studied by measuring urinary flow rate, urinary osmolality, creatinine clearance, total urinary and nephrogenous cyclic-adenosine 3':5'-monophosphate (cAMP) excretion, medullary cAMP content, and renal prostaglandin (PG)E2 and PGF2 alpha, excretion. DDAVP alone had no significant effects on ther above parameters, whereas indomethacin alone reduced only the PG excretion significantly. When both drugs were administered simultaneously, urinary concentration increased significantly (urinary flow rate decreased from 2.4 +/- 0.4 to 1.4 +/- 0.3 ml/hr (means +/- S.E.), and urinary osmolality increased from 444 +/- 29 to 552 +/- 33 mOsm/liter). Total urinary and nephrogenous cAMP excretion increased from 590 +/- 48 to 854 +/- 78 and 302 +/- 36 to 590 +/- 81 pmoles/hr/g kidney weight, respectively, whereas PGE2 and PGF2 alpha decreased from 249 +/- 33 to 19 +/- 4 and 192 +/- 32 to 43 +/- 7 pg/hr/g kidney weight, respectively. In addition, medullary cAMP content was considerably higher in group 3 (2010 +/- 200 pmoles/g medulla) than that observed in the control (1187 +/- 137), DDAVP (1218 +/- 115), and indomethacin (1230 +/- 168) groups.     

Urinary prostaglandins and the effect of indomethacin on phosphate excretion in children with hypophosphatemic rickets

We recently reported the urinary prostaglandin E(2)/creatinine ratio (PGE(2)/Cr) was markedly elevated in Hyp mice, the animal model for X-linked hypophosphatemia, compared with control mice. We provided evidence for altered prostaglandin production mediating the phosphaturia and that indomethacin decreases urinary phosphate excretion in Hyp mice but not control mice. To determine the levels of urinary PGE(2)/Cr, the safety and efficacy of indomethacin on phosphate excretion in children with hypophosphatemic rickets (HPR), a prospective clinical trial was performed in 16 children with HPR and 16 age- and gender-matched healthy controls. Urinary PGE(2)/Cr excretion was determined on a 24 h timed urine collection. A randomized cross over, placebo versus indomethacin, clinical trial was performed in the 16 children with HPR. There was no difference in urinary PGE(2)/Cr excretion between controls and patients with HPR. In children with HPR, indomethacin treatment for 3 mo had no significant effect on serum phosphorus or urinary phosphate excretion. In conclusion, urinary prostaglandin excretion is similar in children with HPR compared with controls. Indomethacin had no significant effect on serum phosphorus or urinary phosphate excretion in children with HPR.     

Long-term course of 6 boys with congenital nephrogenic diabetes insipidus

From 1975-1986 6 boys with congenital nephrogenic diabetes insipidus were diagnosed at the age of 3 months to 10 years. Symptoms appeared within the first few weeks of life. The diagnosis was confirmed by polyuria, low urinary osmolality (97-225 mosm/kg H20), hypernatraemia (max. 171 mmol/l) and the missing response to vasopressin. The treatment was variable; 4 boys received only hydrochlorothiazide (2-2.5 mg/kg/d) which lead to a reduction of the daily urinary volume of 26-44%. Hyperelectrolytaemia disappeared and a normal thriving could be achieved. Later an additional treatment with indomethacin (2 mg/kg/d) was necessary in 3 boys because of an increase of polyuria; there was a further reduction of the daily urinary volume of 50-60%. The combination of hydrochlorothiazide and indomethacin in the treatment of the congenital nephrogenic diabetes insipidus was well tolerated and seems to be--especially during the first few years of life--a necessary and effective treatment which allows a normal thriving and psychointellectual development.     

Hyponatraemia and hypovolemic shock with tuberculous meningitis

A 12-year-old boy with tuberculous meningitis and hydrocephalous, after undergoing revision of ventriculo-peritoneal shunt had persistent impairment of sensorium and episodes of hyponatremia (serum sodium 104 to 125 mmol/l), accompanied by polyuria, signs of poor peripheral, perfusion hypotension and low CVP, and high urinary sodium excretion (114–60 mmol/ I). A diagnosis of cerebral salt wasting syndrome (CSWS) was made and was treated with saline replacement and fludrocortisone (10 μg/kg/day). Within next 3 days the sensorium, signs of shock, urine output and serum and urinary sodium returned to normal. The case illustrates that life-threatening hyponatremia in a child with neurological illness could be caused by CSWS, which must be differentiated from Syndrome of inappropriate antidiuretic hormone secretion (SIADH), as CSWS requires rigorous salt and volume replacement in contrast to fluid restriction in SIADH.     

The significance of renal prostaglandins for kidney function in early childhood

When comparing iatrogenic inhibition with endogenous stimulation of renal prostaglandin production, the role of this mediator and modulator system for renal function becomes apparent. Renal perfusion and glomerular filtration as well as modulation of tubular function with respect to electrolyte and water excretion is significantly influenced by renal prostaglandin activity. Treatment with the prostaglandin cyclooxygenase inhibitor indomethacin reduces the endogenous creatinine clearance by about fifty percent in a state of a diminished circulatory blood volume, such as may exist during left-to-right shunting across a persistent ductus arteriosus in preterm infants. In addition, urinary electrolyte and water excretion is reduced by increased tubular absorption leading to marked oliguria. In contrast, electrolytes and water are lost in congenital renal tubular disorders associated with increased prostaglandin E2 (PGE2) activity (a so called hyperprostaglandin E syndrome). Patients with this renal disorder require a permanent high dosed indomethacin therapy. After this pharmacotherapy has brought electrolyte and water metabolism into balance, no deterioration of glomerular filtration and renal perfusion was observed. This is in accordance with the general principle that renal function only becomes dependent on the vasodilatory activity of renal prostaglandins in a stress situation resulting in the threat of hypoperfusion. It is essential to bear in mind the physiological and pathophysiological role of renal prostaglandins, when prescribing frequently administered prostaglandin cyclooxygenase inhibitors like aspirin, paracetamol or indomethacin in pediatrics. Otherwise, renal function may deteriorate or the kidney will be irreversibly damaged.     

Effect of a modified fluid therapy on renal function during indomethacin therapy for persistent ductus arteriosus

A rehydration with 7 ml/kg/h for six hours prior to indomethacin administration prevented the adverse effects of this drug on renal function in prematures with persistent ductus arteriosus. During the 36 hour observation period after indomethacin administration, no significant changes in serum creatinine, sodium, and potassium concentrations, or urinary flow, creatinine clearance, or filtered sodium could be detected. The only significant finding was a reduction in fractional sodium excretion. One can assume that this beneficial effect of the fluid load is due to a suppression of some parts of the vasoconstrictor mechanisms, which are responsible for the deterioration of renal function in newborns during indomethacin therapy. Using this modified fluid regimen, no cardiovascular side effects were noticed, a closure of the duct was achieved in 7 of 10 treatment courses.     

Effect of a Modified Fluid Therapy on Renal Function during Indomethacin Therapy for Persistent Ductus Arteriosus

A rehydration with 7 ml/kg/h for six hours prior to indomethacin administration prevented the adverse effects of this drug on renal function in prematures with persistent ductus arteriosus. During the 36 hour observation period after indomethacin administration, no significant changes in serum creatinine, sodium, and potassium concentrations, or urinary flow, creatinine clearance, or filtered sodium could be detected. The only significant finding was a reduction in fractional sodium excretion. One can assume that this beneficial effect of the fluid load is due to a suppression of some parts of the vasoconstrictor mechanisms, which are responsible for the deterioration of renal function in newborns during indomethacin therapy. Using this modified fluid regimen, no cardiovascular side effects were noticed, a closure of the duct was achieved in 7 of 10 treatment courses.     

Bartter syndrome in two siblings--antenatal and neonatal observations

Bartter syndrome was diagnosed in two siblings born to healthy unrelated parents. Each pregnancy was complicated by severe polyhydramnios. The first child was treated with indomethacin from the age of then weeks on. At the age of six years he is doing very well: height is 109.9 cm (P3) and weight 17.8 (P3). Studies of the amniotic fluid during the mother's second pregnancy showed high chloride concentrations (112, 117, and 119 mEq/l), normal levels of sodium, potassium, calcium and creatinine and low prostaglandin E2 (5.0-22.3 pg/ml) and F2 alpha (36-71.7 pg/ml) concentrations. Severe chloride and sodium wasting after birth resulted in hypochloremia, hyponatremia and dehydration. Concomitantly an immediate and striking increase in urinary PGE2 excretion from 45 to 1022 pg/ml was observed. Indomethacin therapy had to be stopped after one week when necrotising enterocolitis developed.     

Mechanism of action of indomethacin in tubular defects

Indomethacin, a potent prostaglandin synthesis inhibitor, has been proven to be effective in a number of tubular defects characterized by enhanced prostaglandin (namely, prostaglandin E2 (PGE2) production, but its mechanism of action is poorly understood. To elucidate further the mechanism(s) by which indomethacin reverses the abnormal tubular functions, five children with different tubular defects (nephrogenic diabetes insipidus, three cases; Fanconi syndrome, one case; and pseudohypoaldosteronism, one case) were treated with indomethacin. Indomethacin, 1 mg/kg every eight hours, was given for 1 week to all children and then was given chronically to four of the children who responded to the drug. Its use was suspended in a 10 year-old-boy with nephrogenic diabetes insipidus because it proved ineffective. To assess the site along the nephron where indomethacin affects the solute and water excretion, an acute water load study was performed in three responsive children before and during the treatment. Indomethacin did not significantly alter the glomerular filtration rate but was effective in reducing diuresis and levels of urinary sodium and potassium excretion. In the child with Fanconi syndrome, indomethacin was also effective in controlling the urinary loss of phosphate, urate, glucose, and bicarbonate. Results of the water load studies show that indomethacin decreases the delivery of solute from the proximal tubule, reduces the fractional free water clearance, and increases the urine-plasma osmolar ratio.(ABSTRACT TRUNCATED AT 250 WORDS)     

Successful indomethacin treatment of two paediatric patients with severe tubulopathies. A boy with an unusual hypercalciuria and a girl with cystinosis.

Two children were followed for severe congenital tubulopathies: a boy presented an excessive sodium, calcium and water excretion; a girl had cystinosis and a De Toni-Debré-Fanconi syndrome. These renal defects were both associated with increased levels of plasma renin activity and aldosterone, and excessive urinary PGE1 production. They had been unresponsive to therapeutic attempts. Only indomethacin treatment was successful in reversing the biochemical abnormalities and improving the growth pattern.     

SERUM INDOMETHAC1N CONCENTRATIONS AFTER INTRAVENOUS ADMINISTRATION TO PRETERM INFANTS WITH PATENT DUCTUS ARTERIOSUS

Abstract. Petersen, S., Christensen, N. C, Jensen, K. M. and Ryssing, E. (Departments of Neonatology and Paediatrics, Rigshospitalet, Copenhagen, and Dumex Ltd., Copenhagen, Denmark). Serum indomethacin concentrations after intravenous administration to preterm infants with patent ductus arteriosus. Acta Paediatr Scand, 70:729,.–Six preterm infants with PDA received 14 treatments with indomethacin 0.2 mg/kg intravenously. Auscultatory and echocardiographic assessment indicated closure of the duct in 2, partial closure in 2, and no effect in 2 infants. The mean serum concentration of indomethacin was: 15 min after the first injection 1314 ng/ml, after 1 hour 970 ng/ml, after 6 hours 718 ng/ml, and after 24 hours 388 ng/ml. The mean half-life of indomethacin in the serum was 20 hours (range 9–50 hours). Side effects in all infants were hyponatraemia, decreased urinary output, decreased urinary sodium excretion, and weight gain. One infant had transient thrombocytopenia and gastrointestinal haemorrhage. By intravenous administration of indomethacin in a dose of 0.2 mg/kg to preterm infants a sufficiently high serum concentration is obtained shortly after the injection. To maintain a high serum concentration for a longer period it is recommended to give a second dose of 0.2 mg/kg after 6 hours and if necessary a third dose of 0.1 mg/kg 24 hours after the first dose.     

Relationship between maturity, electrolyte balance and the function of the renin-angiotensin-aldosterone system in newborn infants.

Simultaneous measurement of plasma renin activity (PRA), plasma aldosterone concentration (PA) and urinary aldosterone excretion (UAE) was made using the RIA method along with determination of Na and K balance in 1-week-old neonates with gestational age of 30-41 weeks (mean 35.9 weeks) and birth weight of 1,160-4,670 g (mean 2,680 g). It was demonstrated that PRA decreased from the value of 36.3 +/- 6.3 ng/ml/h (mean +/- SE) to a level of 10.2 +/- 2.1 ng/ml/h (p less than 0.001), PA did not change and UAE increased from 3.3 +/- 0.8 to 7.8 +/- 1.4 microgram/day (p less than 0.01) as the gestational age advanced from 30-32 to 39-41 weeks. There was no correlation between either PRA and PA and UAE. PRA showed a significant positive correlation with urinary Na excretion (p less than 0.001) and plasma K concentration (p less than 0.05), but it was negatively related to Na balance (p less than 0.001). Significant negative correlations were found between UAE and urinary Na excretion (p less than 0.05), urinary Na/K ratio (p less than 0.01 (and plasma K concentration (p less than 0.05); however, UAE positively correlated with Na balance (p less than 0.01). It is concluded that, in response to renal salt wasting and to the subsequent negative salt balance, premature infants can augment their PRA above values found for full-term infants. Their adrenals, however, failed to respond adequately to this stimulation.     

Increased renal biosynthesis of prostaglandin E2 and thromboxane B2 in human congenital obstructive uropathy

Animal experiments have shown that after ureter obstruction hydronephrotic kidneys release increased amounts of prostaglandin E2 (PGE2) and thromboxane A2 (TxA2), suggesting that these prostanoids modify renal blood flow and excretory function in this model. To test the hypothesis that these mechanisms are also operative in congenital obstructive uropathy, we measured prostanoid excretion rates in 12 neonates and infants with congenital unilateral or bilateral hydronephrosis. Prostanoid determinations were performed by gas chromatography mass spectrometry. PGE2 and thromboxane B2 (TxB2) (non-enzymatic metabolite of TxA2) excretion exceeded the normal range in eight and 11 of 12 patients, respectively. Median PGE2 excretion was 22, range 4-572 ng/h/1.73 m2 (normal 3-16). Median TxB2 excretion was 22, range 3-188 ng/h/1.73 m2 (normal 3-7). No other renal prostanoids (prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha) or systemic prostanoid metabolites (PGE-M, 2,3-dinorthromboxane B2, 11-dehydro-thromboxane B2, 2,3-dinor-6-keto-prostaglandin F1 alpha) were consistently elevated. A second group of 12 neonates with congenital obstructive uropathy was followed sequentially. PGE2 and thromboxane B2 excretion rates increased even further after surgical decompression and gradually normalized during follow-up. There was a significant relationship between elevated FeNa and enhanced PGE2 and TxB2 excretion. These data suggest that endogenous renal formation of PGE2 and TxA2 is selectively stimulated in hydronephrotic kidneys in neonates and infants. PGE2 and TxA2 may be involved in modulating renal function in these infants.     

High efficacy and minor renal effects of indomethacin treatment during individualized fluid intake in premature infants with patent ductus arteriosus

AIM: To determine the efficacy and the renal side effects of indomethacin treatment for closure of a patent ductus arteriosus (PDA) in premature infants during an individualized fluid regime that avoids hypovolaemia and subsequent prostaglandin-dependent renal perfusion. METHODS: Observational retrospective analysis of the efficacy of indomethacin in premature infants with PDA treated in a single institution from June 1992 to May 2000. The clinical course and renal effects were analysed in the subgroup of infants born from June 1995 to May 2000. The management of infants at risk and the treatment of infants with PDA followed a standardized protocol that included echocardiographic screening for PDA, indomethacin treatment before congestive failure develops (early symptomatic treatment) and an individualized fluid intake. RESULTS: In total, 412 infants with a gestational age < or = 32 wk were identified. Fifty-six infants with a PDA (14%) were treated with indomethacin [mean birthweight 936 (95% confidence interval 866-1006) g; gestational age 27.3 (26.8-27.9) wk]. Indomethacin treatment was successful in 52 infants (93%). The clinical course and renal effects were analysed in 41 infants. Most infants received three indomethacin doses of 0.2 mg kg(-1) every 12 h. Urine output transiently decreased from 5.6 (4.6-6.4) to 4.6 (3.9-5.3) ml kg(-1) (h(-1). Serum creatinine temporarily increased from 0.90 (0.83-0.98) to 1.06 (0.87-1.24)mg dl(-1). Fluid intake was 158 (148-168) ml kg(-1) d(-1) before indomethacin and decreased to 142 (131-154) ml kg(-1) d(-1). CONCLUSION: Indomethacin is very effective for closure of a PDA, even in very premature infants, and is not associated with clinically significant renal side effects.     

The renal hemodynamic effects of ibuprofen in the newborn rabbit

In early childhood, nonsteroidal anti-inflammatory drugs are mainly used to either prevent or treat premature labor of the mother and patent ductus arteriosus of the newborn infant. The most frequently used prostaglandin-synthesis inhibitor is indomethacin. Fetuses exposed to indomethacin in utero have been born with renal developmental defects, and in both the unborn child and the term and premature newborn this drug may compromise renal glomerular function. The latter has in the past also been observed when i.v. indomethacin or i.v. acetylsalicylic acid (aspirin) were administered to newborn rabbits. The present experiments were designed to evaluate whether ibuprofen has less renal side effects than indomethacin, as claimed. Three groups of anesthetized, ventilated, normoxemic neonatal rabbits were infused with increasing doses of ibuprofen (0.02, 0.2, 2.0 mg/kg body weight) and the following renal parameters were measured: urine volume, urinary sodium excretion, GFR, and renal plasma flow. Renal blood flow, filtration fraction, and the renal vascular resistance were calculated according to standard formulae. Intravenous ibuprofen caused a dose-dependent, significant reduction in urine volume, GFR, and renal blood flow with a fall in filtration fraction in the animals receiving the highest dose of ibuprofen (2 mg/kg body weight). There was a very steep rise in renal vascular resistance. Urinary sodium excretion decreased. These experiments in neonatal rabbits clearly show that acute i.v. doses of ibuprofen also have significant renal hemodynamic and functional side effects, not less than seen previously with indomethacin.     

Renal hemodynamics and functional changes during the transition from fetal to newborn life in sheep

The effects of delivery on renal function and renal hemodynamics were studied in conscious and chronically instrumented fetal sheep. Each fetus was studied 1 h before delivery and 1, 4, and 24 h following delivery by cesarean section. Delivery was not associated with significant changes in plasma renin activity, plasma angiotensin II, plasma aldosterone, and plasma arginine vasopressin concentrations when determined 1 h after birth. On the other hand, the transition from fetal to newborn life was accompanied by significant increases in plasma epinephrine and norepinephrine concentrations. No significant changes in renal blood flow velocity or in renal vascular resistance were observed during the transition from fetal to newborn life; percent changes in renal blood flow velocity and renal vascular resistance values were respectively 15.4 +/- 11 and -2.4 +/- 1.0% at 1 h, 4.0 +/- 8.0 and 5.8 +/- 9.1% at 4 h, and 3.2 +/- 8.0 and 9.7 +/- 13% at 24 h. No significant changes in urinary flow rate, urine osmolality, free water clearance, and osmolar clearance were observed in the first 24 h following delivery. On the other hand, glomerular filtration rate increased 3-fold from 3.3 +/- 0.4 ml/min in fetuses to 10.1 +/- 1.2 ml/min in newborn lambs at 24 h of age. This rise in glomerular filtration rate was associated with significant decreases in urinary sodium excretion (UNaV) (from 36 +/- 7 to 13 +/- 3 microEq/min) and fractional excretion of sodium (FENa) (from 7.6 +/- 0.9 to 1.1 +/- 0.3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Parathyroid hormone and calcitonin secretion in uraemic infants

In six infants aged between 4 and 8 months with chronic renal failure, we have studied blood levels of calcium (Ca), phosphorus (P), alkaline phosphatase, immunoreactive parathyroid hormone (PTH), and calcitonin (CT), as well as urinary excretion of Ca, P, hydroxyproline and cyclic AMP under basal conditions and during an infusion of 20 mg/kg of 10% Ca gluconate in normal saline over 4 h.Under basal conditions four infants had normal serum Ca and P values, alkaline phosphatase levels at the upper limit of normal, and very high PTH (range: 1450–2550 pg Eq/ml) and CT (range: 700–1900 pg/ml) levels. The urinary Ca excretion was low, whereas the urinary excretion of P, hydroxyproline and cyclic AMP was high. During Ca infusion, the total serum Ca and CT levels increased, PTH fell without however reaching the normal upper limit, and urinary P and cyclic AMP excretion decreased. In two infants with osteodystrophy and the highest levels of PTH (2900 and 3500 pg Eq/ml respectively) there was no suppression of PTH during Ca infusion.     

Renal effects of cyclooxygenase-2 inhibition in fetal lambs

We used late gestation fetal lambs to examine the effects of a selective COX-2 inhibitor (celecoxib) on fetal renal function. After a 2-hour baseline period, each fetus was exposed to either saline (control, n = 10), 'low-dose' celecoxib (plasma concentration 0.47 microg/ml, n = 4), or 'high-dose' celecoxib (1.4 microg/ml, n = 8) during a 5-hour study period. High-dose celecoxib (but not low-dose celecoxib) caused a significant decrease in urine volume, free water clearance, arterial pH, and an increase in blood lactate compared with the control group. There were no significant differences in creatinine clearance, fractional excretion of sodium and potassium, or in renal blood flow between the 3 groups. These effects are similar to those reported for the nonselective COX-1/-2 inhibitor, indomethacin. COX-2 appears to play an important role in promoting free water excretion in the fetal lamb.     

The effect of metoclopramide administration on electrolyte status and activity of renin-angiotensin-aldosterone system in premature infants

The present study has been carried out to define whether endogenous dopamine contributes to the regulation of renal sodium handling and the function of the renin-angiotensin-aldosterone system in low birth weight premature infants. Twelve premature infants with mean birth weight of 1420 g and mean gestational age of 29.2 wk were given metoclopramide (MTC) in a dose of 0.1 mg/kg/day to treat delayed gastric emptying, regurgitation, and abdominal distension at the age of 17-23 days. Infants were kept on either a low (2-3 mEq/kg/day) or high (4-7 mEq/kg/day) sodium diet to modulate activity of RAAS. Prior to and after a 3-day period of MTC administration, blood samples were taken, and in six male infants 24-h urine collections were made to determine plasma and urine electrolytes, plasma renin activity, plasma aldosterone concentration, and urinary aldosterone excretion. We demonstrated that plasma sodium and potassium concentrations and plasma renin activity were not altered by MTC. On the other hand, in response to MTC, there was a significant increase in urinary sodium excretion (1.8 +/- 0.3 versus 2.3 +/- 0.3 mEq/kg/day) and a decrease in potassium excretion (1.2 +/- 0.2 versus 0.8 +/- 0.1 mEq/kg/day); plasma aldosterone concentration and urinary aldosterone excretion decreased significantly from initial values of 2101 +/- 274 pg/ml and 2.91 +/- 0.52 micrograms/day to 1500 +/- 207 pg/ml (p less than 0.01) and 2.21 +/- 0.43 micrograms/day (p less than 0.01), respectively, after MTC. These alterations were independent of the pretreatment hormone levels.(ABSTRACT TRUNCATED AT 250 WORDS)