atrial-natriuretic-factor and Hyperkalemia

A 56-year-old white female presented with longstanding hyperkalemia, hyperchloremia, and hypertension. Renal function was normal. Plasma renin levels were low as were serum and urinary aldosterone. Plasma cortisol levels were normal. Fludrocortisone was ineffective in lowering serum potassium. Plasma renin and aldosterone levels responded appropriately to salt restriction and to postural changes. Plasma atrial natriuretic hormone (ANH) and urinary prostaglandins (PG) were normal. Salt loading resulted in suppression of renin and aldosterone levels and stimulation of plasma ANH and urinary PG but failed to increase potassium or chloride excretion. The persistent hyperkalemia, hyperchloremia, and suppressed renin-aldosterone axis were consistent with type II pseudohypoaldosteronism. Hydrochlorothiazide was effective in normalizing serum potassium levels and blood pressure. These studies exclude abnormalities in ANH and PG secretion in this disorder and are compatible with an abnormality in chloride reabsorption.

Topics: Aldosterone; Atrial Natriuretic Factor; Female; Humans; Hyperkalemia; Hypertension; Middle Aged; Potassium; Prostaglandins; Pseudohypoaldosteronism; Renin

Thirty-four patients (65.3+/-3.3 years of age, mean+/-SEM) with hyperkalemia (serum potassium >5.0 mEq/L) had measurement of their renin-aldosterone system. Nineteen patients (56%) had plasma renin activity (PRA) >1.5 ng/mL/h, which was not low, while 15 (44%) had PRA <1.5. Twelve of the 15 hyporeninemic hyperkalemic patients were studied to determine whether their renin-aldosterone system responded to 2 weeks of furosemide, 20 mg daily. Four were nonresponders: PRA averaged 0.3+/-0.1 ng/mL/h, and it did not increase with furosemide or respond to captopril before or after furosemide. Eight patients were responders: PRA averaged 0.6+/-0.2 ng/mL/h and increased with furosemide to 5.5+/-3.4 ng/mL/h. Captopril failed to increase PRA before furosemide, but PRA increased to 15.3+/-8.4 ng/mL/h after furosemide. Plasma aldosterone was low in both nonresponders and responders (3.5+/-1.2 ng/dL vs 5.8+/-2.5 ng/dL) and did not increase significantly with furosemide (4.3+/-1.7 ng/dL vs 8.7+/-2.5 ng/dL). Serum potassium did not fall and therefore did not limit the rise in aldosterone. Renin responders had greater body weight, were predominantly female (6/8 vs 2/4) and were more likely to have diabetes mellitus (7/8 vs 0/4). Plasma atrial natriuretic peptide (ANP) fell with furosemide in 8 of 8 responders and in 1 of the 2 nonresponders in whom it was measured. Neither group had suppressed plasma prorenin levels, indicating no suppression of renin gene expression. These results indicate that many hyperkalemic patients do not have suppressed PRA. Further, a majority of patients with suppressed PRA have high levels of ANP and can respond to diuretic therapy with a rise in PRA and a fall in ANP, suggesting physiologic suppression of the renin system by volume expansion. A minority of hyperkalemic patients with suppressed PRA had PRA that did not increase under these study conditions.

Topics: Adult; Aged; Aged, 80 and over; Aldosterone; Antihypertensive Agents; Atrial Natriuretic Factor; Captopril; Diuretics; Enzyme Precursors; Female; Furosemide; Humans; Hyperkalemia; Male; Middle Aged; Renin; Treatment Outcome

Acute hyponatremia, following neurosurgery, results from inappropriate antidiuretic hormone secretion (SIADH) or cerebral salt wasting (CSW). CSW is due to abnormally high atrial or brain natriuretic peptides (ANP, BNP), which block all stimulators of zona glomerulosa steroidogenesis, resulting in mineralocorticoid deficiency. A 3 year-old girl presented CSW at day 4, after resection of craniopharyngioma and hypophysectomy. Hyponatremia, hyperkalemia and high natriuresis occurred on day 8, with low renin and aldosterone and elevated BNP 120.3 ng/ml (undetectable before surgery). Fludrocortisone 100 microg/day controlled natriuresis and restored electrolytes within 24 hours. A 5 year-old boy presented CSW at day 6 after partial resection of optic glioma. Fludocortisone 100 microg/day restored electrolytes within 8 hours. ANP was elevated, 60.6 ng/l, aldosterone and renin were low. Fludrocortisone supplementation should be considered in CSW, as excessive natriuresis is controlled, and electrolytes are easily restored, avoiding life-threatening complications of this complex disorder.

Topics: Atrial Natriuretic Factor; Cerebrum; Child; Child, Preschool; Craniopharyngioma; Electrolytes; Female; Fludrocortisone; Humans; Hyperkalemia; Hyponatremia; Hypophysectomy; Male; Mineralocorticoids; Natriuretic Peptide, Brain; Pituitary Neoplasms; Postoperative Complications; Postoperative Period; Sodium Chloride

Elderly patients with hyperkalaemia often have low concentrations of plasma renin and aldosterone, perhaps secondary to reduced glomerular filtration and sympathetic insufficiency. The endocrine response to surgical stress and volume expansion during anaesthesia was studied in seven elderly patients with hyperkalaemia (mean age 87.7 +/- SD 5.3 years), 18 elderly patients without hyperkalaemia (86.5 +/- 5.5 years), and 18 younger patients (52.6 +/- 7.2 years) as controls. Base-line values, in hyperkalaemic elderly patients, for plasma renin activity and plasma aldosterone concentration were 0.8 +/- 0.3 ng mL-1 h-1 and 2.8 +/- 0.8 pg mL-1 respectively (significantly lower than in the younger patients), and 287 +/- 42 pg mL-1 for plasma atrial natriuretic peptide levels, which were significantly higher. The plasma renin activity and aldosterone concentrations in elderly patients with hyperkalaemia were at all times lower, but not significantly, than those of the elderly patients without hyperkalaemia. The atrial natriuretic peptide concentrations (351 +/- 48 pg mL-1) in the hyperkalaemic elderly were significantly higher 90 min after induction of anaesthesia than in the normokalaemic elderly (108 +/- 38 pg mL-1). Hormone concentrations in the hyperkalaemic patients did not change during anaesthesia, but plasma atrial natriuretic peptide concentrations increased significantly in the normokalaemic elderly, and plasma renin activity and aldosterone of the younger patients increased significantly during anaesthesia. These results indicate that plasma renin activity, and the concentrations of aldosterone and of atrial natriuretic peptide in elderly patients with hyperkalaemia are unresponsive to surgical stress and volume expansion.

Topics: Adult; Aged; Aged, 80 and over; Aging; Aldosterone; Anesthesia, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Atrial Natriuretic Factor; Femoral Neck Fractures; Follow-Up Studies; Glomerular Filtration Rate; Humans; Hyperkalemia; Isoflurane; Middle Aged; Nitrous Oxide; Plasma Substitutes; Potassium; Renal Insufficiency; Renin; Sodium; Stress, Physiological; Thiopental

Atrial natriuretic peptide (ANP) has been shown to suppress aldosterone secretion under certain circumstances, although the physiological significance of this is uncertain. We wondered if ANP would suppress potassium-stimulated aldosterone secretion in man and, if so, whether we might find high circulating levels of ANP in patients with the syndrome of acquired hypoaldosteronism. We studied seven healthy young subjects under two conditions: 1) infusion of KCl (0.5 mmol/kg) over 45 min, and 2) KCl infused with ANP (0.01 microgram/kg.min) for 60 min. We also evaluated ANP levels in eight elderly subjects with the syndrome of acquired hypoaldosteronism, as defined by hyperkalemia (mean serum K+, 5.3 +/- 0.1 mmol/L) associated with inappropriately low aldosterone levels (216 +/- 50 pmol/L). In the normal subjects, ANP almost completely suppressed the aldosterone response to KCl infusion (P less than 0.001, by analysis of variance) despite a similar rise in the serum potassium level with KCl alone (0.70 +/- 0.07 mmol/L) and KCl plus ANP (0.75 +/- 0.09 mmol/L). PRA fell slightly during KCl plus ANP treatment, but did not change during the infusion of KCl alone. ANP levels were approximately 800 pmol/L during the ANP infusion studies. Endogenous ANP levels in the hyperkalemic patients with hypoaldosteronism were markedly elevated at 1186 +/- 340 pmol/L (compared to 93 +/- 10 pmol/L in healthy elderly controls), a level that would be capable of suppressing the potassium-mediated aldosterone response. Exogenous infusion of ANP suppressed the aldosterone response to hyperkalemia, and ANP levels were found to be markedly elevated in a group of patients with hyperkalemia and hypoaldosteronism. We suggest that ANP may contribute to clinically significant hypoaldosteronism and hyperkalemia in the syndrome of acquired hypoaldosteronism.

Topics: Adult; Aldosterone; Atrial Natriuretic Factor; Humans; Hyperkalemia; Hypoaldosteronism; Infusions, Intravenous; Male; Potassium

To test the hypothesis that renal sensitivity to atrial natriuretic peptide (ANP) is impaired in Gordon's syndrome (hypertension and hyperkalaemia with normal glomerular filtration rate) we infused alpha-hANP into two patients with this syndrome (a sister and a brother, 19 and 18 years of age). For comparison, 11 healthy volunteers were also examined. The infusion of alpha-hANP increased urinary volume and excretion of sodium similarly in the patients and controls. The excretion of potassium did not change in either the patients or the controls. The infusion of alpha-hANP had no effect on the serum potassium levels or the plasma CO2 content in the patients. The present results do not confirm the hypothesis of lack of sensitivity to ANP as a pathophysiological concept in Gordon's syndrome.

Topics: Adolescent; Adult; Atrial Natriuretic Factor; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney; Male; Middle Aged; Potassium; Sodium

The hormonal regulation of sodium and volume homeostasis was investigated in three patients (two related) with the syndrome of familial hyperkalemic acidosis and hypertension with normal glomerular filtration rate. Recumbent plasma renin activity was low during normal sodium intake (135 mmol daily), and the response to upright posture or to low sodium diet (10 mmol daily) was blunted. Recumbent plasma aldosterone levels were normal in two patients and high in one, and the standing values were elevated in one; responses to upright posture were brisk on low sodium diet. Angiotensin II infusion induced a marked increase in plasma aldosterone. Plasma atrial natriuretic peptide was at the upper limit of normal during normal sodium intake, decreased during diuretic therapy, and increased during sodium chloride infusion in one patient. Basal urinary prostaglandin E2, prostaglandin F2 alpha, and 6-ketoprostaglandin F1 alpha excretion rates were decreased, and thromboxane B2 was increased. Total blood and plasma volumes were subnormal, whereas extracellular fluid volume and exchangeable sodium values were close to or above (in one patient) the mean normal values. Chronic treatment with hydrochlorothiazide in two patients corrected the hyperkalemic acidosis and hypertension, but on its discontinuation (in one patient) all biochemical abnormalities promptly reappeared.

Topics: Adult; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Family; Female; Humans; Hydrochlorothiazide; Hyperkalemia; Hypertension; Male; Pedigree; Syndrome

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.

Topics: Absorption; Adult; Aldosterone; Atrial Natriuretic Factor; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney Tubules, Proximal; Lithium; Male; Metabolic Clearance Rate; Potassium; Renin; Sodium; Syndrome

Gordon's syndrome was diagnosed in a 19-year-old woman who had hypertension, hyperkalemia and hyperchloremic acidosis. In family screening, hyperkalemia and hyperchloremic acidosis were also found in the patient's mother and brother. The proband and her brother were studied and showed normal glomerular function with normal renal sodium conservation and urine acidification mechanisms. The levels of plasma aldosterone were normal in both subjects. The renin activity was low in the proband but normal in the brother. Both the basal and the volume-stimulated plasma concentration of atrial natriuretic peptide was low in the two patients. As compared with controls, the kaliuretic response to infusion of sodium chloride was not decreased in the patients. Hydrochlorothiazide promptly corrected the acidosis and the hyperkalemia as well as normalized the raised blood pressure of the proband. We suggest that a deficiency of atrial natriuretic peptide rather than an unusual avidity for sodium chloride reabsorption by the renal tubules plays a significant pathogenetic role in Gordon's syndrome.

Topics: Acid-Base Equilibrium; Adolescent; Adult; Atrial Natriuretic Factor; Female; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Male; Renin-Angiotensin System; Sodium Chloride; Syndrome

We present the case of a 14-year-old boy who had secondary hyperkalemic periodic paralysis caused by Gordon's syndrome. This syndrome consists of hypertension, tubular acidosis, and hyperkalemia with normal glomerular filtration rate. The pathophysiological mechanism is still unknown. Pathophysiological studies suggest that in this disorder the kidney lacks sensitivity to atrial natriuretic peptide. After treatment with hydrochlorothiazide, serum potassium and plasma aldosterone values, plasma renin activity, and blood pressure became normal and the attacks of periodic paralysis disappeared.

Topics: Adolescent; Atrial Natriuretic Factor; Humans; Hydrochlorothiazide; Hyperkalemia; Hypertension; Male; Paralysis; Syndrome

Basic examination of Mr S., 45 years of age, short in stature and overweight (1.60 m, 76 kg), was carried out because of the mild hypertension (mean AP 125 mm Hg) from which he had suffered for 20 years. The results were as follows: (1) variable hyperkalemia: plasma potassium values were 5.3 to 6.9 mmol/l; (2) normal renal function: serum creatinine 91.5 mumol/l, clearance of inulin 136.6 ml/mn; (3) proximal tubular acidosis: plasma bicarbonate and chloride values were 18.4 and 109 mmol/l, respectively; urinary pH was 7.1 with negative H+ ions urinary excretion (-33 mumol/mn); when plasma bicarbonate level was raised to 26 mmol/l by acute loading, fractional excretion of bicarbonate increased to 19,5 p. 100 while plasma potassium value decreased to 4.2 mmol/l; (4) low PRA (0.29 ng/ml/h) and normal plasma aldosterone concentration (63 pg/ml) with a normal intake of sodium and in a recumbent position. Plasma atrial natriuretic factor (ANF) level was normal: 14 fmol/ml. Intravenous infusion of ANF for 2 h (1 microgram/mn) induced the expected increases in urinary flow rate, and sodium and potassium excretions (+226, +307 and +171 p. 100, respectively). Intravenous infusion of isotonic saline (2 l in 2 h) and oral administration of fludrocortisone acetate for 4 weeks (400 micrograms per day) resulted in a normal decrease in PRA and plasma aldosterone concentration, a normal rise in plasma ANF level (22 and 42 fmol/ml) while slightly increasing AP without improving bicarbonaturia and acidosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acidosis, Renal Tubular; Aldosterone; Atrial Natriuretic Factor; Humans; Hyperkalemia; Hypertension; Kidney; Male; Middle Aged; Pseudohypoaldosteronism; Renal Tubular Transport, Inborn Errors; Renin; Syndrome

A family with the syndrome of hypertension and hyperkalaemia affecting six members in two generations is reported from Australia, where the first two sporadic cases were described. All family members had hyperkalaemia, hyperchloraemia and normal creatinine clearance. Only one affected adult and no affected children were hypertensive, possibly because of habitual low-salt diets. Plasma potassium fell significantly during fludrocortisone acetate administration, and urine potassium increased during saline infusion, consistent with renal tubular responsiveness to mineralocorticoid. Low plasma renin activity and pressor hyper-responsiveness to angiotensin II suggested sodium volume overload, but atrial natriuretic factor (ANF) was normal or only slightly elevated when compared with clearly elevated levels in primary aldosteronism. Plasma ANF was unresponsive to the usually reliable stimulus of angiotensin infusion in the two brothers affected and to saline infusion in one of them. These findings are consistent with a renal tubular avidity for sodium, leading to volume expansion, suppression of renin, and, depending on dietary sodium intake, hypertension. A role for dysregulation of ANF in the pathophysiology is possible.

Topics: Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Australia; Fludrocortisone; Humans; Hyperkalemia; Hypertension; Pedigree; Renin; Syndrome

A 14-year-old boy with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome) is described. The patient's clinical symptoms consisted of periodic paralysis, slight metabolic acidosis of the proximal type and hypercalciuria. Prostaglandin excretion was normal. Infusion of atrial natriuretic peptide had no effect on electrolyte excretion or glomerular function although a normal increase in cyclic guanosine monophosphate was demonstrated in plasma and urine. This lack of sensitivity to atrial natriuretic peptide offers a new pathophysiological concept in this syndrome. Treatment with hydrochlorothiazide was successful in this case.

Topics: Adolescent; Atrial Natriuretic Factor; Glomerular Filtration Rate; Humans; Hyperkalemia; Hypertension; Kidney Glomerulus; Male; Paralysis; Syndrome

Topics: Acidosis; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Female; Humans; Hyperkalemia; Hyponatremia; Hypotension; Middle Aged; Oligopeptides; Renin; Teprotide

Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone-producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid-suppressible hyperaldosteronism. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition. responsiveness in this condition. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.

Topics: Adult; Atrial Natriuretic Factor; Bartter Syndrome; Humans; Hyperaldosteronism; Hyperkalemia; Hypertension; Male; Middle Aged; Plasma Volume; Syndrome