BIOCHEMICAL CORRECTION IN THE SYNDROME OF HYPERTENSION AND HYPERKALAEMIA BY SEVERE DIETARY SALT RESTRICTION SUGGESTS RENIN-ALDOSTERONE SUPPRESSION CRITICAL IN PATHOPHYSIOLOGY

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.     

Is spironolactone safe for dialysis patients?

BACKGROUND: Spironolactone is useful in heart failure, but is not given to dialysis patients for fear of hyperkalaemia. This study evaluated the safety of spironolactone administration in haemodialysis patients. METHODS: Fifteen haemodialysis outpatients with mean serum potassium <5.6 mEq/l over the preceding 4 months were treated with spironolactone 25 mg daily for 28 days. Serum potassium was measured before every haemodialysis during the study. Aldosterone and renin were measured at the beginning and end of the study. Patients were monitored for side effects. Data were examined with a paired t-test, with patients serving as their own controls and P < 0.05 considered significant. A sample size of 14 was required to achieve a power of 0.8 and a P = 0.05 to detect a potassium difference of 0.5 +/- 0.6 mEq/l. All patients were analysed as intention-to-treat. RESULTS: The mean potassium level was 4.6 +/- 0.6 mEq/l at baseline and 4.9 +/- 0.9 mEq/l at study completion (P = 0.14). Thirteen patients completed the trial with no potassium levels >6.0 mEq/l. Four patients had potassium levels between 5.5 and 6.0 mEq/l. One patient was withdrawn at day 20 after developing hyperkalaemia (7.6 mEq/l). Another patient was withdrawn at day 25 after missing a dialysis treatment. There were no differences in either baseline or 28 day aldosterone or renin levels (16.8 +/- 28.8 vs 11.7 +/- 6.1 ng/dl and 3.5 +/- 3.9 vs 3.5 +/- 3.5 ng/ml/h, respectively). Infrequent side effects included dry mouth, nosebleed, pruritis, gynecomastia and diarrhoea. No significant leukopenia or anaemia was noted. CONCLUSIONS: Spironolactone may be considered as a treatment option for selected chronic haemodialysis patients with heart disease.     

OACE inhibition does not interfere with acute extrarenal or renal potassium disposal in chronic renal failure

The influence of angiotensin converting enzyme (ACE) inhibition on acute extrarenal and renal potassium elimination in stable chronic renal failure has been examined in 10 male patients median age 44 y; mean CL_CR 42 ml·min^–1·1.73 m^–2. In a double blind, placebo-controlled cross-over study, K⁺ 0.3 or 0.4 mmol·kg^–1 body weight was infused IV on two occasions while the patients also received an infusion either of placebo or 0.5 mg of the ACE inhibitor perindoprilat in random order. Plasma K⁺ levels and urinary K⁺ excretion were measured at regular intervals. During the study patients adhered to an isocaloric diet providing a standardised daily intake of potassium and sodium (50 mmol K⁺ and 40 mmol Na⁺).The median rise in plasma K⁺ was not significantly different after placebo ( K 0.66 mmol·1^–1) compared with to the infusion of perindoprilat ( K 0.66 mmol·1^–1). The median baseline urinary K⁺ excretion rate was 6.5 mmol·3 h^–1 before the placebo infusion and 5.9 mmol·3 h^–1 before infusion of perindoprilat. During the potassium load, the urinary excretion rate rose to 16.1 mmol·3 h^–1 (after placebo) and 15.1 mmol·3 h^–1 after perindoprilat in the first 3 h, and it returned almost to the baseline value within the next 3 h (5.6 mmol·3 h^–1 after placebo and 5.7 mmol·3 h^–1 after perindoprilat); the differences were not statistically significant.With perindoprilat a decrease in mean arterial blood pressure and ACE activity, an increase in renin plasma activity and a decrease in aldosterone concentrations were observed compared to the placebo infusion. There was no significant differences plasma in adrenaline or insulin levels after either infusion.Thus, ACE inhibition did not interfere either with the extrarenal or the renal disposal of an acute potassium load in patients with chronic renal failure.     

Diuretic-related hypokalaemia: the role of diuretics,potassium supplements,glucocorticoids and β2-adrenoceptor agonists

All 5,047 consecutive inpatients admitted to the Internal Medicine Division of a teaching hospital (Zieglerspital, Berne) between 1982 and 1985 were registered in accordance with the CHDM (Comprehensive Hospital Drug Monitoring) questionnaire of adverse drug reactions (ADRs). Of them, 2,439 were treated with at least one potassium losing diuretic. The hospital records of the patients were reviewed with particular regard to serum potassium levels, and on the basis of this evaluation, the patients were assigned to four different diuretic treatment groups, and the incidence of hypokalaemia related to diuretic treatment was estimated. The overall rate of occurrence of hypokalaemia was 21.1% at a serum potassium level <3.5 mmol·1^–1, and 3.8% <3.0 mmol·1^–1. Hypokalaemia of less than 3.5 mml·1^–1 developed 24.9% (217/870) of patients treated with potassium losing diuretics alone; in 19.7% (101/513) treated with potassium losing diuretics in conjunction with potassium substitution, in 15.1% (66/438) treated with a combination of diuretics (potassium losing with potassium sparing), and in 20.0% (12/60) treated with combined diuretics and potassium substitution. Only the differences between the first and the two subsequent groups were statistically significant. The overall incidence of hypokalaemia below 3.0+mmol·1^–1 was significantly lower in the patients on combined diuretics without potassium substitution than in the patients on potassium losing diuretics with potassium substitution.Oral or parenteral administration of glucocorticoids (prednisone 5 to 2,000 mg/d) was a significant risk factor for hypokalaemic events. ₂-Adrenoceptor agonists had not effect. The patient's age, sex, renal function and numbers of drugs received were evaluated in a multivariate analysis, in order to take into account their influence on the risk of developing hypokalaemia. The number of drugs above 12 (and, less importantly, female sex) was the main risk factor for this ADR.The comparison between hypokalaemia and hyperkalaemia in this group of inpatients showed the significance of reduced renal function in the occurrence of hyperkalaemia.     

Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism

The aim of this prospective, randomised, open-label, blinded-end point study was to compare the efficacy and safety of eplerenone versus spironolactone in patients with bilateral idiopathic hyperaldosteronism (IHA). After a 2-week washout period, 34 patients with IHA were assigned to receive either spironolactone 25 mg b.i.d. (n = 17) or eplerenone 25 mg b.i.d. (n = 17) for 24 weeks. If the patients' blood pressure (BP) was not < 140/90 mmHg, the doses were gradually increased up to 400 mg for spironolactone and 200 mg for eplerenone. If the patients' BP remained uncontrolled, a daily dose of hydrochlorothiazide 12.5 mg was added at week 16. The primary outcome was the percentage of patients with BP < 140/90 mmHg at 16 weeks (i.e., with aldosterone antagonist monotherapy). The patients' BP was normalised in 13 out of 17 (76.5%) and 14 out of 17 (82.4%) patients in the spironolactone and eplerenone groups, respectively (p = 1.00). Systolic BP decreased more rapidly with eplerenone. Serum potassium levels were normalised (> 3.5 mmol/l) in all patients at 4 weeks. Mild hyperkalaemia was observed in two patients receiving 400 mg of spironolactone and in three patients receiving 150 mg of eplerenone. Two patients presented with bilateral painful gynaecomastia at the end of week 16 while receiving 400 mg of spironolactone. Switching spironolactone to 150 mg of eplerenone daily resulted in resolution of gynaecomastia and also maintained BP control. At the end of the study, 19 patients were on eplerenone and 15 were on spironolactone. However, this did not affect the primary end point, because the switch from spironolactone to eplerenone (in two patients) occurred at the end of week 16. It was concluded that eplerenone was as effective as spironolactone in reducing BP in patients with IHA. The risk of mild hyperkalaemia was similar with both drugs.     

Sodium and Potassium in Red Blood Cells of Premature Infants during the First Few Days: Risk of Hyperkalaemia

ABSTRACT. Erythrocyte sodium and potassium were studied in 64 newborn infants including 21 very low birthweight infants (birthweight < 1500 g) during the first three days after birth. Erythrocyte sodium showed a positive correlation with gestational age ( r =0.63, p <0.01) and birthweight ( r =0.66, p <0.01). Erythrocyte potassium was negatively correlated with birthweight ( r = -0.33, p <0.05). The Na/K ratio in red blood cells showed a positive correlation with gestational age ( r =0.60, p <0.01) and birthweight ( r =0.65, p <0.01). In VLBW infants plasma potassium rose significantly ( p <0.01) from 0–6 h to 12–30 h and decreased from 12–30 h to 30–60 h ( p <0.05). Erythrocyte potassium decreased slightly from 0–6 h to 12–30 h, but not significantly. A new finding that "more immature infants have higher potassium and lower sodium concentration in RBC" may suggest a potential risk of hyperkalaemia in tiny infants.     

Paramethoxyamphetamine (PMA) poisoning; a 'party drug' with lethal effects

Among young people in Norway the recreational use of amphetamine derivatives seems to be increasing. Methylenedioxymethamphetamine (MDMA), known as ecstasy, is the dominant substance, having both stimulant and psychedelic properties. Depending on the illegal source of these so-called 'party drugs' the content and purity can vary. This case report describes the first lethal case of paramethoxyamphetamine (PMA) and paramethoxymethamphetamine (PMMA) intoxication reported in Norway. A 16-year-old male was admitted to a local hospital in a coma with seizures and hyperthermia after he had been found undressed and barefooted in a local forest (temperature 2 degrees C). He was intubated and given supportive care. Blood chemistry revealed hypoglycaemia, hypocalcaemia and hyperkalaemia. Shortly after transfer to the central hospital he developed bradycardia with continuous seizures and asystole. Adverse effects of MDMA are well described and include serotonergic and sympathomimetic symptoms with hyperthermia, coagulopathy, rhabdomyolysis and acute kidney and liver failure. Case reports of PMA deaths collectively suggest PMA to be more toxic than MDMA. A delayed effect after intake of PMA compared with MDMA can lead to increased intake. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. Increased thermo genesis will result in a search for cooling, which explains the attempt to undress and a desire to submerge in water. In a cool climate this behaviour itself can be lethal. Measures to treat seizures, hypoglycaemia, electrolyte anomalies and hyperthermia are the therapeutic goals. No specific treatment is available.     

Hypokalaemia and hyperkalaemia

Disturbances in potassium homoeostasis presenting as low or high serum potassium are common, especially among hospitalised patients. Given the fact that untreated hypokalaemia or hyperkalaemia is associated with high morbidity and mortality, it is critical to recognise and treat these disorders promptly. In this article, normal potassium homoeostasis is reviewed initially and then a pathophysiological approach to work-up and management of hypokalaemia and hyperkalaemia is presented. Recent advances with respect to the role of kidney in handling of the potassium, the regulation of renal ion transporters in hypokalaemia, and treatment of hypokalaemia and hyperkalaemia will be discussed.