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Chronic splanchnic hemodynamic effects of spironolactone with unrestricted sodium diet in patients with compensated cirrhosis.

The purpose of this study is to determine the hemodynamic effects of spironolactone administration associated with an unrestricted sodium diet (salt 10 g) in patients with compensated cirrhosis and portal hypertension. We studied the hemodynamic changes following eight weeks of administration of either placebo (N = 6) or spironolactone (100 mg/day) (N = 6 Pugh-Child's A and 6 B). No significant changes were observed after the administration of the placebo. Spironolactone induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-10.1 +/- 13.3%, P < 0.05), which was associated with a significant reduction of cardiac output (-11.5 +/- 9.3%, P < 0.01), plasma volume (-8.1 +/- 4.7%, P < 0.01), and wedged hepatic venous pressure (-10.5 +/- 11.6%, P < 0.05). There was no significant change in hepatic blood flow and there was no significant correlation between the change in the HVPG and the change in circulating plasma volume. A decrease in the HVPG greater than 10% was observed in eight of 12 patients (67%), defined as responders, at eight weeks. Six of six (100%) grade A patients and two of six (33%) grade B patients responded. This study demonstrated that spironolactone with an unrestricted sodium diet decreased the HVPG in grade A patients but did not significantly decrease the HVPG in grade B patients.

Diuretics↗

Cholestyramine and spironolactone and their combination in digitoxin elimination.

The effects of oral cholestyramine 4 gm 8 times daily and spironolactone 300 mg daily, given independently and in combination, on the elimination rate of digitoxin were studied in 6 healthy subjects pretreated with 0.1 or 0.15 mg oral digitoxin daily for 30 days before each intervention. The mean pretreatment digitoxin concentrations for the group ranged from 21 +/- 2.9 (SD) ng/ml to 28.5 +/- 6.9 ng/ml. The mean control digitoxin half-life (t 1/2) was reduced from 141.6 to 84.4 by treatment with cholestyramine alone. Treatment with spironolactone alone prolonged the mean digitoxin t 1/2 to 192.2 hr. The mean digitoxin t 1/2 after both active drugs was intermediate at 102.9 hr. Spironolactone did not fulfill the expectation from animal studies that it would enhance the clearance of digitoxin by cholestyramine. The prolongation of digitoxin elimination after spironolactone may contraindicate this drug in digitoxin intoxication.

Canrenone↗

Dose-response relationships for spironolactone in combination with a potassium-wasting diuretic.

The plasma and urine electrolyte responses to repeated doses of spironolactone, 25, 50, and 100 mg, in combination with metolazone, 2.5, 5.0, and 10 mg, were examined in 18 healthy subjects (six at each dose of metolazone). During the period of pharmacologic steady state, there were log linear spironolactone dose-response relationships for plasma potassium, sodium, and bicarbonate (P less than 0.001 in each case) with no contraindication to parallelism between the metolazone groups. In the absence of mineralocorticoid challenge, spironolactone dose-urine electrolyte responses could not be demonstrated. However, after fludrocortisone, spironolactone log dose-response trends were linear with respect to natriuresis (P = 0.027), antikaliuresis (P = 0.020), and log 10 Na/K (P = 0.001), which is usually considered the best single index of renal antimineralocorticoid activity, and exhibited parallelism between the metolazone doses. These observations suggest that a convenient bioassay for aldosterone antagonists in normal men may be provided by the electrolyte responses to repeated doses of such drugs in combination with potassium-wasting diuretics. In view of the limitations of other methods, this approach may have particular relevance to the evaluation of potassium-sparing properties.

Adult↗

Pulmonary function and electrolyte balance following spironolactone treatment in preterm infants with chronic lung disease: a double-blind, placebo-controlled, randomized trial.

OBJECTIVE: To study the effect of spironolactone on dietary electrolyte supplementation, pulmonary function, and electrolyte balance in premature infants with chronic lung disease. STUDY DESIGN: A double-blind, randomized, and placebo-controlled trial was designed to study two groups of low birth weight infants with chronic lung disease at Pennsylvania Hospital. The placebo group received chlorothiazide and a placebo, and the spironolactone group received chlorothiazide and spironolactone during the 2-week study period. A two-tailed t-test was used to determine equivalence between the two groups. RESULTS: Pulmonary compliance, resistance and tidal volume, serum sodium and potassium, and FIO2, were not statistically different between the two groups. The need for sodium and/or potassium chloride did not differ between the two groups, nor did the quantity of each salt. CONCLUSION: The addition of spironolactone did not reduce the requirement for supplemental electrolytes, nor did it improve pulmonary mechanics or electrolyte balance.

Chronic Disease↗

Influence of spironolactone on endogenous steroid metabolism in man.

1. Mild secondary hyperaldosteronism was induced in ten healthy young males by a low sodium diet for 14 days. After 7 days on the diet, five subjects each were treated with spironolactone (group S) or triamterene (group T) daily. 2. The daily negative sodium balance was identical during the first 3 days of medication with both drugs but sodium loss was more severe during the following days in group S. Consequently, the plasma renin activity was higher during the last days of spironolactone compared with triamterene medication. 3. Changes in plasma electrolytes were similar in both groups. 4. No influence of either drug on the synthesis chain leading to cortisol was observed. 5. Plasma concentrations of deoxycorticosterone and corticosterone, however, increased considerably in group S, whereas triamterene did not influence these steroids. 6. Whereas triamterene induced a prompt increase of plasma aldosterone, an increase was delayed for the first 3 days of treatment with spironolactone. Later, plasma aldosterone concentrations rose rapidly in group S and were no longer different from those in group T. 7. Results are interpreted as being due to an initial inhibition of aldosterone synthesis by spironolactone, which is finally compensated, at least in part, by increased activation of the renin-angiotensin system.

Adrenal Cortex Hormones↗

Therapeutic benefit of spironolactone in experimental chronic cyclosporine A nephrotoxicity.

BACKGROUND: Cyclosporine A (CsA) is an immunosuppressive drug used to prevent tissue allograft rejection. However, its long-term utilization is limited due to chronic nephrotoxicity for which no prevention is available. This study evaluated the effect of spironolactone on renal functional and structural alterations induced by CsA, and assessed whether the protective effect was associated with a reduction of transforming growth factor-beta (TGF-beta) and the change of extracellular matrix protein mRNA level. METHODS: Male Wistar rats fed with low sodium diet were divided in four treatment groups: vehicle, CsA (30 mg/kg), spironolactone (20 mg/kg), or CsA+spironolactone. After 21 days, creatinine clearance (CCr), blood CsA, arteriolopathy in renal tissue, and TGF-beta, collagen I, collagen IV, fibronectin, and epidermal growth factor (EGF) mRNA levels in renal cortex were determined. RESULTS: CsA reduced the CCr and up-regulated TGF-beta, collagen I and fibronectin mRNA expression with a significant development of arteriolopathy, and reduced EGF mRNA levels. In contrast, spironolactone administration prevented the fall in renal function and TGF-beta, collagen I, and fibronectin up-regulation, together with a reduction of arteriolopathy and tubulointerstitial fibrosis. CONCLUSION: Our data show that aldosterone plays an important role as a mediator of renal injury induced by CsA. Thus, mineralocorticoid receptor blockade may be a potential strategy to prevent CsA nephrotoxicity.

Aldosterone↗

Nadolol plus spironolactone in the prophylaxis of first variceal bleed in nonascitic cirrhotic patients: A preliminary study.

Treatment with beta-blockers fails to decrease portal pressure in nearly 40% of cirrhotic patients. Recent studies have suggested that treatment with spironolactone reduces pressure and flow in the portal and variceal systems. This trial was designed to assess if nadolol plus spironolactone is more effective than nadolol alone to prevent the first variceal bleeding. One hundred patients with medium and large varices who had never bled and were without ascites were included in a prospective, randomized, multicenter, double-blind, placebo-controlled trial. The patients were randomized into 2 groups: 51 received nadolol plus placebo (N + P) and 49 received nadolol plus spironolactone 100 mg/d (N + S). Hepatic venous pressure gradient (HVPG) and activity of the renin-aldosterone system (plasma renin activity/plasma aldosterone levels) were measured in 24 patients. There were no significant differences in the appearance of variceal bleeding and ascites between groups at a mean follow-up of 22 +/- 16 months. However, analyzing both complications together, the incidence was significantly higher in the N + P group than in the N + S group (39% vs. 20%; P <.04). Clinical ascites was also higher in patients in the N + P group than in the N + S group (21% vs. 6%; P <.04). Significant increases in plasma renin activity and plasma aldosterone levels were only observed in patients in the N + S group (P <.01). The cumulative probabilities of remaining free of bleeding and ascites were similar in both groups after 70 months of follow-up. In conclusion, these results suggest that nadolol plus spironolactone does not increase the efficacy of nadolol alone in the prophylaxis of the first variceal bleeding. However, when bleeding and ascites were considered together, the combined therapy effectively reduced the incidence of both portal-hypertensive complications.

Adrenergic beta-Antagonists↗

[Serum hormones before and during therapy with cyproterone acetate and spironolactone in patients with androgenization].

The effect of cyproterone acetate (CPA) and spironolactone (SPL) on the serum androgen concentrations of premenopausal women with symptoms of hyperandrogenism were investigated in a total of 39 women. The observation period was 12 months. CPA was administered according to the Hammerstein regimen: cyproterone acetate (CPA) [Androcur] 100 mg/die 5.-14. day of the cycle; ethinylestradiol (EE) [Progynon C]: 40 mg/die 5.-25. day of the cycle; Spironolactone (SPL) was given in a dosage of 100 mg/die from day 1.-21. of the cycle. During the therapy with CPA a significant decrease of total testosterone (61%), free testosterone (78%), LH (48%) and 17 alpha-Hydroxyprogesterone (72%) was observed; during the medication with spironolacton only a significant decrease of 5 alpha-dihydrotestosterone (81%), which could not be seen during CPA use, was observed. Serum concentrations of total testosterone, free testosterone, LH and 17 alpha-Hydroxyprogesterone remained unchanged. DHA and DHAS did not change during neither medication. Since peripheral androgens were not suppressed by SPL the positive therapeutical effect of SPL can be explained by the antiandrogenic effect at the level of the receptor. A disadvantage of spironolacton is the lack of contraceptive efficacy. In cases where contraindication for oral contraceptives are present SPL can be considered as a good alternative to CPA. The suppressive effect of CPA/EE on total testosterone, LH addition to the antivulatory effect makes it the preferable medication for hyperandrogenemic patients with polycystic changes of the ovaries (PCOD).

Adult↗

[Effect of dexamethasone and spironolactone therapy in calcium and phosphate homeostasis in premature infants with a birth weight under 1,500 g].

BACKGROUND: Dexamethasone and spironolactone are widely used in the management of bronchopulmonary dysplasia in premature infants. There are few data available about adverse effects of this drugs on the urinary excretion of calcium and phosphate in this group of patients. PATIENTS: 24 h-urine samples could be collected in 85 infants between 8 and 40 days. 31 infants received dexamethasone and 32 spironolactone. METHODS: Multivariate variance analysis was performed to study the influence of dexamethasone and spironolactone on the measured excretion of calcium and phosphate. The influence of gestational and postnatal age, calcium and phosphate intake and theophylline treatment were excluded by use as covariates. RESULTS: Spironolactone showed no significant influence on the urinary excretion of calcium or phosphate. Dexamethasone treatment increased the daily excretion of phosphate in the urine and decreased the phosphate concentration in serum. CONCLUSION: None of the examined drugs showed a significant increase of the renal excretion of calcium in preterm infants. Thus a higher risk of nephrocalcinosis development due to these drugs has not been confirmed. Dexamethasone treatment might increase the risk of osteopenia by enhancing phosphate excretion.

Bronchopulmonary Dysplasia↗

Drug-induced eosinophilia and multisystemic failure with positive patch-test reaction to spironolactone: DRESS syndrome.

We report the case of a 58-year-old man who suffered from a generalized and intolerable itching one month after starting treatment with colchicine, amiodarone, perindopril, allopurinol and spironolactone. From the start of treatment he had progressively developed erythroderma, fever, anorexia and prostration, oedema of both hands and face, hypereosinophilia (42%; 5810 eosinophils/mm3), hepatic failure (including cholestatic jaundice, cytolysis, coagulation abnormalities and hypoproteinaemia), exocrine pancreatic failure (with severe steatorrhoea), renal failure, metabolic acidosis, aggravation of pre-existing cardiac insufficiency and oedema of the lower extremities. All medications were stopped and the condition improved slowly until complete remission was reached 4 months later. Patch-testing was performed, including the various drugs. All the tests (including components of the vehicles) were negative, except for spironolactone, which gave a strong positive reaction. Ten controls in healthy volunteers were negative. The diagnosis of drug rash with eosinophilia and systemic symptoms (DRESS) induced by spironolactone was made. This is the first report of DRESS due to spironolactone.

Drug Eruptions↗

High serum prostate-specific antigen concentrations in hirsute women do not decrease with treatment by the combination of spironolactone and the contraceptive pill.

Using an ultrasensitive assay, prostate-specific antigen (PSA) has been detected in female serum and has been proposed as a potential marker of androgen excess in hirsute women. Measurement of PSA levels in serum may play a role in monitoring hirsutism during antiandrogen therapy. We investigated the role of PSA as a marker of androgen activity in hirsute patients taking spironolactone together with oral contraceptive pills containing ethinyl estradiol and gestodene. Twenty-eight hirsute patients were included in the study. Clinical and biochemical variables including serum levels of PSA (using an ultrasensitive chemiluminscent immunoassay), dehydroepiandrosterone sulfate, total testosterone, free testosterone and 17-hydroxyprogesterone concentrations were recorded at baseline and after six cycles of treatment. Fifteen healthy women were included in the study as controls. Serum PSA levels in hirsute women were clearly higher than in the control group (0.023 +/- 0.004 vs. 0.006 +/- 0.003 ng/ml, p < 0.001) and correlated with baseline serum free testosterone concentrations (r = 0.518, p = 0.005). After 6 months, serum PSA concentrations as compared with baseline values did not change significantly in patients who were given spironolactone plus contraceptive pills (p = 0.4) despite a marked decrease in total testosterone, free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and hirsutism score (p < 0.05). Thus, serum PSA levels in hirsute women were higher than in non-hirsute healthy controls. A 6-month course of treatment with spironolactone combined with contraceptive pills containing ethinylestradiol and gestodene did not reduce high serum PSA levels in these subjects. In conclusion, the serum PSA level is not a convenient biochemical marker with the available assays for the management of hirsute women treated with the combination of spironolactone and oral contraceptives.

17-alpha-Hydroxyprogesterone↗

Influence of spironolactone on cadmium-induced changes in hepatic and renal gluconeogenic enzymes in rats.

Serum glucose, serum protein, serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), and hepatic and renal gluconeogenic enzymes [pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-diphosphatase (F-1,6-DPase), and glucose-6-phosphatase (G-6-Pase)] were determined in rats treated daily with cadmium alone (0.25 mg/kg X d, injected ip and in rats pretreated with spironolactone (50 mg/kg x d and 100 mg/kg X d, injected sc) prior to cadmium administration. Rats receiving no treatment, propylene glycol, or spironolactone (100 mg/kg X d, injected sc) were used as controls. The daily treatments were continued for an extended period of 90 d, and the rats were sacrificed at 30-, 60-, and 90-d intervals during the continuous daily treatment schedule. Cadmium treatment significantly increased the amount of serum protein, glucose, serum enzymes, and all the four key gluconeogenic enzymes as compared to controls. Pretreatment of rats with spironolactone 6 h prior to cadmium injection daily antagonized the cadmium effect of the above parameters. It appears from these results that spironolactone reduces the effects of cadmium on the key gluconeogenic enzymes in rat kidney and liver.

Animals↗

Nanosuspension formulations for low-soluble drugs: pharmacokinetic evaluation using spironolactone as model compound.

Various particle sizes of spironolactone as a model low solubility drug were formulated to yield micro-and nanosuspensions of the type solid lipid nanoparticles and DissoCubes. Seven oral and one i.v. formulations were tested in an in vivo pharmacokinetic study in rats with the aim of characterizing the bioavailability of spironolactone on the basis of its metabolites canrenone and 7-alpha-thiomethylspirolactone. In addition, a dose escalation study was carried out using nonmicronized spironolactone suspension as well as a nanosuspension type DissoCubes. On the basis of AUC as well as Cmax ratios, three groups of formulations were distinguished. The biggest improvement was seen with a solid lipid nanoparticle formulation yielding a 5.7-fold increase in AUC for canrenone and a similar improvement based on the Cmax metric, followed by a group of three formulations containing nanosized, micronized, and coarse drug material and surfactant. The DissoCubes nanosuspension yielded highly significant improvements in bioavailability averaging 3.3-fold in AUC and 3.0-fold in terms of Cmax for canrenone. The third class encompasses all other formulations, which showed very little to no improvement in bioavailability. The results show that the particle size minimization was not the major determining factor in the bioavailability improvement. Rather, the type of surfactant used as stabilizer in the formulations was of greater importance. Improvement in drug solubility in the intestine as well as in dissolution rate of spironolactone are the most likely mechanisms responsible for the observed effect, although additional mechanisms such as permeability enhancement may also be involved.

Administration, Oral↗

Time-related changes in plasma adrenal steroids during treatment with spironolactone in primary aldosteronism.

Time-related changes in plasma levels of aldosterone, deoxycorticosterone, corticosterone, and cortisol were studied during treatment with spironolactone in 8 patients with primary aldosteronism due to adenomas. Plasma renin activity (PRA), serum sodium and serum potassium were also measured. The patients were treated with spironolactone, 75 to 225 mg daily, and blood samples were withdrawn on days 7, 14, and 21 to 28 of drug administration. Plasma aldosterone concentrations (PAC) were not altered by spironolactone; however, significant increases were observed in plasma deoxycorticosterone on days 21 to 28 and in plasma corticosterone and cortisol on days 14 and 21 to 28. The suppressed PRA values were markedly increased on days 21 to 28 and low levels of serum potassium returned to the normal range on day 7. The lack of increase in PAC, despite a remarkable rise in PRA and serum potassium, suggests biosynthetic inhibition of spironolactone at the sites of 18-hydroxylation and/or 18-oxidation, because of the elevation of deoxycorticosterone and corticosterone.

Adenoma↗

Spironolactone, early acute eGFR changes, and clinical outcomes in patients with heart failure with preserved ejection fraction: insights from TOPCAT Americas.

AIMS: Early acute changes in estimated glomerular filtration rate (eGFR) have been well described with renin-angiotensin system inhibitors and sodium-glucose cotransporter-2 inhibitors, but less is known about the frequency, prognostic relevance, and implications of these changes after mineralocorticoid receptor antagonist (MRA) initiation in patients with heart failure with preserved ejection fraction (HFpEF). METHODS: We performed a post-hoc analysis of 1648 patients enrolled in the TOPCAT trial (Americas regional subgroup), defining an early eGFR dip as a &#x2265;15% decrease in eGFR between baseline and week 4. Landmark analyses assessed the association of eGFR changes, treatment, and the primary composite endpoint (cardiovascular death, HF hospitalization, or aborted cardiac arrest). RESULTS: Within 4 weeks of treatment initiation, 431 (26%) patients experienced acute eGFR decrease with a higher proportion of patients assigned to spironolactone [269 (33%)] compared with placebo [162 (20%)] (odds ratio 1.97; 95% confidence interval 1.58-2.47). An acute eGFR decrease was independently associated with higher risk of subsequent cardiovascular outcomes, irrespective of treatment arm. However, treatment with spironolactone appeared beneficial in reducing the primary cardiovascular outcome irrespective of the presence [hazard ratio 0.75 (0.53-1.08)] or absence [0.80 (0.64-1.00)] of early eGFR decrease (Pinteraction = .81). At any given magnitude of eGFR decline, risk of the primary endpoint was consistently lower with spironolactone compared with placebo (Pinteraction = .64). CONCLUSIONS: Early acute eGFR changes were common and adversely prognostic in patients with HFpEF. Spironolactone treatment was beneficial in improving cardiovascular outcomes, despite a modest increase in the likelihood of acute eGFR decrease. An acute eGFR decrease early after MRA initiation should not automatically prompt treatment discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00094302.

Humans↗

Spironolactone improves lung diffusion in chronic heart failure.

AIMS: To evaluate whether anti-aldosteronic treatment influences lung diffusion (DLCO) in chronic heart failure (HF) patients. Spironolactone improves clinical conditions and prognosis in chronic HF and reduces connective tissue matrix turnover; DLCO abnormalities in chronic HF are related to increase in fibrosis and connective tissue derangement. METHODS AND RESULTS: Thirty stable chronic HF patients, with reduced DLCO (<80% of predicted), were randomly assigned to active treatment (25 mg spironolactone daily) or placebo in addition to conventional anti-failure treatment. They were evaluated by quality of life questionnaire, laboratory investigations, cardiopulmonary exercise test, and pulmonary function test, which included DLCO and membrane diffusing capacity (DM). The evaluation was done before treatment and 6 months after. Quality of life score and standard pulmonary function tests were not significantly affected by spironolactone, while active treatment increased DLCO due to an increase of DM (DLCO: 18.3+/-3.9 vs. 19.9+/-5.5 mL/min/mmHg; DM: 28.1+/-7.7 vs. 33.3+/-8.6 mL/min/mmHg) and peak oxygen consumption (peak VO2 16.8+/-1.9 vs.18.6+/-2.2 mL/min/kg). Increments of DLCO and peak VO2 were linearly related (R=0.849, P<0.001). CONCLUSION: These data show a positive effect of spironolactone on gas diffusion and exercise capacity suggesting a novel mechanism by which anti-aldosteronic drugs improve HF clinical condition and prognosis.

Exercise Test↗

Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction.

AIMS: Congestive heart failure (CHF) is associated with severe structural changes of atria, contributing to impaired atrial function and the risk of arrhythmia. This study investigated the effects of CHF treatments on atrial remodelling. METHODS AND RESULTS: Three months after myocardial infarction (MI), rats were treated for 1 month with spironolactone, lisinopril, or atenolol alone or in combination. Echocardiography-Doppler tissue imaging, haemodynamic measurements, and 24-h Holter monitoring were used to characterize the cardiomyopathy. Atrial fibrosis was quantified with Picrosirius Red staining. Left atrial diameter was increased (5.8+/-0.6 mm in MI vs. 3.6+/-0.3 mm in sham; P<0.0001), as was atrial fibrosis (26.7+/-3.8% in MI vs. 10.5+/-2.2% in sham; P<0.0001), which correlated with left ventricular (LV) dysfunction after 3 months of MI. P-wave duration was also increased and premature atrial beats were frequent on the 24-h electrocardiogram. Similar improvements in LV dysfunction were observed after 1 month of spironolactone, ACE-inhibitor, or beta-blocker therapy alone or in combination. Atrial hyperexcitability was reduced by all the treatments, but only spironolactone attenuated atrial fibrosis and reduced P-wave duration. CONCLUSION: Atrial fibrosis caused by chronic CHF is reduced by spironolactone.

Animals↗

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, pruritus, 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.

Adult↗