Introduction: Gitelman Syndrome (GS), a rare autosomal recessive inherited disorder, is frequently unrecognized in the clinical setting. GS typically manifests with severe hypokalemia with debilitating and potentially fatal consequences if untreated. As of writing, confirmatory genetic assays are currently unavailable in the country, and the diagnosis of GS is primarily based on several biochemical laboratory tests. This results in the difficulty with prompt diagnosis of GS in the locality. Case: We present a 52-year-old male who came in with chronic, intermittent paraparesis associated with persistent hypokalemia. A diagnosis of GS was made biochemically based on renal wasting of potassium and magnesium, hypocalciuria, and metabolic alkalosis. Electrolyte correction with lifelong supplementation, and administration of Spironolactone resulted in the resolution of bilateral leg weakness. Electrolyte levels were maintained within normal limits in the outpatient setting. Conclusion GS is an uncommon potentially debilitating disorder that may lead to problematic, potentially fatal consequences to electrolyte abnormalities if left untreated. The lack of awareness and consequent delay in the diagnosis, and the unavailability of confirmatory genetic testing remains a clinical challenge. Timely recognition and initiation of treatment leads to early control of electrolyte levels, and better prognosis.
Gitelman&rsquo ; s Syndrome ; Paraparesis ; Hypokalemia ; Hypomagnesemia ; Spironolactone ; Case Report

BACKGROUND: The efficacy of combined diuretic treatment in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. METHODS: In a single-center, double-blinded, randomized controlled trial, we randomly assigned 51 adult CAPD patients to receive furosemide 1,000 mg/day, hydrochlorothiazide 100 mg/day, and spironolactone 50 mg/day (triple diuretics [TD] group) or furosemide 1,000 mg/day plus placebo (single diuretic [SD] group) for 6 months. The primary outcome was the difference in daily urine output at the 3rd and 6th month of the study compared to baseline (ΔUO) between the SD and TD group. Secondary outcomes were urinary sodium (UNa) and potassium (UK) excretion and overhydration (OH) measured by bioimpedance at 3 and 6 months compared to baseline (ΔUNa, ΔUK, and ΔOH, respectively) and daily glucose exposure (g/day). RESULTS: Forty-three of 51 patients completed the 6-month trial. The ΔUO at 3 and 6 months was significantly higher in the TD group compared to the SD group (386.32 ± 733.92 mL/day vs. −136.25 ± 629.08 mL/day, P < 0.001, at 3 months; 311.58 ± 640.31 mL/day vs. 120.00 ± 624.07 mL/day, P < 0.001, at 6 months) but there was no significant difference in ΔUNa and ΔUK excretion. Hydration status was significantly better in the TD group (ΔOH 1.84 ± 2.27 L vs. 0.44 ± 1.62 L, P = 0.03, at 3 months; 1.49 ± 2.82 L vs. −0.48 ± 2.61 L, P = 0.02, at 6 months). There was no serious adverse event in this study. CONCLUSION: For end-stage renal disease patients on CAPD, the combination of furosemide, hydrochlorothiazide, and spironolactone results in higher urine output and better volume control compared to furosemide alone.
Adult ; Diuretics ; Furosemide ; Glucose ; Humans ; Hydrochlorothiazide ; Kidney Failure, Chronic ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory ; Potassium ; Sodium ; Spironolactone

BACKGROUND: Previous studies have shown that aldosterone antagonists have a proteinuria-lowering effect in patients with proteinuria and progressive proteinuric disease not adequately controlled by the use of angiotensin receptor blockers (ARBs). Aldosterone antagonists, in combination with ARBs, might improve proteinuria in patients with glomerulonephritis (GN). METHODS: In the present retrospective study, we evaluated the proteinuria-lowering effect and drug safety of low-dose spironolactone (12.5 mg/day) in 42 patients with GN being treated with an ARB. RESULTS: Proteinuria decreased from a mean total-protein-to-creatinine (TP/Cr) ratio of 592.3 ± 42.0 mg/g at baseline to 335.6 ± 43.3 mg/g after three months of treatment with spironolactone (P < 0.001). After the initial three months, the mean TP/Cr ratio increased progressively at six, nine, and 12 months; however, it was still less than the baseline value (P = 0.001, < 0.001, and < 0.001, respectively). Although serum Cr levels increased significantly at three and nine months compared with baseline (P = 0.036 and 0.026, respectively), there was no time effect of treatment (P = 0.071). Serum potassium levels tended to increase with time (P = 0.118), whereas systolic and diastolic blood pressures decreased with time (P = 0.122 and 0.044, respectively). CONCLUSION: Low-dose spironolactone in combination with an ARB reduced proteinuria in patients with GN, which could represent a novel treatment option in individuals whose proteinuria is not optimally controlled by the use of ARBs alone.
Angiotensin Receptor Antagonists ; Angiotensins* ; Glomerulonephritis* ; Humans ; Mineralocorticoid Receptor Antagonists ; Potassium ; Proteinuria ; Retrospective Studies ; Spironolactone*

Introduction: Resistant hypertension (RH) is defined as a blood pressure (BP) reading that remains above goal despite concurrent use of three optimally dosed antihypertensives of different classes, including a diuretic. Spironolactone, a mineralocorticoid receptor antagonist, has shown significant benefit in reduction of BP in recent trials and is used empirically as an add-on therapy for RH. The researchers’ objective is to evaluate the BP-lowering efficacy of spironolactone in patients with resistant hypertension. Methods: A meta-analysis was performed on randomized controlled trials (RCTs) comparing office or home BP reduction using spironolactone with placebo or an alternative drug regimen on top of standard-triple drug therapy among patients with RH. The study was conducted in reference to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Five RCTs were included comprising a total of 662 patients. Three of these studies were found to have low risk of bias while two had unclear risk of bias. Compared to placebo, the addition of spironolactone significantly decreased office systolic BP (weighted mean difference [WMD]= -16.33, 95% confidence interval [CI]=-24.68 to -7.97, P=0.0001) and office diastolic BP (WMD=-6.12, 95% CI= -9.35 to -2.89, P=0.0002). Compared to an alternative drug regimen, additional spironolactone resulted in a significantly greater reduction in office systolic BP (WMD=-4.58mmHg, 95% CI=-7.19, -1.97, P= 0.0006) and home systolic BP (WMD= -4.33, 95% CI= 5.55, -3.12, P< 0.00001); while the addition of spironolactone had no significant difference compared to an alternative drug regimen in reducing office diastolic BP (WMD=-3.35, 95% CI=-12.08 to +5.38, P=0.45) and home diastolic BP (WMD= 0.00, 95 % CI=-0.73 to 0.73, P=1.0). Conclusion Spironolactone, when added to triple-drug anti-hypertensive therapy, showed significant reduction of systolic office and home BP. It should be considered as the add-on medication of choice for BP reduction in patients with RH.
Antihypertensive Agents ; Spironolactone ; Blood Pressure

Emerging evidence indicates that aldosterone and mineralocorticoid receptors (MRs) are associated with the pathogenesis of erectile dysfunction. However, the molecular mechanisms remain largely unknown. In this study, freshly isolated penile corpus cavernosum tissue from rats was treated with aldosterone, with or without MRs inhibitors. Nuclear factor (NF)-kappa B (NF-κB) activity was evaluated by real-time quantitative PCR, luciferase assay, and immunoblot. The results demonstrated that mRNA levels of the NF-κB target genes, including inhibitor of NF-κB alpha (IκB-α), NF-κB1, tumor necrosis factor-alpha (TNF-α), and interleukin 6 (IL-6), were higher after aldosterone treatment. Accordingly, phosphorylation of p65/RelA, IκB-α, and inhibitor of NF-κB kinase-β was markedly increased by aldosterone. Furthermore, knockdown of MRs prevented activation of the NF-κB canonical pathway by aldosterone. Consistent with this finding, ectopic overexpression of MRs enhanced the transcriptional activation of NF-κB by aldosterone. More importantly, the MRs antagonist, spironolactone blocked aldosterone-mediated activation of the canonical NF-κB pathway. In conclusion, aldosterone has an inflammatory effect in the corpus cavernosum penis, inducing NF-κB activation via an MRs-dependent pathway, which may be prevented by selective MRs antagonists. These data reveal the possible role of aldosterone in erectile dysfunction as well as its potential as a novel pharmacologic target for treatment.
Aldosterone/pharmacology* ; Animals ; Cytokines/biosynthesis* ; Gene Knockdown Techniques ; I-kappa B Kinase/antagonists & inhibitors* ; Interleukin-6/genetics* ; Male ; Mineralocorticoid Receptor Antagonists/pharmacology* ; NF-kappa B/genetics* ; Penis/metabolism* ; Protein Serine-Threonine Kinases/antagonists & inhibitors* ; RNA, Messenger/biosynthesis* ; Rats ; Rats, Inbred WKY ; Receptors, Mineralocorticoid/genetics* ; Signal Transduction/drug effects* ; Spironolactone/pharmacology* ; Transcriptional Activation ; Tumor Necrosis Factor-alpha/biosynthesis* ; NF-kappaB-Inducing Kinase

BACKGROUND:The number of elderly people (aged 60 years or over) is expected to double in the next 35 years as a result of decreasing mortality and declining fertility worldwide. The elderly population is at increased risk of being prescribed potentially inappropriate medications (PIM).
OBJECTIVES:To determine the prevalence of PIM prescribed among the geriatric patients admitted in a tertiary teaching hospital in Valenzuela City in 2014.
METHODS:This is a retrospective cross-sectional study on patients who are 65 years and older admitted under Internal Medicine between January 2014 to December 2014. Medical records were reviewed for PIM prescription according to the updated 2012 Beers Criteria.
RESULTS: PIMs were noted in 303 out of of 618 patients.The most common PIMs were insulin sliding scale, digoxin,orphenadrine, ipratropium, ketorolac, clonazepam, clonidine, hydroxyzine, amiodarone and spironolactone.
CONCLUSION:The prevalence of PIM prescription is 49% among geriatric patients admitted in a tertiary teaching hospital in Valenzuela City in 2014. It is recommended to determineprevalence of PIM use in other geriatric care settings, the predictors for PIM use, and the economic burden of PIM use.

Human ; Male ; Female ; Aged 80 And Over ; Aged ; Clonazepam ; Potentially Inappropriate Medication List ; Spironolactone ; Amiodarone ; Clonidine ; Ketorolac ; Orphenadrine ; Digoxin ; Ipratropium ; Insulin ; Hydroxyzine ; Fertility ; Prescriptions ; Patients

Gitelman's syndrome (GS), a hereditary disease characterized by hypokalemia, hypomagnesemia, and hypocalciuria, is a salt-losing renal tubulopathy. Herein, we describe a case of a 28-year-old woman diagnosed with atypical GS accompanying chondrocalcinosis. One year ago, she presented with vomiting, hypokalemic metabolic alkalosis, and hypocalciuria, and was tested by diuretic challenge test. As a result, she was diagnosed with atypical GS with normomagnesemia and treated with spironolactone and potassium supplementation. Meanwhile, acute arthritis of the right 1st metatarsophalangeal joint occurred. On the radiographies of the knees, chondrocalcinosis was observed. To the best of our knowledge, this is the first report in Korea of GS with chondrocalcinosis. Antialdosterone therapy or magnesium supplementation is effective in preventing the progression of chondrocalcinosis; thus, early diagnosis and treatment of GS are important.
Adult ; Alkalosis ; Arthritis ; Chondrocalcinosis* ; Early Diagnosis ; Female ; Genetic Diseases, Inborn ; Gitelman Syndrome* ; Humans ; Hypokalemia ; Knee ; Korea ; Magnesium ; Metatarsophalangeal Joint ; Potassium ; Spironolactone ; Vomiting

Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension. Risk factors for refractory hypertension include obesity, diabetes, chronic kidney disease, and especially, being of African origin. Patients with refractory are at high cardiovascular risk based on increased rates of known heart disease, prior stroke, and prior episodes of congestive heart failure. Mechanisms of refractory hypertension need exploration, but early studies suggest a possible role of heightened sympathetic tone as evidenced by increased office and ambulatory heart rates and higher urinary excretion of norepinephrine compared to patients with controlled resistant hypertension. Important negative findings argue against refractory hypertension being fluid dependent as is typical of resistant hypertension, including aldosterone levels, dietary sodium intake, and brain natriuretic peptide levels being similar or even less than patients with resistant hypertension and the failure to control blood pressure with use of intensive diuretic therapy, including both a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Further studies, especially longitudinal assessments, are needed to better characterize this extreme phenotype in terms of risk factors and outcomes and hopefully to identify effective treatment strategies.
Aldosterone ; Blood Pressure ; Heart Diseases ; Heart Failure ; Heart Rate ; Humans ; Hypertension* ; Natriuretic Peptide, Brain ; Norepinephrine ; Obesity ; Phenotype ; Receptors, Mineralocorticoid ; Renal Insufficiency, Chronic ; Risk Factors ; Sodium, Dietary ; Spironolactone ; Stroke ; Sympathetic Nervous System ; Treatment Failure*

BACKGROUND: Peritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin-angiotensin-aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT. METHODS: EMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, alpha-smooth muscle actin after stimulation with aldosterone (1-100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2',7'-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated. RESULTS: Aldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK. CONCLUSION: Aldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.
Actins ; Aldosterone* ; Antioxidants ; Blotting, Western ; Cadherins ; Cysteine ; Epithelial Cells ; Humans ; p38 Mitogen-Activated Protein Kinases ; Peritoneal Dialysis ; Peritoneal Fibrosis ; Peritoneum ; Phosphotransferases ; Protein Kinases ; Reactive Oxygen Species ; Receptors, Mineralocorticoid ; Renin-Angiotensin System ; Spironolactone

Stevens-Johnson syndrome (SJS) manifests with severe cutaneous reactions, most commonly triggered by medications, which are characterized by fever and mucocutaneous lesions leading to necrosis and sloughing of the epidermis. To our knowledge, pravastatin-induced SJS has not yet been reported. Here, we describe a case of SJS due to pravastatin, which was diagnosed by a patch test. A 70-year-old woman presented with maculopapular skin rashes, which developed 2 weeks after medication of bisoprolol, amlodipine, pravastatin, spironolactone, and indobufene for cardiac problems. Various bullous-erosive mucocutaneous lesions occupied less than 10% of the total body surface area. Painful oropharyngeal mucous membrane lesions were observed. The vermilion border of the lips became denuded and developed serosanguinous crusts. With the drug withdrawal and the use of systemic corticosteroids, her manifestations resolved. Drug patch tests with bisoprolol, amlodipine, pravastatin, spironolactone, and indobufene were performed, resulting in a positive reaction to pravastatin, but not to the other drugs. To the best of our knowledge, this is the first case of pravastatin-induced SJS.
Adrenal Cortex Hormones ; Aged ; Amlodipine ; Bisoprolol ; Body Surface Area ; Epidermis ; Exanthema ; Female ; Fever ; Humans ; Lip ; Mucous Membrane ; Necrosis ; Patch Tests ; Pravastatin ; Spironolactone ; Stevens-Johnson Syndrome*