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Current Opinion in Nephrology and... Jul 2024Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are... (Review)
Review
PURPOSE OF REVIEW
Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation.
RECENT FINDINGS
The clinical routine to prescribe thiazides for kidney stone prevention has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of recurrence. Yet, adverse events such as new onset diabetes mellitus and gout were more common in patients receiving hydrochlorothiazide compared to placebo. As demonstrated by a novel meta-analysis presented in this review encompassing all randomized placebo-controlled trials with thiazide monotherapy, current trial evidence does not indicate that thiazide monotherapy is significantly better than placebo in preventing kidney stone recurrence.
SUMMARY
Given the limited efficacy and possible adverse effects, we advocate for a restrictive use of thiazides for kidney stone recurrence prevention. Clearly, there remains a high unmet medical need for effective, targeted therapies to prevent recurrence of kidney stones.
Topics: Humans; Kidney Calculi; Secondary Prevention; Recurrence; Sodium Chloride Symporter Inhibitors; Thiazides; Treatment Outcome; Hydrochlorothiazide
PubMed: 38606682
DOI: 10.1097/MNH.0000000000000990 -
Journal of the Endocrine Society Mar 2024Hypophosphatemia (serum phosphate < 0.80 mmol/L) leads to musculoskeletal complaints. The most common drugs linked to hypophosphatemia are thiazide and loop diuretics,...
PURPOSE
Hypophosphatemia (serum phosphate < 0.80 mmol/L) leads to musculoskeletal complaints. The most common drugs linked to hypophosphatemia are thiazide and loop diuretics, but studies in the general population are lacking. Our aim was to study associations between diuretic use and serum phosphate in the Rotterdam Study (RS), a population-based cohort study, with replication in UK Biobank (UKBB).
METHODS
Associations between thiazide and loop diuretic use and serum phosphate and odds of hypophosphatemia were analyzed with cross-sectional multivariate linear and logistic regression in participants without chronic kidney disease in the RS and UKBB. Analyses were adjusted for age, sex, and body mass index (BMI) and pooled in 3 RS cohorts with further adjustment for cohort and serum potassium, which was not available in UKBB.
RESULTS
Thiazide diuretics were associated with lower serum phosphate in both sexes. This association lost significance in RS females after adjustment for BMI and in males after adjustment for serum potassium. Thiazide diuretics increased odds of hypophosphatemia in females in both cohorts and in males in UKBB only. Loop diuretics were associated with lower serum phosphate in females but not males. Adjustment for BMI attenuated these associations. Associations between loop diuretics and increased odds of hypophosphatemia in females lost significance after BMI adjustment.
CONCLUSION
Thiazides, but not loop diuretics, and increased BMI and decreased serum potassium should be considered as contributing factors in subjects with hypophosphatemia. Further studies are needed to replicate the findings and elucidate the potential role of hypokalemia as a mediator of this effect.
PubMed: 38572420
DOI: 10.1210/jendso/bvae057 -
Scientific Reports Sep 2023The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension...
The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension (HTN). A total of 5,195 patients, who were diagnosed with HTN between January 1, 2006 and December 31, 2015, and subsequently diagnosed with OAG, were selected for analysis. For each OAG patient, 5 non-glaucomatous, hypertensive controls were matched (n = 25,975) in hypertension diagnosis date, residential area, insurance type and economic status. Antihypertensive medications were stratified into 5 types: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), β-blockers and diuretics. Relative risks were calculated. After adjusting for age, sex, body mass index, lifestyle, comorbidities, blood pressure (BP), follow-up duration, and use of other types of antihypertensive drugs, ARB and CCB were found to slightly increase OAG risks (RR 1.1087 (95% CI 1.0293-1.1942); 1.0694 (1.0077-1.1349), respectively). Combinations of ARB with diuretics (1.0893 (1.0349-1.1466)) and CCB (1.0548 (1.0122-1.0991)) also increased OAG risks. The risks for OAG were found to increase by antihypertensive medication use, but the effects appeared to be small. Further studies are necessary to identify the associations of increased BP, medication and therapeutic effect with OAG.
Topics: Humans; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Glaucoma, Open-Angle; Calcium Channel Blockers; Hypertension; Diuretics
PubMed: 37758842
DOI: 10.1038/s41598-023-43420-3 -
Journal of Clinical Hypertension... Dec 2023The current screening and diagnostic recommendations for detecting Primary Hyperaldosteronism (PHA) focus on diagnosing the more severe and overt instances of... (Review)
Review
The current screening and diagnostic recommendations for detecting Primary Hyperaldosteronism (PHA) focus on diagnosing the more severe and overt instances of renin-independent aldosterone production. However, milder forms of autonomous aldosterone secretion have been demonstrated to exist below the diagnostic thresholds of current PHA guidelines, and associate with clinically relevant cardiovascular risk. PHAencompasses a spectrum of renin independent aldosterone production, progressing from a subclinical state in normotensives to a full-blown clinical syndrome representing the resistant hypertension population. The authors propose the Syndrome of Inappropriately Elevated Aldosterone Secretion (SIALDS) concept as a potential new paradigm for understanding and diagnosing PHA and expanded diagnostic approach to improve early detection even in well-controlled hypertension. The authors also delve into the impact of treatments, including mineralocorticoid receptor antagonists and emerging aldosterone synthase inhibitors. Furthermore, The authors outline future research directions, proposing clinical trials to investigate the long-term identification and treatment outcomes of SIALDS.
Topics: Humans; Hypertension; Aldosterone; Hyperaldosteronism; Renin; Blood Pressure; Mineralocorticoid Receptor Antagonists; Syndrome
PubMed: 37877173
DOI: 10.1111/jch.14740 -
JACC. Heart Failure Jan 2024The EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial established the efficacy of empagliflozin... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial established the efficacy of empagliflozin in reducing heart failure (HF) outcomes among patients with heart failure with reduced ejection fraction (HFrEF).
OBJECTIVES
The authors examined the outcomes of EMPEROR-Reduced as a function of background diuretic therapy.
METHODS
The EMPEROR-Reduced trial was a double-blind, randomized controlled trial of placebo vs empagliflozin 10 mg among 3,730 HFrEF patients. Herein, the population was stratified into 4 groups: no diuretic and diuretic dose equivalent to furosemide <40, 40, and >40 mg daily at baseline.
RESULTS
A total of 3,656 patients from the EMPEROR-Reduced trial were available for analysis. Of those patients, 482 (13.2%) were receiving no diuretic therapy, and 731 (20.0%), 1,411 (38.6%), and 1,032 (28.2%) were receiving <40 mg, 40 mg, and >40 mg, respectively. The efficacy of empagliflozin on the primary outcome (time to first event of hospitalization for HF or cardiovascular [CV] death) was consistent regardless of background diuretic therapy (>40 mg: HR: 0.88 [95% CI: 0.71-1.10]; 40 mg: HR: 0.65 [95% CI: 0.51-0.82]; <40 mg: HR: 0.65 [95% CI: 0.46-0.92]); no diuretic agents: HR: 0.78 [95% CI: 0.47-1.29]; P = 0.192). Baseline diuretic doses did not influence the effect of empagliflozin on body weight, systolic blood pressure, NT-proBNP, or hematocrit at 52 weeks. The safety profile of empagliflozin vs placebo was unaffected by baseline diuretic dose; however, independently of treatment allocation, total rates of adverse events were higher among patients with higher baseline doses of diuretic agents.
CONCLUSIONS
Empagliflozin exhibits a consistent effect on time to CV death or HF hospitalization and an unaltered safety profile regardless of baseline diuretic therapy. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).
Topics: Humans; Benzhydryl Compounds; Chronic Disease; Diuretics; Heart Failure; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 37715769
DOI: 10.1016/j.jchf.2023.06.036 -
Journal of the American College of... Apr 2024Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential.
OBJECTIVES
The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment.
METHODS
DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance.
RESULTS
Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70).
CONCLUSIONS
Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).
Topics: Aged; Humans; Middle Aged; Benzhydryl Compounds; Conservation of Water Resources; Diuresis; Diuretics, Osmotic; Glucosides; Heart Failure; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Function, Left; Water
PubMed: 38599715
DOI: 10.1016/j.jacc.2024.02.020 -
Archivos Peruanos de Cardiologia Y... 2023Nowadays, heart Failure (HF) is one of the main contributors of cardiovascular morbidity and mortality, this faces us with great challenges. The heart-kidney interaction... (Review)
Review
Nowadays, heart Failure (HF) is one of the main contributors of cardiovascular morbidity and mortality, this faces us with great challenges. The heart-kidney interaction receives particular attention due to the development of the so-called cardiorenal syndrome (CRS) and the diuretic resistance, latter is a predictor of adverse events in acute HF and is independent of the glomerular filtration rate. Development of diuretic resistance is secondary to multiple causes, so a comprehensive evaluation of all of them is required. In recent years, congestion has become relevant within the pathophysiological mechanism of CRS, as it mutually generates and perpetuates damage in these two organs. Given the importance of congestion, diuretics remain the cornerstone of treatment, although their use is largely empirical due to the limited evidence available. The evidence-based treatment paradigm is elusive in this scenario, so one question remains unanswered: Do the interventions to treat or to prevent the diuretic resistance modify the prognosis in acute HF?
PubMed: 38090203
DOI: 10.47487/apcyccv.v1i3.72 -
Cureus Sep 2023Globally, cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality. The risk of cardiovascular disease is markedly increased in... (Review)
Review
Globally, cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality. The risk of cardiovascular disease is markedly increased in individuals with type 2 diabetes mellitus (T2DM), making managing cardiovascular health a top priority. Initially developed for their glucose-lowering properties, sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a transformative class of pharmaceuticals with profound cardiovascular benefits that extend far beyond glycemic control. One of the most striking findings is the substantial reduction in major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and cardiovascular mortality, observed in clinical trials evaluating SGLT2 inhibitors. These extraordinary cardioprotective effects are demonstrated by landmark trials such as EMPA-REG OUTCOME, CANVAS, and DECLARE-TIMI 58, which are discussed in detail. In addition, SGLT2 inhibitors have demonstrated positive outcomes in heart failure (HF) with reduced ejection fraction, which has led to their incorporation into HF treatment guidelines. SGLT2 inhibitors offer renoprotection by delaying the progression of diabetic kidney disease, reducing albuminuria, preserving glomerular filtration rates, and their immediate cardiovascular benefits. We investigate the potential mechanisms underlying these renal benefits, focusing on the role of hemodynamic alterations and intraglomerular pressure reduction. In addition, SGLT2 inhibitors have a distinct diuretic effect that can contribute to volume reduction and symptom alleviation in patients with heart failure (HF). This diuretic action, distinct from conventional diuretics, warrants additional research to optimize their use in T2DM and HF patients. The risk of euglycemic diabetic ketoacidosis, genital mycobacterial infections, and bone fractures are also discussed. Understanding these issues is essential for making educated clinical decisions. In conclusion, SGLT2 inhibitors have transcended their initial function as anti-diabetic agents to become essential components of cardiovascular and renal protection strategies in T2DM patients. Their diverse benefits, which include cardioprotection, renoprotection, and the potential for HF management, highlight their potential to transform cardiovascular medicine. Optimizing the use of SGLT2 inhibitors in clinical practice bears the promise of improved cardiovascular outcomes for patients with T2DM and beyond as we navigate this changing landscape.
PubMed: 37908957
DOI: 10.7759/cureus.46243 -
Cutis Aug 2023A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness,... (Review)
Review
A range of treatment options are available for both mild to moderate and moderate to severe acne, and these options vary widely in their clinical uses, effectiveness, and costs. With the continued rise of dermatologic drug prices and increased cost-sharing due to high-deductible health plans, the importance of cost-effective treatment continues to grow. Failure to consider cost-effective, patient-centered care may lead to increased financial toxicity, reduced adherence, and ultimately worse outcomes and patient satisfaction. Combination topical products offer improved efficacy and convenience, which are associated with better adherence and outcomes. Generic fixed-dose adapalene-benzoyl peroxide (BPO) and fixed-dose clindamycin-BPO can be highly cost-effective options for patients with mild to moderate acne. Hormonal agents such as combined oral contraceptives (COCs) and spironolactone are inexpensive and likely reflect a highly cost-effective option that could reduce reliance on oral antibiotics in patients with moderate to severe acne. Doxycycline and isotretinoin also are cost-effective options for more severe acne. Frequent laboratory monitoring for spironolactone and isotretinoin continues to be prevalent despite little evidence to support its clinical utility, and it is associated with a major cost burden to the patient and health care system. The reduction of laboratory monitoring is an opportunity to provide higher-value care.
Topics: Humans; Dermatologic Agents; Benzoyl Peroxide; Isotretinoin; Adapalene; Cost-Benefit Analysis; Spironolactone; Drug Combinations; Acne Vulgaris; Treatment Outcome; Gels
PubMed: 37820334
DOI: 10.12788/cutis.0844 -
Clinical Pharmacokinetics Dec 2023Finerenone, a selective and nonsteroidal antagonist of the mineralocorticoid receptor, has received regulatory approval with the indication of cardiorenal protection in... (Review)
Review
Finerenone, a selective and nonsteroidal antagonist of the mineralocorticoid receptor, has received regulatory approval with the indication of cardiorenal protection in patients with chronic kidney disease associated with type 2 diabetes. It is rapidly and completely absorbed and undergoes first-pass metabolism in the gut wall and liver resulting in a bioavailability of 43.5%. Finerenone can be taken with or without food. The pharmacokinetics of finerenone are linear and its half-life is 2 to 3 h in the dose range of up to 20 mg. Cytochrome P450 (CYP) 3A4 (90%) and CYP2C8 (10%) are involved in the extensive biotransformation of finerenone to pharmacologically inactive metabolites, which are excreted via both renal (80%) and biliary (20%) routes. Moderate or severe renal impairment, or moderate hepatic impairment result in area-under-the-curve increases of finerenone (< 40%), which do not require a dose adjustment per se, as the starting dose is based on estimated glomerular filtration rate (eGFR) and titrated according to serum potassium levels and eGFR decline. No relevant effects of age, sex, body size or ethnicity on systemic finerenone exposure were identified. Modulators of CYP3A4 activity were found to affect finerenone exposure, consistent with its classification as a sensitive CYP3A4 substrate. Serum potassium should be monitored during drug initiation or dosage adjustment of either a moderate or weak CYP3A4 inhibitor or finerenone, and the dose of finerenone should be adjusted as appropriate. Its use with strong inhibitors is contraindicated and strong or moderate inducers of CYP3A4 should be avoided. Finerenone has no potential to affect relevant CYP enzymes and drug transporters.
Topics: Humans; Cytochrome P-450 CYP3A; Mineralocorticoid Receptor Antagonists; Diabetes Mellitus, Type 2; Potassium; Renal Insufficiency, Chronic
PubMed: 37875671
DOI: 10.1007/s40262-023-01312-9