- Browse by Subject
Browsing by Subject "Spironolactone"
Now showing 1 - 8 of 8
Results Per Page
Sort Options
Item Hypertension in chronic kidney disease—treatment standard 2023(Oxford University Press, 2023) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of MedicineHypertension is very common and remains often poorly controlled in patients with chronic kidney disease (CKD). Accurate blood pressure (BP) measurement is the essential first step in the diagnosis and management of hypertension. Dietary sodium restriction is often overlooked, but can improve BP control, especially among patients treated with an agent to block the renin–angiotensin system. In the presence of very high albuminuria, international guidelines consistently and strongly recommend the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker as the antihypertensive agent of first choice. Long-acting dihydropyridine calcium channel blockers and diuretics are reasonable second- and third-line therapeutic options. For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen. However, the associated risk of hyperkalemia restricts the broad utilization of spironolactone in patients with moderate-to-advanced CKD. Evidence from the CLICK (Chlorthalidone in Chronic Kidney Disease) trial indicates that the thiazide-like diuretic chlorthalidone is effective and serves as an alternative therapeutic opportunity for patients with stage 4 CKD and uncontrolled hypertension, including those with treatment-resistant hypertension. Chlorthalidone can also mitigate the risk of hyperkalemia to enable the concomitant use of spironolactone, but this combination requires careful monitoring of BP and kidney function for the prevention of adverse events. Emerging agents, such as the non-steroidal mineralocorticoid receptor antagonist ocedurenone, dual endothelin receptor antagonist aprocitentan and the aldosterone synthase inhibitor baxdrostat offer novel targets and strategies to control BP better. Larger and longer term clinical trials are needed to demonstrate the safety and efficacy of these novel therapies in the future. In this article, we review the current standards of treatment and discuss novel developments in pathophysiology, diagnosis, outcome prediction and management of hypertension in patients with CKD.Item Management of hypertension in advanced kidney disease(Wolters Kluwer, 2022) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of MedicinePurpose of review: The aim of this study was to present recent developments in pharmacotherapy of hypertension in patients with advanced chronic kidney disease (CKD). Recent findings: In the AMBER trial, compared with placebo, the potassium-binder patiromer mitigated the risk of hyperkalaemia and enabled more patients with uncontrolled resistant hypertension and stage 3b/4 CKD to tolerate and continue spironolactone treatment; add-on therapy with spironolactone provoked a clinically meaningful reduction of 11-12 mmHg in unattended automated office SBP over 12 weeks of follow-up. In the BLOCK-CKD trial, the investigational nonsteroidal mineralocorticoid-receptor-antagonist (MRA) KBP-5074 lowered office SBP by 7-10 mmHg relative to placebo at 84 days with a minimal risk of hyperkalaemia in patients with advanced CKD and uncontrolled hypertension. The CLICK trial showed that the thiazide-like diuretic chlorthalidone provoked a placebo-subtracted reduction of 10.5 mmHg in 24-h ambulatory SBP at 12 weeks in patients with stage 4 CKD and poorly controlled hypertension. Summary: Enablement of more persistent spironolactone use with newer potassium-binding agents, the clinical development of novel nonsteroidal MRAs with a more favourable benefit-risk profile and the recently proven blood pressure lowering action of chlorthalidone are three therapeutic opportunities for more effective management of hypertension in high-risk patients with advanced CKD.Item Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease(Elsevier, 2021-06-10) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of MedicineThe overactivation of the mineralocorticoid receptor (MR) in animal models of chronic kidney disease (CKD) increases sodium retention and hypertension and provokes inflammation and fibrosis in the kidneys, blood vessels, and the heart; these processes play an important role in the progression of cardiorenal disease. Accordingly, blockade of the MR is an attractive therapeutic intervention to retard the progression of CKD and improve cardiovascular morbidity and mortality. Finerenone is a novel, nonsteroidal MR antagonist (MRA) with a unique mode of action that is distinct from currently available steroidal MRAs. In animal models of CKD, finerenone has a more favorable benefit/risk ratio as compared with the steroidal MRAs such as spironolactone and eplerenone. In patients with type 2 diabetes and heart and/or kidney disease, phase II trials have revealed that compared with spironolactone, eplerenone, or placebo, finerenone displays benefits that exceed the risks of MR antagonism. In patients with CKD and type 2 diabetes, a large phase III trial has shown that, compared with placebo, finerenone improved kidney failure and cardiovascular outcomes. In the first part of this article, we explore the safety and efficacy of spironolactone and eplerenone in early- and late-stage CKD. In the second part, we describe the mechanism of action of finerenone and discuss the promising role of this nonsteroidal MRA as a novel therapeutic opportunity to improve clinical outcomes in patients with CKD.Item Patiromer and Spironolactone in Resistant Hypertension and Advanced CKD: Analysis of the Randomized AMBER Trial(American Society of Nephrology, 2021-01-15) Agarwal, Rajiv; Rossignol, Patrick; Budden, Jeffrey; Mayo, Martha R.; Arthur, Susan; Williams, Bryan; White, William B.; Medicine, School of MedicineBackground: Mineralocorticoid receptor antagonists reduce mortality in patients with heart failure with reduced ejection fraction and have become a standard of care in those with resistant hypertension (rHTN). Yet, their use is limited among patients with CKD, primarily due to hyperkalemia. Methods: AMBER was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that reported that the use of the potassium-binding drug patiromer allowed a more persistent use of spironolactone in patients with CKD and rHTN. In this report, we compare the safety and efficacy of patiromer in advanced CKD as a prespecified analysis. Results: Of the 295 patients randomized, 66 fell into the eGFR 25 to <30 subgroup. In this subgroup, persistent use of spironolactone was seen in 19 of 34 (56%) in the placebo group and 27 of 32 (84%) in the patiromer group (absolute difference 29%; P<0.02). In the eGFR 30-45 subgroup, persistent use of spironolactone was seen in 79 of 114 (69%) in the placebo group and 99 of 115 (86%) in the patiromer group (absolute difference 17%; P=0.003). There was no significant interaction between eGFR subgroups (P=0.46). Systolic BP reduction with spironolactone in the eGFR 25 to <30 subgroup was 6-7 mm Hg; in the eGFR 30-45 subgroup, it was 12-13 mm Hg. There was no significant interaction between eGFR subgroups on BP reduction (P=0.79). Similar proportions of patients reported adverse events (59% in the eGFR 25 to <30 subgroup; 53% in the eGFR 30-45 subgroup). Conclusions: Patiromer facilitates the use of spironolactone among patients with rHTN, and its efficacy and safety are comparable in those with eGFR 25 to <30 and 30-45 ml/min per 1.73 m2.Item Patiromer to Enable Spironolactone in Patients with Resistant Hypertension and CKD (AMBER): Results in the Prespecified Subgroup with Diabetes(Wolters Kluwer, 2021) Agarwal, Rajiv; Rossignol, Patrick; Mayo, Martha R.; Conrad, Ansgar; Arthur, Susan; Williams, Bryan; White, William B.; Medicine, School of MedicineItem Patiromer to Enable Spironolactone Use in the Treatment of Patients with Resistant Hypertension and Chronic Kidney Disease: Rationale and Design of the AMBER Study(Karger Publishers, 2018) Agarwal, Rajiv; Rossignol, Patrick; Garza, Dahlia; Mayo, Martha R.; Warren, Suzette; Arthur, Susan; Romero, Alain; White, William B.; Williams, Bryan; Medicine, School of MedicineBACKGROUND: While chronic kidney disease (CKD) is common in resistant hypertension (RHTN), prior studies -evaluating mineralocorticoid receptor antagonists excluded patients with reduced kidney function due to risk of hyperkalemia. AMBER (ClinicalTrials.gov identifier NCT03071263) will evaluate if the potassium-binding polymer patiromer used concomitantly with spironolactone in patients with RHTN and CKD prevents hyperkalemia and allows more persistent spironolactone use for hypertension management. METHODS: Randomized, double-blind, placebo-controlled parallel group 12-week study of patiromer and spironolactone versus placebo and spironolactone in patients with uncontrolled RHTN and CKD. RHTN is defined as unattended systolic automated office blood pressure (AOBP) of -135-160 mm Hg during screening despite taking ≥3 antihypertensives, including a diuretic, and an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker -(unless not tolerated or contraindicated). The CKD inclusion criterion is an estimated glomerular filtration rate (eGFR) of 25 to ≤45 mL/min/1.73 m2. Screening serum potassium must be 4.3-5.1 mEq/L. The primary efficacy endpoint is the between-group difference (spironolactone plus patiromer versus spironolactone plus placebo) in the proportion of patients remaining on spironolactone at Week 12. RESULTS: Baseline characteristics have been analyzed as of March 2018 for 146 (of a targeted 290) patients. Mean (SD) baseline age is 69.3 (10.9) years; 52.1% are male, 99.3% White, and 47.3% have diabetes. Mean (SD) baseline serum potassium is 4.68 (0.25) mEq/L, systolic AOBP is 144.3 (6.8) mm Hg, eGFR is 35.7 (7.7) mL/min/1.73 m2. CONCLUSION: AMBER will define the ability of patiromer to facilitate the use of spironolactone, an effective antihypertensive therapy for patients with RHTN and CKD.Item The Utility of Monitoring Potassium in Transgender, Gender Diverse, and Nonbinary Individuals on Spironolactone(Oxford University Press, 2022-09-12) Hayes, Hailey; Russell, Rachel; Haugen, Amber; Nagavally, Sneha; Sarvaideo, Jenna; Pediatrics, School of MedicineContext: Current Endocrine Society guidelines recommend that transgender women taking spironolactone have their potassium levels checked every 3 months for the first year after initiating therapy and annually thereafter to monitor for hyperkalemia. Objective: The goal of this study was to assess the need for such frequent potassium monitoring and to investigate whether age plays a role in potassium abnormalities in transgender, gender diverse, and nonbinary (TGDNB) individuals taking spironolactone. Methods: Using EPIC-Clarity, a retrospective study of healthy, adult individuals with gender-identity disorder listed in their problem list and taking spironolactone was performed. We analyzed the incidence of hyperkalemia in this population. Data from June 2006 through November 2021 were obtained. Exclusion criteria included hypertension, renal failure, diabetes mellitus, heart failure, and medications that affect the renin-angiotensin-aldosterone system. Results: 318 healthy TGDNB individuals met our inclusion criteria. We identified 8/318 (2.5%) individuals with hyperkalemia on spironolactone. There was a significant difference in incidence of hyperkalemia events in those >45 years old and those ≤45 years old (8.9% vs 1.5%, P = .016). Conclusion: Our data suggest the incidence of hyperkalemia in our TGDNB population is low, particularly in those ≤45 years old; however, this risk increases with age. These findings suggest practice guidelines may need to be adjusted to minimize unnecessary testing in the population ≤45 years old who are not plagued by comorbidities that affect potassium handling.Item The Use of Aldosterone Receptor Blockers in the Treatment of Hypertension(Wiley, 2004-11) Weinberger, Myron H.; Medicine, School of MedicineThe emerging role of aldosterone in hypertension and cardiovascular diseases has prompted a renewal of interest in therapeutic approaches designed to interfere with the action of this mineralocorticoid hormone. While spironolactone has long been used for this purpose, side effects, largely attributable to the interaction of this agent with non-mineralocorticoid steroid receptors, has reduced the enthusiasm for its use. Eplerenone, a specific aldosterone receptor blocker with a lower incidence of the sex hormone-related side effects than spironolactone, has been used in several recent clinical trials in hypertension and congestive heart failure. This review will highlight the major findings from these studies.