Should we CLICK on chlorthalidone for treatment-resistant hypertension in chronic kidney disease?

Treatment-resistant hypertension is common among patients with advanced chronic kidney disease (CKD). In people with preserved kidney function, spironolactone is an evidence-based treatment. However, the risk for hyperkalemia limits its use in people with more advanced CKD.

Effects of Bardoxolone Methyl in Alport Syndrome.

Background And Objectives: Alport syndrome is an inherited disease characterized by progressive loss of kidney function. We aimed to evaluate the safety and efficacy of bardoxolone methyl in patients with Alport syndrome.

Design, Setting, Participants, & Measurements: We randomly assigned patients with Alport syndrome, ages 12-70 years and eGFR 30-90 ml/min per 1.

The Nonsteroidal Mineralocorticoid-Receptor-Antagonist Finerenone in Cardiorenal Medicine: A State-of-the-Art Review of the Literature.

Steroidal mineralocorticoid-receptor-antagonists (MRAs), such as spironolactone and eplerenone, are guideline-directed therapies in patients with heart failure with reduced ejection fraction or resistant hypertension. However, the associated risk of hyperkalemia and hormonal side effects limit their broad use and downstream cardiorenal protection in high-risk patients with type 2 diabetes mellitus (T2DM) and moderate-to-advanced chronic kidney disease (CKD). The critical unmet need to improve long-term cardiorenal outcomes in such patients with CKD has sparked considerable efforts to the discovery and development of a new class of compounds.

Effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on cardiovascular outcomes in dialysis patients: a systematic review and meta-analysis.

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) are recommended by guidelines as first-line antihypertensive therapies in the general population or in patients with earlier stages of kidney disease. However, the cardioprotective benefit of these agents among patients on dialysis remains uncertain.

Methods: We searched the MEDLINE, PubMed and Cochrane databases from inception through February 2022 to identify randomized controlled trials (RCTs) comparing the efficacy of ACEIs/ARBs relative to placebo or no add-on treatment in patients receiving dialysis.

Management of hypertension in advanced kidney disease.

Purpose 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.

Mineralocorticoid Receptor Antagonism in Chronic Kidney Disease.

The 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.

Home blood pressure monitoring: methodology, clinical relevance and practical application: a 2021 position paper by the Working Group on Blood Pressure Monitoring and Cardiovascular Variability of the European Society of Hypertension.

The present paper provides an update of previous recommendations on Home Blood Pressure Monitoring from the European Society of Hypertension (ESH) Working Group on Blood Pressure Monitoring and Cardiovascular Variability sequentially published in years 2000, 2008 and 2010. This update has taken into account new evidence in this field, including a recent statement by the American Heart association, as well as technological developments, which have occurred over the past 20 years. The present document has been developed by the same ESH Working Group with inputs from an international team of experts, and has been endorsed by the ESH.

Sex difference in ambulatory blood pressure control associates with risk of ESKD and death in CKD patients receiving stable nephrology care.

Background: It is unknown whether faster progression of chronic kidney disease (CKD) in men than in women relates to differences in ambulatory blood pressure (ABP) levels.

Methods: We prospectively evaluated 906 hypertensive CKD patients (553 men) regularly followed in renal clinics to compare men versus women in terms of ABP control [daytime <135/85 and nighttime blood pressure (BP) <120/70 mmHg] and risk of all-cause mortality and end-stage kidney disease (ESKD).

Results: Age, estimated glomerular filtration rate and use of renin-angiotensin system inhibitors were similar in men and women, while proteinuria was lower in women [0.

NIH Funding, Research Productivity, and Scientific Impact: a 20-Year Study.

Background: The Research Project Grant (R01) is the oldest grant mechanism used by the National Institutes of Health (NIH). Receiving an R01 award is often taken as a sign of scientific success. We presented normative data on multiple productivity and impact metrics for a more objective assessment of funded grants' scientific success.

Hypertension in Chronic Kidney Disease (CKD): Diagnosis, Classification, and Therapeutic Targets.

Blood pressure (BP) in the office is often recorded without standardization of the technique of measurement. When office BP measurement is performed with a research-grade methodology, it can inform better therapeutic decisions. The reference-standard method of ambulatory BP monitoring (ABPM) together with the assessment of BP in the office enables the identification of white-coat and masked hypertension, facilitating the stratification of cardiorenal risk.

Resistant Hypertension in Chronic Kidney Disease (CKD): Prevalence, Treatment Particularities, and Research Agenda.

Purpose Of Review: To explore the prevalence, treatment particularities, and research agenda in the management of resistant hypertension among patients with chronic kidney disease (CKD).

Recent Findings: The prevalence of resistant hypertension is reported to be 2-3 times higher in patients with CKD than in the general hypertensive population. Based in part on the results of the PATHWAY-2 trial showing add-on spironolactone to be superior to placebo or active treatment with an α- or β-blocker in reducing BP, international guidelines recommend the use of spironolactone as fourth-line agent in pharmacotherapy of resistant hypertension.

Design and Baseline Characteristics of the Chlorthalidone in Chronic Kidney Disease (CLICK) Trial.

Background: Hypertension often accompanies chronic kidney disease (CKD), and diuretics are widely prescribed to reduce blood pressure (BP). Chlorthalidone (CTD) is a thiazide-like diuretic and an effective antihypertensive drug, yet little data exist to support its use in treating hypertension in individuals with advanced CKD.

Methods: Chlorthalidone in Chronic Kidney Disease (CLICK) is a phase II, single-institution, multicenter, double-blind randomized control trial to test the hypothesis that CTD improves BP, through reduction of extracellular fluid volume, and results in target organ protection in patients with stage 4 CKD and poorly controlled hypertension.

Antihypertensive Therapy in Patients Receiving Maintenance Hemodialysis: A Narrative Review of the Available Clinical-Trial Evidence.

Background: Blood pressure (BP)-lowering with the use of antihypertensive drugs appears to protect the cardiovascular (CV) system in hemodialysis patients. However, the optimal treatment algorithm of hypertension remains elusive; extrapolation of clinical-trial evidence from the general population may not be optimal.

Methods: For this narrative review, we searched the Medline/PubMed database (inception to August 01, 2019) to identify randomized clinical trials evaluating the efficacy of antihypertensive drugs on CV outcomes and mortality in patients on hemodialysis.

Systolic and diastolic hypertension among patients on hemodialysis: Musings on volume overload, arterial stiffness, and erythropoietin.

Hypertension among patients on hemodialysis is predominantly systolic (either isolated or combined with diastolic hypertension), whereas the scenario of isolated diastolic hypertension is rare and more common in younger patients. Uncontrolled hypertension that persists despite aggressive antihypertensive drug therapy is a reflection of the volume overload that is a prominent mediator of systolic and diastolic BP elevation. Clinical-trial evidence supports the notion that dry-weight probing is an effective strategy to improve BP control, even when overt clinical signs and symptoms of volume overload are not present.

A longitudinal study of the effects of age, sex and race on body composition in chronic kidney disease.

Background: Chronic kidney disease (CKD) is characterized by accelerated aging, but the age-related changes in body composition and its modification by sex and race are unclear.

Methods: We assembled a cohort of 516 patients with CKD and 45 healthy controls and serially measured body composition using air-displacement plethysmography for up to 6 years. Mixed models were used to evaluate simultaneously the baseline and longitudinal changes in body composition as influenced by age, sex and race.