Mechanisms of Antihypertensive Effect of Chlorthalidone in Advanced Chronic Kidney Disease: A Causal Mediation Analysis.

Key Points: Chlorthalidone reduces the amount of fluid and the BP, but fluid volume reduction is not the cause of lowering of BP. It is not volume loss but the response to volume loss such as the synthesis of substances that lower BP is important.

Background: Chlorthalidone (CTD) in a chronic kidney disease randomized trial demonstrated a robust reduction in systolic BP in stage 4 CKD.

VA-Based Peritoneal Dialysis Program Feasibility Considerations and Process Outline.

Background: Home dialysis utilization is lower among veterans than in the general US population. Several sociodemographic factors and comorbidities contribute to peritoneal dialysis (PD) underutilization. In 2019, the Veterans Health Administration (VHA) Kidney Disease Program Office convened a PD workgroup to address this concern.

Pharmacogenomics of Hypertension in CKD: The CKD-PGX Study.

Background: Patients with CKD often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may affect the metabolism or efficacy of antihypertensive agents. We report changes in hypertension control after providing a panel of 11 pharmacogenomic predictors of antihypertensive response.

Chlorthalidone for Hypertension in Advanced Chronic Kidney Disease.

Background: Little evidence has been available to support the use of thiazide diuretics to treat hypertension in patients with advanced chronic kidney disease.

Methods: We randomly assigned patients with stage 4 chronic kidney disease and poorly controlled hypertension, as confirmed by 24-hour ambulatory blood-pressure monitoring, in a 1:1 ratio to receive chlorthalidone at an initial dose of 12.5 mg per day, with increases every 4 weeks if needed to a maximum dose of 50 mg per day, or placebo; randomization was stratified according to previous use of loop diuretics.

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.

Implementation of a Renal Precision Medicine Program: Clinician Attitudes and Acceptance.

A precision health initiative was implemented across a multi-hospital health system, wherein a panel of genetic variants was tested and utilized in the clinical care of chronic kidney disease (CKD) patients. Pharmacogenomic predictors of antihypertensive response and genomic predictors of CKD were provided to clinicians caring for nephrology patients. To assess clinician knowledge, attitudes, and willingness to act on genetic testing results, a Likert-scale survey was sent to and self-administered by these nephrology providers (N = 76).

Clinical Pharmacology of Antihypertensive Therapy for the Treatment of Hypertension in CKD.

CKD is common and frequently complicated with hypertension both predialysis and in ESKD. As a major modifiable risk factor for cardiovascular disease in this high-risk population, treatment of hypertension in CKD is important. We review the mechanisms and indications for the major classes of antihypertensive drugs, including angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, -adrenergic blocking agents, dihydropyridine calcium channel blockers, thiazide diuretics, loop diuretics, mineralocorticoid receptor blockers, direct vasodilators, and centrally acting -agonists.

Setting the dry weight and its cardiovascular implications.

Volume overload is common and associated with adverse outcomes in the hemodialysis population including systemic hypertension, pulmonary hypertension, left ventricular hypertrophy, and mortality. Since the beginning of the era of maintenance dialysis, prescribing and maintaining a dry weight remains the standard of care for managing volume overload on hemodialysis. Reducing dry weight even by relatively small amounts has been shown to improve blood pressure and has been associated with reductions in left ventricular hypertrophy.

Masked Uncontrolled Hypertension in CKD.

Masked uncontrolled hypertension (MUCH) is diagnosed in patients treated for hypertension who are normotensive in the clinic but hypertensive outside. In this study of 333 veterans with CKD, we prospectively evaluated the prevalence of MUCH as determined by ambulatory BP monitoring using three definitions of hypertension (daytime hypertension ≥135/85 mmHg; either nighttime hypertension ≥120/70 mmHg or daytime hypertension; and 24-hour hypertension ≥130/80 mmHg) or by home BP monitoring (hypertension ≥135/85 mmHg). The prevalence of MUCH was 26.

Adverse effects of conventional thrice-weekly hemodialysis: is it time to avoid 3-day interdialytic intervals?

Background: Maintenance hemodialysis is typically scheduled thrice weekly due to simple logistic reasons; thus, the vast majority of hemodialysis patients receive renal replacement therapy for two shorter 2-day intervals and a longer 3-day interval. As compared to the 2-day interval, we review the ill effects of the longer 3-day interdialytic interval in this report.

Summary: Large-scale observational studies show that both cardiovascular-related hospital admissions and mortality occur more frequently on the day following the long interdialytic interval than on any other day of the week.

Thiazides in advanced chronic kidney disease: time for a randomized controlled trial.

Purpose Of Review: Chronic kidney disease is common, associated with increased cardiovascular risk, and frequently complicated by hypertension, requiring multiple agents for control. Thiazides are naturally attractive for use in this population; unfortunately, they are classically thought to be ineffective in advanced chronic kidney disease based on both theoretical considerations and the earliest studies of these agents. This report reviews the studies of thiazide use in chronic kidney disease since the 1970s, including five randomized controlled trials, all of which report at least some degree of efficacy.

Thiazide Diuretics in Chronic Kidney Disease.

Widely prevalent in the general population, chronic kidney disease (CKD) is frequently complicated with hypertension. Control of hypertension in this high-risk population is a major modifiable cardiovascular and renal risk factor but often requires multiple medications. Although thiazides are an attractive agent, guidelines have previously recommended against thiazide use in stage 4 CKD.

The complex relationship between CKD and ambulatory blood pressure patterns.

Hypertension and CKD frequently coexist, and both are risk factors for cardiovascular events and mortality. Among people with hypertension, the loss of the normal fall in night-time BP, called nondipping, can only be diagnosed by ambulatory BP monitoring (ABPM) and is a risk factor for cardiovascular events. The pathophysiology of nondipping is complex, and CKD is an independent risk factor for nondipping.

Hypertension Treatment for Patients with Advanced Chronic Kidney Disease.

Chronic kidney disease is common and frequently complicated with hypertension. As a major modifiable risk factor for cardiovascular disease in this high risk population, treatment of hypertension in chronic kidney disease is of paramount importance. We review the epidemiology and pathogenesis of hypertension in chronic kidney disease and then update the latest study results for treatment including salt restriction, invasive endovascular procedures, and pharmacologic therapy.

Chlorthalidone for poorly controlled hypertension in chronic kidney disease: an interventional pilot study.

To test the hypothesis that thiazide-type diuretics effectively lower blood pressure (BP) in moderate to advanced chronic kidney disease (CKD; estimated GFR 20-45 ml/min/ 1.73 m(2)), after confirming poorly controlled hypertension with 24-hour ambulatory BP monitoring, chlorthalidone was added to existing medications in a dose of 25 mg/day, and the dose doubled every 4 weeks if the BP remained elevated. The average age of the 14 subjects was 67.

Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial.

Background: The purpose of this study was to determine among maintenance hemodialysis patients with echocardiographic left ventricular hypertrophy and hypertension whether in comparison with a β-blocker-based antihypertensive therapy, an angiotensin converting enzyme-inhibitor-based antihypertensive therapy causes a greater regression of left ventricular hypertrophy.

Methods: Subjects were randomly assigned to either open-label lisinopril (n = 100) or atenolol (n = 100) each administered three times per week after dialysis. Monthly monitored home blood pressure (BP) was controlled to <140/90 mmHg with medications, dry weight adjustment and sodium restriction.

Chronic renal disease progression: treatment strategies and potassium intake.

Disordered potassium homeostasis is a common complication of chronic kidney disease and traditional management focuses on restricting potassium intake to avoid hyperkalemia. Permissive potassium intake carries the risk of hyperkalemia and hyperphosphatemia, and possibly may contribute to the development of uremic neuropathy. Excessive potassium restriction and removal by dialysis carries the risk of worsened chronic hypertension, intradialytic hypotension, renal fibrosis and cyst formation, and ventricular arrhythmias.

Shorter delivered dialysis times associate with a higher and more difficult to treat blood pressure.

Background: Shorter delivered dialysis times are associated with increased all-cause mortality. Whether shorter delivered dialysis times also associate with an increase in blood pressure (BP) and reduce the ability of probing dry weight to lower BP is unclear.

Methods: Among patients participating in the Dry-Weight Reduction in Hypertensive Hemodialysis Patients (DRIP) trial, interdialytic ambulatory BP was recorded at baseline, 4 weeks and 8 weeks.

Determinants and short-term reproducibility of relative plasma volume slopes during hemodialysis.

Background And Objectives: Hypervolemia is a major cause of morbidity, in part because of the lack of well characterized diagnostic tests. The hypothesis was that relative plasma volume (RPV) slopes are influenced by ultrafiltration rate, directly associate with improvement in arterial oxygen saturation, and are reproducible.

Design, Setting, Participants, & Measurements: RPV slopes were measured on three consecutive hemodialysis sessions.