CENtral blood pressure Targeting: a pragmatic RAndomized triaL in advanced Chronic Kidney Disease (CENTRAL-CKD): A Clinical Research Protocol

Background: Emerging data favor central blood pressure (BP) over brachial cuff BP to predict cardiovascular and kidney events, as central BP more closely relates to the true aortic BP. Considering that patients with advanced chronic kidney disease (CKD) are at high cardiovascular risk and can have unreliable brachial cuff BP measurements (due to high arterial stiffness), this population could benefit the most from hypertension management using central BP measurements. Objective: To assess the feasibility and efficacy of targeting central BP as opposed to brachial BP in patients with CKD G4-5. Design: Pragmatic multicentre double-blinded randomized controlled pilot trial. Setting: Seven large academic advanced kidney care clinics across Canada. Patients: A total of 116 adults with CKD G4-5 (estimated glomerular filtration rate [eGFR] < 30 mL/min) and brachial cuff systolic BP between 120 and 160 mm Hg. The key exclusion criteria are 1) ≥ 5 BP drugs, 2) recent acute kidney injury, myocardial infarction, stroke, heart failure or injurious fall, 3) previous kidney replacement therapy. Methods: Double-blind randomization to a central or a brachial cuff systolic BP target (both < 130 mm Hg) as measured by a validated central BP device. The study duration is 12 months with follow-up visits every 2 to 4 months, based on local practice. All other aspects of CKD management are at the discretion of the attending nephrologist. Outcomes: Primary Feasibility : Feasibility of a large-scale trial based on predefined components. Primary Efficacy : Carotid-femoral pulse wave velocity at 12 months. Others : Efficacy (eGFR decline, albuminuria, BP drugs, and quality of life); Events (major adverse cardiovascular events, CKD progression, hospitalization, mortality); Safety (low BP events and acute kidney injury). Limitations: May be challenging to distinguish whether central BP is truly different from brachial BP to the point of significantly influencing treatment decisions. Therapeutic inertia may be a barrier to successfully completing a randomized trial in a population of CKD G4-5. These 2 aspects will be evaluated in the feasibility assessment of the trial. Conclusion: This is the first trial to evaluate the feasibility and efficacy of using central BP to manage hypertension in advanced CKD, paving the way to a future large-scale trial. Trial registration: clinicaltrials.gov (NCT05163158

Identification and Prioritization of Canadian Society of Nephrology Clinical Practice Guideline Topics With Multidisciplinary Stakeholders and People Living With Kidney Disease: A Clinical Research Protocol

Background: Despite efforts to provide evidence-based care for people living with kidney disease, health care provider goals and priorities are often misaligned with those of individuals with lived experience of disease. Coupled with competing interests of time, resources, and an abundance of suitable guideline topics, identifying and prioritizing areas of focus for the Canadian nephrology community with a patient-oriented perspective is necessary and important. Similar priority-setting exercises have been undertaken to establish research priorities for kidney disease and to standardize outcomes for kidney disease research and clinical care; however, research priorities are distinct from priorities for guideline development. Inclusion of people living with health conditions in the selection and prioritization of guideline topics is suggested by patient engagement frameworks, though the process to operationalizing this is variable. We propose that the Canadian Society of Nephrology Clinical Practice Guideline Committee (CSN CPGC) takes the opportunity at this juncture to incorporate evidence-based prioritization exercises with involvement of people living with kidney disease and their caregivers to inform future guideline activities. In this protocol, we describe our planned research methods to address this. Objective: To establish consensus-based guideline topic priorities for the CSN CPGC using a modified Delphi survey with involvement of multidisciplinary stakeholders, including people living with kidney disease and their caregivers. Study design: Protocol for a Modified Delphi Survey. Setting: Pilot-tested surveys will be distributed via email and conducted using the online platform SurveyMonkey, in both French and English. Participants: We will establish a group of multidisciplinary clinical and research stakeholders (both within and outside CSN membership) from Canada, in addition to people living with kidney disease and/or their caregivers. Methods: A comprehensive literature search will be conducted to generate an initial list of guideline topics, which will be organized into three main categories: (1) International nephrology-focused guidelines that may require Canadian commentary, (2) Non-nephrology specific guidelines from Canada that may require CSN commentary, and (3) Novel topics for guideline development. Participants will engage in a multi-round Modified Delphi Survey to prioritize a set of “important guideline topics.” Measures: Consensus will be reached for an item based on both median score on the Likert-type scale (≥ 7) and the percentage agreement (≥ 75%); the Delphi process will be complete when consensus is reached on each item. Guideline topics will then be given a priority score calculated from the total Likert ratings across participants, adjusted for the number of participants. Limitations: Potential limitations include participant response rates and compliance to survey completion. Conclusions: We propose to incorporate evidence-based prioritization exercises with the engagement of people living with kidney disease and their caregivers to establish consensus-based guideline topics and inform future guidelines activities of the CSN CPGC