Background: Emerging data favors aortic blood pressure (BP) over brachial cuff BP in predicting CV and renal complications, as this BP directly impacts the heart, brain and kidneys. In parallel, central BP measuring devices have been developed that are more accurate towards aortic BP and easy to use without training. In no other condition than advanced chronic kidney disease (CKD) is BP control as important, since undertreatment is associated with adverse CV events and progression towards end-stage kidney disease (ESKD), while overtreatment similarly leads to adverse CV events and injurious falls but also acute kidney injury which can precipitate ESKD. To this day, standard BP management relies on brachial cuff BP, which is an imprecise surrogate marker of aortic BP, more so in the advanced CKD population. Considering that these patients have a high risk of CV morbidity and mortality and is a group where brachial BP may be the least reliable, it can be beneficial to manage hypertension in this population using central BP measurements. With the development of affordable and easy to use central BP devices, routine use of central BP in hypertension would now become a reality. However, the superiority of central BP to traditional brachial cuff BP in regard to clinical outcomes will first need to be demonstrated.

Objectives: To demonstrate that targeting central BP in advanced CKD patients as opposed to brachial cuff BP is feasible and results in lower arterial stiffness after 12 months of follow-up.

Methods: The CENTRAL-CKD trial is an investigator-initiated prospective parallel-group 1:1 randomized double-blinded multicenter pragmatic pilot trial. Patients with CKD stages 4 and 5 (n=116) will be randomized to either a central systolic BP target < 130 mmHg (intervention) or brachial systolic BP target < 130 mmHg (standard care). Central and brachial BP will be concomitantly measured, with treating physicians, patients and investigators blinded towards allocation. As this trial is of a pragmatic design, all other aspects of BP and CKD management, including anti-hypertensive treatment-related decisions, diastolic BP targets, and clinical and laboratory follow-ups will be at the discretion of the attending Nephrologist. The primary outcomes include feasibility of large-scale trial using prespecified criteria and aortic stiffness (carotid-femoral pulse wave velocity) at 12 months. Other cardiovascular, renal, quality of life and safety outcomes will be evaluated.

Importance: CENTRAL-CKD is designed as a pilot trial aimed at providing the framework and justification to proceed to a large-scale trial with adequate power to detect the impact of the proposed intervention on clinically important outcomes.

Inclusion Criteria:

1. Over 18 years of age;
2. eGFR <30 mL/min/1.73m2 as determined by the CKD-EPI equation (within 30 days of screening);
3. Office brachial cuff systolic blood pressure between 120 and 160 mmHg (using automated office blood pressure).

Exclusion Criteria:

1. Already taking 5 or more anti-hypertensive medications (any class)
2. Unwillingness to change anti-hypertensive medication by the attending Nephrologist or patient
3. Recent acute kidney injury (>50% increase in serum creatinine in preceding 30 days)
4. Previous kidney replacement therapy (kidney transplant, hemodialysis or peritoneal dialysis)
5. Recent myocardial infarction, stroke, heart failure (in preceding 30 days)
6. Recent injurious fall requiring hospitalisation (in preceding 30 days)
7. Concomitant major illness / comorbidity that may result in death in the next 6 months
8. Participation in another study that is likely to affect BP levels
9. Inability to provide consent due to cognitive impairment.