Effects of Renin-Angiotensin System Inhibitors in Peritoneal Dialysis Patients

Effects of Renin-Angiotensin System Inhibitors on Mortality and Cardiovascular Outcomes in Peritoneal Dialysis Patients: A Retrospective Cohort Study in Thailand

Among antihypertensive medications, RAS inhibitor classes, namely angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) have the most prospective data on mortality and cardiovascular outcomes in specific high-risk populations with mild to moderate chronic kidney disease (CKD). Whereas, long-term data on the risks and benefits of ACEI/ARB usage in end-stage kidney disease (ESKD) patients undergoing peritoneal dialysis (PD) are limited. Recently, increasing clinical studies suggested that ACEI/ARB had a beneficial effect on intermediate outcomes, including short-term blood pressure variability, left ventricular hypertrophy, and may have an important role in the peritoneum and the kidney protection. Subsequently, treatment with ACEI/ARB has been recommended by the International Society for Peritoneal Dialysis for PD patients with significant residual kidney function (RKF).

Although existing reviews demonstrated that ACEI/ARB significantly has benefit in preserving RKF in PD patients, evidence regarding the relative efficacy on mortality, cardiovascular outcomes, and adverse events is lacking. Given that there exist few controlled trials of the effectiveness of ACEI/ARB in PD patients, we intend to perform a retrospective cohort study to assess the association between the use of ACEI/ARB and the risk of long-term mortality, cardiovascular outcomes, and adverse events in terms of hyperkalemia.

A retrospective cohort of Thai PD patients will be constructed by using the local joint registry data of adult PD patients from five centers in Thailand between 2006 to 2017 and followed to December 2018. We will link the following health datasets: (i) the electronic health records, contains outpatient and inpatient data; (ii) the Support System Pharmacy Dispensing extract, an administrative database which covers pharmacy dispensing; (iii) the PD Patient Care Database, which provides patient-level detail on sociodemographic and clinical characteristics as well as long-term PD care data; and (iv) the Laboratory Support System extract, which includes claims and routine laboratory results.

The exposure of interest in this cohort will be the use of ACEI/ARB within a 90-day after the date of PD initiation. Outcomes of interest will include all-cause mortality, cardiovascular mortality, a composite endpoint of cardiovascular events, and adverse events in terms of hyperkalemia.

Inclusion Criteria:

• Adult patients aged 18 years or over at the date of PD initiation
• Patients with ESKD who were undergoing PD either continuous ambulatory peritoneal dialysis or automated peritoneal dialysis between January 1, 2006, to December 31, 2017
• Received PD treatment more than 90 days in an outpatient nephrology clinic visit after the date of PD initiation
• Received of any outpatient prescriptions within 90 days after the date of PD initiation

Exclusion Criteria:

• Previously been treated by maintenance hemodialysis (for more than 90 days) or initiated PD for acute kidney injury or after a failed kidney transplantation
• Died within 90 days after the date of PD initiation
• Received a combination of ACEIs and ARBs therapy
• Received ACEIs/ARBs within 180 days before PD initiation
• Had no information regarding ACEI/ARB dosage regimen during the follow-up period
• Inadequate follow-up clinical information on blood pressure monitoring