Impact of Obstructive Sleep Apnea Treatment on Blood Pressure Control in Chronic Kidney Disease: A Randomized Trial

• Grant number: 23/07932-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2023
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Luciano Ferreira Drager
• Grantee: Larissa Teixeira Krul
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 19/23496-8 - Impact of sleep disorders on hypertension: a multifaceted approach, AP.TEM

Abstract

Chronic kidney disease (CKD) is an important public health problem worldwide, not only due to the increase in the population's life expectancy, but also due to the increased exposure to several comorbidities that can influence CKD. In parallel to traditional risk factors, there is a growing interest in addressing and treating emerging conditions. One of these potential candidates is Obstructive Sleep Apnea (OSA), a clinical condition characterized by partial or complete obstruction of the upper airways, causing an abrupt reduction in intrathoracic pressure, sleep fragmentation and intermittent hypoxemia. Recent evidence suggests that OSA is common, often underdiagnosed, and is associated with an increased frequency of CKD. However, the evidence on the potential impact of OSA on the management of CKD is not consistent. Specifically, whether OSA treatment can influence blood pressure (BP), pressure control aiming at more aggressive goals for these patients, as well as CKD progression, is still unclear. Therefore, we designed a randomized clinical trial to test the impact of OSA treatment on BP and on the evolution of the estimated glomerular filtration rate (eGFR) in patients with CKD IIIb and IV (eGFR 44-15 ml/min). A polygraph will be performed to assess the presence or absence of OSA (defined by an apnea-hypopnea index e15 events/hour). Patients with OSA will be randomized to use continuous positive upper airway pressure (CPAP) or to maintain optimized clinical treatment aimed at BP control. Antihypertensive medication adjustments will be allowed using a standard protocol for both groups by the same researcher who will not have access to CPAP follow-up. In addition to a clinical (including BP and ambulatory BP monitoring, ABPM) and laboratory assessment at baseline, we will follow up at 3 months, 6 months, 9 months and 12 months after randomization of the proposed outcomes.Analyzes of target organ damage such as the retina and echocardiography will be performed at baseline and after 1 year of randomization. Primary objective: to compare the effect of CPAP on the need to adjust antihypertensive medication in order to control systolic BP (<130mmHg) in chronic renal patients; secondary objectives: 1) Evaluate the reduction in systolic and diastolic BP by office measurements and ABPM; 2) Assessment of nocturnal BP drop using ABPM; 3) Evaluate the impact of OSA treatment with CPAP on eGFR during follow-up; 4) Evaluate the impact of OSA treatment with CPAP on the evolution of albuminuria; 5) assessment of other target organ damage such as retinopathy and cardiac remodeling; 6) Evaluate the impact of OSA treatment with CPAP on the possible delay for renal replacement therapy or end-stage renal disease (eGFR <15ml/min and dialysis indication by the Nephrology group); 7) Evaluate the impact of OSA treatment with CPAP on the quality of life of patients with CKD. With a significance level of 5% and study power of 90%, two-tailed hypothesis testing, 74 patients with OSA per group, i.e. 148 patients in total, will be required to assess the primary endpoint (we estimate that 25% and 50% of patients in the control and CPAP groups will not need to adjust their antihypertensive medication at follow-up, respectively).