Patients with obstructive sleep apnea (OSA) and diabetic kidney disease (DKD) who displayed good adherence to using continuous positive airway pressure (CPAP) appeared to reduce their albuminuria levels; however, CPAP prescription alone did not result in a statistically significant reduction in albuminuria. These were among study findings reported in American Journal of Respiratory and Critical Care Medicine.
Patients with OSA have increased risk of developing type 2 diabetes, impaired glucose intolerance, and insulin resistance. Moreover, the progression of diabetes could be aggravated by OSA leading to microvascular complications like DKD. Researchers evaluated the efficacy of CPAP on urinary albumin-to-creatinine ratio (UACR) in patients with OSA and DKD.
The year-long, multi-center, parallel, open-label, DIANA clinical trial (CPAP Effect on Albuminuria in Patients with Diabetic Nephropathy and Obstructive Sleep Apnea; ClinicalTrials.gov Identifier: NCT02816762), conducted at 6 teaching hospitals in Spain, included 185 patients with OSA and DKD randomized to CPAP plus usual care (n=93; 23% female) or usual care alone (n=92; 25% female). This trial was conducted from October 2016 through May 2020 at 6 teaching hospitals in Spain, coordinated by the Foundation for Biomedical Research of La Paz University Hospital.
Eligible patients (18-80 years of age) had type 2 diabetes and DKD. For at least 4 weeks they had received aldosterone receptor antagonists or stable doses of angiotensin-converting enzyme inhibitors. Sleep tests were self-administered in the homes of recruited participants who were eligible for randomization if their apnea-hypopnea index (AHI) was 10 or more events per hour. Random selection of participants was stratified by site and baseline UACR (<300mg/g or ≥300mg/g); both investigators and patients were aware of patient treatment assignments.
Patients were requested to maintain a regular 7 to 8 hour per night sleep schedule, stop smoking, and avoid sedatives and evening alcohol. Regular exercise, medication adherence, and a healthy diet were recommended. There were 74 patients in the CPAP group (mean age, 66 years) and 78 patients in the usual-care group (mean age, 68 years) who completed the 1-year follow-up. Researchers noted baseline characteristics and concomitant medications were similar between study groups.
CPAP was used a mean (SD) of 4.1 (2.9) hours per night, with 47 participants using CPAP it at least 4 hours per night. Mean CPAP pressure was 11 cmH2O and residual AHI following CPAP application was 2.6 events/hour.
Researchers found no statistically significant difference between the CPAP group and the usual-care group in UACR 1-year change from baseline. The between-group difference was -4.5% (95% CI, -11.1% to 2.2%; P =.19). UACR in non-sleepy patients with more severe OSA, more recent diagnosis of DKD, and worse renal function was more effected by CPAP. Insulin resistance, glycemic control, sleepiness, and health-related quality of life were improved with CPAP treatment.
Per-protocol analyses (n=125 participants with eligible criteria) showed CPAP associated significantly with UACR reduction (mean difference, -10.56%; 95% CI, -19.06 to -2.06; P =.015).
There were similar frequencies of serious adverse events (CPAP, 6 events; usual-care, 5 events) including 3 deaths (CPAP, 2; usual care, none). Nonserious adverse events included oronasal dryness (CPAP, 7 participants; usual care, none) with no other significant between-group differences in risks of nonserious adverse events.
Study limitations include the high loss to follow-up rate, analyses performed locally instead of centrally, sham CPAP not used, missing data during follow-up, and a preponderance of White European participants, thus limiting generalizability.
Researchers concluded that “In patients with OSA and DKD, the prescription of CPAP did not result in a statistically significant reduction in the albuminuria. However, good adherence to CPAP treatment in addition to usual care may result in long-term albuminuria reduction compared to usual care alone.” As their results indicated, “patients who showed adequate CPAP adherence experienced a significant reduction in UACR from baseline compared to patients who received usual care.”
Zamarrón E, Jaureguizar A, García-Sánchez A, et al.; DIANA investigators. CPAP effect on albuminuria progression in patients with obstructive sleep apnea and diabetic kidney disease. A randomized clinical trial. Am J Respir Crit Care Med. Published online November 7, 2022. doi:10.1164/rccm.202206-1091OC