Abstract
INTRODUCTION: Lower estimated glomerular filtration rate (eGFR) and more severe albuminuria categories are associated with increased risk for adverse outcomes such as mortality, cardiovascular and kidney outcomes. The aim of the analysis was to evaluate whether nocturnal hypoxemic burden (NHB) is associated with worsening prognosis of CKD in a population with T2D. METHODS: Overnight oximetry data from patients enrolled in the DIACORE (DIAbetes COhoRtE) sleep-disordered breathing sub-study, a prospective cohort study of patients with T2D, was analyzed and NHB as cumulative time spent below 90% oxygen saturation (T90) was quantified. Very-high-risk CKD was defined according to KDIGO risk classification: eGFR < 30 ml/min/1.73 m(2) regardless of urinary albumin-to-creatinine ratio (uACR); eGFR < 45 ml/min/1.73 m(2) and uACR > 30 mg albumin/g creatinine; or eGFR < 60 ml/min/1.73 m(2) and uACR > 300 mg/g. Logistic regression analyses adjusting for known risk factors for CKD prognosis were performed to assess the association between NHB and incident very-high-risk CKD. RESULTS: The analysis population comprised 857 participants (41% female, mean age 65 years, median diabetes duration 9.0 years, median eGFR 82 ml/min/1.73 m(2)). During follow-up, 72 (8.4%) patients developed very-high-risk CKD, and patients with high T90 significantly more often developed very-high-risk CKD than patients with lower T90 (quartile 4 vs. quartiles 1-3: 15.0 vs. 6.2%, p < 0.001). NHB was significantly associated with an increased incidence of very-high-risk CKD. Patients in the highest quartile of T90 had a 3.0-fold higher risk compared to patients in the lowest quartile, independently of other risk factors for CKD prognosis such as age, sex, waist-hip ratio, hypertension, antihypertensive and lipid-lowering medication, HbA1c, diabetes duration, and eGFR and hemoglobin levels at baseline (OR 2.96, 95% CI (1.24; 7.07), p = 0.014; p for trend 0.013). CONCLUSION: We identified NHB as a novel risk factor for worsening CKD prognosis in patients with T2D. Further research is needed to ascertain whether T90 reduction constitutes a clinically meaningful prevention target. TRIAL REGISTRATION: German Clinical Trials Register DRKS00010498.