cpap effect on albuminuria in patients with diabetic nephropathy and obstructive sleep apnea

Conditions: Diabetic Nephropathy; Sleep Apnea

Summary: objectives: main objective: to assess the effect of 12 months of cpap treatment added to conventional drug treatment on the albuminuria in patients with diabetic nephropathy and obstructive sleep apnea (osa). secondary objectives: to evaluate the effect of cpap treatment on the estimated glomerular filtration rate of patients with diabetic nephropathy and osa; determine the additional longterm cpap effect on glycemic control, insulin resistance, lipid profile, health-related quality of life and biomarkers of cardiac function, inflammation, oxidative stress, sympathetic tone and appetite-regulating hormones in patients with diabetic nephropathy and osa; and to identify the subgroup of patients with diabetic nephropathy and osa in which 12 months of treatment with cpap achieve a more pronounced reduction in albuminuria. methodology: randomized, multicenter, non-blinded, parallel groups, conventional treatment-controlled trial of 12 months of duration. subjects will randomize to conventional dietary and pharmacological treatment or conventional dietary and pharmacological treatment plus continuous positive airway pressure (cpap). study subjects: subjects 18 to 80 years with overweight or obesity and a clinical diagnosis of diabetic nephropathy, increased urinary albumin/creatinine ratio of 30 mg/g and an estimated glomerular filtration rate \>20 ml/min/1.73 m2, and treatment with stable doses of angiotensin-converting enzyme (ace) inhibitors, angiotensin ii receptor blockers (arbs) or anti-aldosterone drugs in the last four weeks. efficacy variables: urinary albumin/creatinine ratio and estimated glomerular filtration rate; glycosylated hemoglobin (hba1c); fasting glucose and insulin; homeostatic model assessment (homa) and quicki indices; total cholesterol, hdl-cholesterol, ldl-cholesterol, triglycerides; troponin i, probnp, homocysteine and high-sensitivity c-reactive protein; systemic biomarkers (inflammation \[il-6, il-8 and tumor necrosis factor-α\], oxidative stress \[8-isoprostane\], endothelial damage \[endothelin, vcam-1 and icam-1\], sympathetic activity \[neuropeptide y\] and appetite-regulating hormones \[leptin and adiponectin\]) and clinical questionnaires: short form (sf)-12, euroqol and ipaq.


Eligibility criteria:
inclusion criteria: * subjects aged 18 to 80 years old * overweight or obesity (bmi ≥25 kg/m2) * previous diagnosis of type 2 diabetes, fulfilling at least one of the following criteria: 1) current treatment with oral antidiabetic drugs and/or insulin; 2) a fasting glucose value above 126 mg/dl on at least 2 occasions; 3) blood glucose level at 2 hours after an oral glucose tolerance test is equal to or more than 200 mg/dl; or 4) a glycated hemoglobin (hba1c) level \> 6.5 % * clinical diagnosis of diabetic nephropathy, with a urinary albumin/creatinine ratio \>30 mg/g and an estimated glomerular filtration rate more than 20 ml/min per 1.73 m2. * treatment with stable doses of angiotensin-converting enzyme inhibitors, angiotensin ii receptor blockers or anti-aldosterone agents in the last four weeks. exclusion criteria: * non diabetic nephropathy (confirmed by biopsy). * dialysis for acute renal failure within the 6 previous months. * evidence in the clinic history of relevant bilateral stenosis of renal artery (\> 75%) * urinary albumin/creatinine ratio higher than 3000 mg/g, at the baseline visit. * systolic blood pressure ≥ 180 mmhg or diastolic blood pressure ≥ 110 mm hg at the baseline visit. * stroke, transient ischemic attack, acute coronary syndrome, or hospitalization for heart failure worsening, within the previous 30 days. * professional drivers, risk profession or respiratory failure. * severe daytime sleepiness (epworth sleepiness scale \>18) * concomitant treatment with high doses of acetylsalicylic acid (\> 500 mg/day) or continuous treatment with non-steroidal anti-inflammatory drugs * previous treatment with cpap * participation in another clinical trial within the 30 days prior to randomization.

Keywords: cpap sleep apnea diabetes nephropathy albuminuria