Effect of CPAP in the Worsening of Renal Function in Early Stages of Chronic Kidney Disease (CKD)

Study Overview
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Brief Summary
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Objectives: Evaluate the effect of CPAP to reduce the progression of chronic kidney disease or CKD (the decline of glomerular filtration rate is ≥ 30%) in patients with early-stage renal disease and sleep apnea syndrome (OSAS). Other objectives are; determine the prevalence of OSAS in patients with early-stage renal disease and evaluate the changes in inflamatories markers and endothelial damage, the state of KDIGO, cardiovascular events, mortality and cost-effectiveness analysis in CPAP group versus non-CPAP group patients. Methods: A prospective, multicentric, randomized and controlled study will be carried out for 3 years. Early-stage renal disease (G1-3 KDIGO) and OSAS patients will be included. The investigators will make a respiratory polygraphy to determinate OSAS (AHI ≥15/h) and after that, the investigators randomized patients in 2 groups; CPAP group and control group (non-CPAP treatment). Patients with AHI <15/h (non-OSAS) will be the reference group and the half of these patients, randomly chosen, will be followed up at the end of the follow up. Statistic analysis: the investigators will analyze the differences in glomerular filtration rate before and after the treatment, comparing the percentage of patients with CKD progression for both groups. The investigators will use the chi square test with raw data and adjusted for confounding variables using intention to treat analysis with imputation of missing values.

Detailed Description
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There is a bidirectional involvement between the chronic kidney disease (CKD) and sleep apnea syndrome (OSAS). The declining of renal function, the fluid overloading and the disturbance of ventilation control could cause sleep apneas. On the other hand, the nocturnal hypoxia in patients with OSAS has been associated with changes in the renin-angiotensin system and sympathetic nervous system and production of reactive oxygen species. These findings are relationed with the deterioration of kidney function.

Official Title
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Effect of CPAP in the Worsening of Renal Function in Early Stages of Chronic Kidney Disease (CKD)

Conditions
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Chronic Kidney Insufficiency, Sleep Apnea

Intervention / Treatment
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* Device: CPAP
* Other: conservative treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients referred to the outpatient nephrology department with a diagnosis of chronic kidney disease stages G1-3 KDIGO Older than18 years Habitual snoring or observed apneas Scale sleep sleepiness (Epworth Test) with 11 points or lower. Exclusion Criteria: Very debilitating chronic or neoplastic disease Respiratory failure (PaO 2 <55 mm Hg). Other symptoms of suspected sleep disorder different from OSAS. Patients unable to perform self-administered questionnaires. Patients with> 50% of central apnea or Cheyne-Stokes. Patients who do not sign the informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cpap group<br>CPAP treatment plus conservative treatment with lifestyle modifications. | Device: CPAP<br>* continuous positive pressure in the airway<br>|
| Active Comparator: control group<br>Conservative treatment with lifestyle modifications. | Other: conservative treatment<br>* conservative treatment group with lifestyle modifications<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To test whether treatment with CPAP in patients with moderate to severe OSAS and CKD in stages KDIGO G1-3, reduces the progression of renal disease (30% drop in GF) after 2 years of followed up. | Number of participants with chronic kidney disease (CKD) and obstructive sleep apnea syndrome (OSAS) with a 30% decline in estimated glomerular filtration rate (eGFR) using the CKD-EPI (CKD Epidemiology Collaboration) 2009 creatinine equation after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the prevalence of OSAS in patients with CKD stages G1-3 KDIGO | Number of participants with CKD and snoring and observed apneas with an apnea and hypoapnea index (AHI) ≥15/hour in home-based polysomnography. | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| To test whether treatment with CPAP reduces the albumin / creatinine ratio in urine. | Number of participants with CKD and OSAS with a decline in urine albumin to creatinine ratio. | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| To evaluate whether treatment with CPAP reduces serum Cystatin C | Number of participants with CKD and OSAS with a decline in serum cystatin C levels | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| To evaluate whether treatment with CPAP reduces inflammation-endothelial disfunction markers | Number of participants with CKD and OSAS with a decline in inflammation-endothelial disfunction markers (interleukine-6, interleukine-8, reactive C protein, sedimentation rate, asymmetric dimethylaginine or ADMA, intercellular adhesion molecule 1 or ICAM-1, vascular adhesion protein 1 or VCAM 1, vascular endothelial growth factor or VEGF) | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| Evaluate whether treatment with CPAP reduces the progression of CKD to a different stage | number of participants with CKD and OSAS with a change to a higher CKD stage according to eGFR. | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| to test wheather CPAP reduces the percentage of patients achieving replacement therapy | number of participants with CKD and OSAS who need renal replacement therapy (haemodialysis, peritoneal dialysis or renal transplantation) | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| Evaluate wheather treatment with CPAP reduces the incidence of cardiovascular events | number of participants with CKD and OSAS who suffered a cardiovascular event (myocardial infarction, stroke, hospitalization for heart failure, atrial fibrillation) | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| Evaluate wheather treatment with CPAP reduces the mortality | number of participants with CKD and OSAS with CPAP treatment who died (all-cause mortality) | after 2 years of followed up (each patient will be followed up for at least 2 years - range from 2 to 3 years) | 
| Evaluation of the cost-effectiveness of treatment groups with and without CPAP | Cost-effectiveness of treatment groups conducting a cost-effectiveness study that allow us to estimate the incremental cost-effectiveness ratio (ICER) of CPAP treatment group compared to the conventional treatment group | after 2 years of followed up (each patient will be followed up for at least 2 years-range from 2 to 3 years) | 
| Compare the evolution of inflammation-endothelial disfunction markers in NO-OSAS group versus OSAS group | Number of participants with NO-OSAS versus OSAS who have a decline in inflammation-endothelial disfunction markers (interleukine-6, interleukine-8, reactive C protein, sedimentation rate, asymmetric dimethylaginine or ADMA, intercellular adhesion molecule 1 or ICAM-1, vascular adhesion protein 1 or VCAM 1, vascular endothelial growth factor or VEGF) | after 2 years of followed up (each patient will be followed up for at least 2 years-range from 2 to 3 years) | 
| Compare the worsening of the glomerular filtration in NO OSAS group versus OSAS group | number of participants with NO OSAS versus OSAS who have a worsening of the glomerular filtration. | after 2 years of followed up (each patient will be followed up for at least 2 years-range from 2 to 3 years) | 
| Compare the percentage of patients achieving renal replacement therapy in NO OSAS group versus OSAS group | number of participants who need renal replacement therapy in NO OSAS group versus OSAS group | after 2 years of followed up (each patient will be followed up for at least 2 years-range from 2 to 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CPAP, Chronic kidney disease, sleep apnea