Effects of Sleep Apnea in Chronic Kidney Disease

Patients with chronic kidney disease (CKD) have increased incidence of sleep apnea compared to those without renal disease. We hypothesized that the hypoxia of sleep apnea accelerates declines in renal function and so might contribute to this association. In our model of CKD (0.4% adenine diet for 3 to 5 weeks), rats developed crystalline nephropathy and elevated blood urea nitrogen (BUN) values (> 140 mg/dl). After return to a normal rat diet, BUN decreased to a stable but still elevated level of 50–70 mg/dl simulating CKD (normal rat BUN = 20 mg/dl). 24‐hour urine volumes were also significantly elevated (CKD = 38±3 vs Control = 9.4±0.5 ml). Urinary protein excretion increased in the adenine diet rats but not in the control diet rats. Rats were then exposed during their sleep period to either intermittent hypoxia (IH) to simulate sleep apnea or sham conditions for six weeks. At the end of the IH or sham exposures, BUN levels were greater in CKD rats exposed to IH compared to Sham conditions (Sham = 78.3±3.7 vs. IH = 91.5±3.1 mg/dl) but were not different in non‐CKD groups. Creatinine clearance was lower in rats exposed to IH for both CKD rats (Sham = 1.0±0.2 vs. IH = 0.81±0.1 ml/min) and in control rats (Sham = 4.2±0.7 vs. IH = 1.6±0.1 ml/min) suggesting IH impairs glomerular function. Histological analysis of kidney sections revealed fibrosis and infiltrates in the regions of the proximal and distal tubules with effaced proximal tubules and decreased total number of tubules in all adenine fed rats. This damage persisted 8 weeks after cessation of the diet, independent of sham or IH exposure. Therefore, an adenine diet causes sustained CKD even after the diet is discontinued that results in polyuria and proteinuria. Exposure to IH further compromises renal function suggesting treating sleep apnea in CKD patients should help to preserve renal filtration function.Support or Funding InformationDialysis Clinic, Inc. (DCI)