Intermittent Hypoxia Exacerbates Decreased GFR and Increased Blood Pressure in Rats with Chronic Kidney Disease

Abstract

Kidney injury and sleep apnea (SA) are risk factors for hypertension. This study evaluated interactions between simulated sleep apnea and chronic kidney disease. Rats were exposed to intermittent hypoxia (IH) to simulate SA and were given excess adenine in the diet to cause acute renal injury leading to chronic kidney disease (CKD). We hypothesized that exposing CKD rats to IH would accelerate declines in renal function and increase blood pressure. Male Sprague‐Dawley rats were fed a 0.4% adenine diet or a control diet until plasma urea nitrogen was >140 mg/dL in the adenine group. After two weeks of recovery (normal rat chow for all groups), rats were exposed to IH (20 exposures/hr of 5% O2/5% CO2 7 hr/day) or SHAM for 6 weeks. Arterial pressure (AP) was monitored continuously with indwelling telemeters and plasma and urine samples were collected weekly using metabolism cages to calculate glomerular filtration rate (GFR). AP was increased in rats fed the adenine diet compared to rats on the control diet prior to starting IH. IH treatment further increased AP so that after 6 weeks of Sham or IH treatment AP was elevated in both adenine groups and in the IH only group with pressures in Adenine/IH rats > adenine/Sham rats = Control/IH rats > Control/Sham rats. Histological analysis revealed crystalline deposits and damage to the proximal and distal tubules with interstitial fibrosis in the kidneys of all the adenine fed rats. Fibrosis persisted up to 8 weeks post adenine removal and IH did not cause any apparent additional damage. GFR remained impaired in both the adenine groups throughout the six weeks of IH or SHAM exposures with elevated plasma creatinine levels that were not altered by IH treatment. Therefore simulated SA augments increases in blood pressure in rats with pre‐existing CKD without affecting GFR suggesting that treating apnea should help prevent worsening secondary cardiovascular stresses in CKD patients.Support or Funding InformationNHLBI 123301, Dialysis Clinic Inc. Reserve Fund Grant