The study protocol was approved by the Hannover Medical School Ethics Committee (protocol # 3952). Stable adults undergoing chronic hemodialysis treatment were studied after written informed consent was obtained from the patients.
Participants of the Study
Participants included were undergoing chronic hemodialysis for at least one year with a regimen of at three times per week. None of the patients suffered from instable coronary artery disease or had signs of severe heart failure (>NYHA II). The patients had no signs of infections based on c-reactive protein (CRP) and clinical examination. Exclusion criteria were participation in other studies during the previous three month, allergy against contrast agents or iodine, hyperthyroidism or unclear dysfunction of thyroid gland, premenopausal women, history of radiation of the cranium, residual diuresis (≥500 ml/day), history of stroke within six weeks prior to study participation, taking nutrition supplements containing L-arginine, and any further conditions at the discretion of the treating physician.
The study participation took place on the patient’s midweek dialysis day. After measurement of the predialysis body weight, heart rate, blood pressure and body temperature the dialysis needles (17 Gauge, Bionic Medizintechnik, Friedrichsdorf, Germany) were placed as usual in the dialysis fistula and a blood gas analysis (BGA) including determining sodium and potassium was performed.
Afterwards the patient was taken to the computed tomography (CT) scan in supine and resting position, to rule out influences by altered hemodynamics. The initial CT-scan was performed as described below and the patient was taken back to the dialyis unit. The four hour lasting dialysis session was performed using the Genius® (Fresenius Medical Care, Bad Homburg Germany) single-pass batch-dialysis system with a high-flux polysulfone dialyser FX 60 (Fresenius Medical Care, Bad Homburg Germany). The dialysis solution was composed according to the patient’s requirements. The blood flow and the countercurrent dialysate flow ranged between 200 and 250 ml/min, there was no net ultrafiltration. After 4 hours the patients underwent a second pulse wave analysis and subsequently a second CT.
Perfusion CT Imaging Protocol
The method used was described previously and adapted due to modified CT hardware 
. In brief, all perfusion CT imaging examinations were performed at a Lightspeed 16 row helical CT scanner (GE Medical Systems, Milwaukee, Wis.). The position of the scan region was determined from a previously acquired unenhanced baseline CT. Two adjacent slices at the level of the basal ganglia included the vascular territory of the anterior, middle and posterior cerebral artery. During a scan time of 45s the total number of 90 slices for each position with a thickness of 10-mm sections of continuous (cine) scanning (80 kV, 200 mA) were obtained. CT was initiated 4s after injection (injection rate 2.5 mL/s) of iodinated contrast material with an iodine concentration of 400 mg/dl (Imeron 400, Altana, Konstanz, Germany) with a total volume of 40 mL. The contrast agent was injected via one of the placed dialysis needles followed by a saline flush with the same injection rate with a power injector (Stellant Medrad, Indianola, USA). Parametric maps of brain perfusion parameter were created from the resulting tracer kinetic images using commercially available software (Perfusion 3, AW 4.0, GE Healthcare, Milwaukee, USA). This software algorithm computed the regional cerebral blood flow (CBF) in mL/min/100 g brain tissue with the deconvolution of the parenchymal time-concentration curves by a reference arterial input function (AIF). The region of interest (ROI) that provided the AIF was placed in each anterior cerebral artery (to cover bilateral vessels); the venous outflow function ROI placed in the transverse sinus. Total cerebral perfusion was obtained by averaging blood flow from 4 standardized ROIs in each hemisphere as previously described 
Measurement of Pulse Wave Velocity
Carotid-aortic PWV was determined using a validated system (Sphygmocor™; AtCor Medical, Sydney, Australia), which employs high-fidelity applanation tonometry by a pencil-type probe for non-invasive registration of peripheral arterial pressure waves. Pulse waveforms of the common carotid artery and the femoral artery were obtained sequentially and PWV was calculated as the distance between the suprasternal notch and the femoral artery recording site minus the distance between the suprasternal notch and the carotid artery recording site, divided by the time interval between the feet of the flow waves. The device uses the foot-to-foot methods as described previously 
Measurement of Body Temperature
Body temperature was measured with an infrared tympanic thermometer (Genius™ 2, Covidien, Mansfield, MA, USA) with an accuracy of +/−0.1°C.