Subjects
Nineteen kidney transplant patients with estimated glomerular filtration rate (eGFR) > 30 ml/min and 10 healthy control subjects were included in the study. Patients were recruited from the nephrology outpatient clinic of Turku University Central Hospital during 2017–2018. Our aim was to study microvascular function. Thus, patients with CKD 4 (eGFR < 30 ml/min) and/or with abdominal calcification score (AAC) > 8 and/or with any clinical signs of atherosclerotic disease (CAD, cerebrovascular disease, peripheral artery disease) were excluded. None of the healthy controls had any history of heart or kidney disease or were on any medication.
Myocardial PET
The imaging studies were carried out after a 10-h overnight fast. Caffeine and alcohol were prohibited for 1 day before assessment. Patients were instructed to take their medication as usual at study day except angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB), which were discontinued 3 days before imaging due to renal imaging on the same day.
Venous catheter was placed in an antecubital vein for injection of oxygen-15-labeled water [15O]H2O and adenosine. The subjects were positioned supine in the camera (Discovery 690 PET/CT scanner, GE Medical Systems, Waukesha, Wisconsin, USA). A low-dose helical CT scan with automatic dose modulation (120 kVp, 10–80 mAs, noise index 30, pitch of 1.375, rotation time of 0.5 s) was acquired during normal breathing before the resting PET scan to correct for photon scatter and attenuation. Electrocardiogram (ECG), heart rate (HR), and blood pressure were monitored continuously during the studies.
Rest and stress MP imaging with [
15O]H
20 PET was performed as described earlier [
19]. Oxygen-15-labeled water (470 MBq) was injected (Radiowater Generator, Hidex Oy, Finland) at rest, and simultaneously, a PET perfusion scan was started. The dynamic acquisition scan of 4 min 40 s was performed with corresponding frame times of (14 × 5 s, 3 × 10 s, 3 × 20 s, and 4 × 30 s). After a 10-min decay of the [
15O]H
2O radioactivity, an identical [
15O]H
2O PET (470 MBq) sequence was performed during hyperemia. Adenosine was initiated 2 min before the stress scan for maximal vasodilatation. The mean radiation dose was 1 mSv for the perfusion study.
The PET data were reconstructed using 3D ordered subset expectation maximization (vendor name: VUE Point HD) with point spread function modelling (vendor name: SharpIR) with a 128 × 128 matrix and FOV of 350 mm in size. The reconstructions were performed using 2 iterations, 24 subsets, and a Gaussian post-filter of 6.4 mm. The PET images were reconstructed with all quantitative corrections applied to the reconstructed images, including attenuation, scatter, decay, and random corrections.
Global MP was analyzed with Carimas software [
19,
20]. Arterial input function was extracted directly from the dynamic PET data. Single-tissue compartment model was used with correction for perfusable tissue fraction to generate parametric MP images [
19,
20]. MP was expressed in milliliters per minute per gram of perfusable tissue (ml/min/g).
MPR was calculated as the ratio of stress-to-rest MP. Because basal MP is related to the rate pressure product (RPP), an index of myocardial oxygen consumption, basal MP values were corrected for RPP (systolic blood pressure × HR) by the equation: basal MP
corr = basal MP/individual RPP × average RPP of the healthy controls [
21]. The average RPP of the healthy was used to make comparison of perfusion values between the patients and the healthy controls easier. Corrected MPR (MPR
corr) was defined as the ratio of hyperemic MP divided by basal MP
corr. Coronary vascular resistance (CVR) was calculated as mean arterial pressure (MAP) divided by global MP.
MAP after adenosine administration was calculated as mean of the 3- and 6-min MAP. Stress MP > 2.3 ml/min/g, and MPR > 2.5 were considered normal based on previous validation [
19].
Statistical analysis
Comparisons between healthy controls and kidney transplant patients for continuous parameters were performed with Kruskal–Wallis test. Additional analyses were performed when males and females, diabetic and non-diabetic, were compared. In addition, correlation coefficients were calculated when associations were examined. All statistical tests were performed as two tailed, with a significance level set at 0.05. The analyses were performed using SAS System, version 9.4 for Windows (SAS Institute Inc., Cary, NC, USA).