Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05256004 |
| Other study ID # |
110070 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 1, 2022 |
| Est. completion date |
December 31, 2022 |
Study information
| Verified date |
February 2023 |
| Source |
Tungs' Taichung Metroharbour Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Background:
Peripheral arterial disease (PAD) a condition characterized by atherosclerotic occlusive
disease of the lower extremities is commonly observed in patients with chronic kidney disease
(CKD) patients, particularly those on dialysis. We conducted detailed biomarkers such as
thrombospondin and related inflammatory biomarkers for the risk of developing and presence of
PAD. Thrombospondin-4 (TSP-4) is an extracellular matrix protein of the vessel wall. Despite
bench evidence, its significance in the clinical setting of chronic kidney disease (CKD) is
missing
Methods:
This is a cross-sectional, single-center study. A cohort of 450 patients aged 20 or over, who
have been on HD for at least 3 months prior to enrollment (Dec 1, 2021) will be included.
TSP-4 and TSP-1 will be measured in HD patients using a commercially available ELISA. PAD is
diagnosed by the ankle-brachial index (ABI) We will measure related blood biomarkers such as
serum hs-cTnT, N-terminal probrain natriuretic peptide, s-Klotho and FABP-4.
Description:
Study Population and Data Source
This is a cross-sectional, single-center study which will be conducted in the Dialysis Center
of Tungs' Taichung MetroHarbor Hospital (TTMHH) in the coastal region of central Taiwan. A
cohort of 500 patients aged 20 or over, who have been on HD for at least 3 months prior to
enrollment will be included. The medical charts of these patients are reviewed for
eligibility identification, and should be compatible with the inclusion/exclusion criteria
and enrolled in our analysis. The research was conducted ethically in accordance to the World
Medical Association Declaration of Helsinki. Subjects provided written informed consent and
the Local Ethical Committee approved the study.
The baseline data such as demographics, comorbidities, anthropometrics, and relevant
laboratory data, clinical diagnosis of hear failure based on cardiac echocardiograhy
measurements, and medication history will be collected. None of the patients were receiving
blood transfusions, or intravenous iron therapy within two weeks before the time of
inclusion. Doppler echocardiography using standardized equipment and complying with
recommendations from the American Society of Echocardiography (2009)[20]. The biplane method
of disks was used to measure left ventricular (LV) EF. Patients were eligible for the study
if they had the New York Heart Association (NYHA) functional class II-IV; HFrEF and left
ventricular EF (LVEF)≤40%. The characteristics of patients will be exclude from our study
were (1) decompensated cirrhosis , (2) neoplastic diseases , (3) incomplete data, (4)
receiving hemodialysis < 3 months and active infection.
Iron Status and Other Laboratory Measurements
Blood was drawn with EDTA anticoagulant in the morning after an overnight fast of at least 12
h before a dialysis session. The samples were separated via centrifugation (3000 rpm, 10 min)
and immediately stored at -80°C for subsequent assays. Glucose, high-density lipoprotein
cholesterol HDL), triglycerides and total cholesterol are all measured by standard assays
using the analyzer. Low-density lipoprotein cholesterol (LDL) is measured by standard assay.
High-sensitivity C-reactive protein (hsCRP) and are measured using standard nephelometry.
Serum hs-cTnT was measured using a sandwich immunoassay method, a novel highly sensitive
assay with a lower measurable limit of 3 ng/L.
Iron deficiency was defined using the Kidney Disease Outcomes Quality Initiative guidelines
criteria: ferritin < 100 ng/mL or transferrin saturation (TSAT) < 20% when ferritin is < 800
ng/mL.[21] Serum iron was measured using spectrophotometry; serum ferritin and transferrin
were measured using immunoturbidimetry. The TSAT was estimated using the formula: TSAT serum
iron (μg/dL)/[serum transferrin (mg/dL)×1.25].[22] Additional measures of iron status were:
serum soluble transferrin receptor (sTfR) (measured using an enzyme immunoassay),[23-24] and
ferritin index. Ferritin index has been proposed as a useful tool in the diagnosis of ID
states, where ratios > 2 suggest ID. The ferritin index is calculated by dividing sTfR
(expressed in nmol/L or mg/L) by log10 ferritin (measured in ng/mL) and is thus increased
whenever sTfR is raised and or ferritin is reduced.[25] Hepcidin is a 25-amino-acid peptide
that is produced mainly by the liver, secreted into plasma, and excreted in urine. It is the
main regulator of systemic iron homeostasis which restricts the intestinal iron absorption
and iron release from macrophages [26]. Serum hepcidin was assayed using a hepcidin ELISA
Kit(Human Hepc25), a sandwich-ELISA technique.
Measurement of biomarkers
The GDF15 concentrations are determined by a quantitative sandwich enzyme immunoassay
technique (Quantikine®; R&D Systems, Inc. Minneapolis, MN, USA). Quality control (QC) samples
from R&D Systems, which had a total coefficient of variation (CV) of 6.3% at low
concentrations (159 ng/L), 9.7% at medium concentrations (436 ng/L), and 15.1% at high
concentrations (827 ng/L), were included in each assay and results were accepted when QCs
fell within manufacturer-specified lot-specific concentration. Overall range of GDF15
detection was 308-13790 ng/L. Gal-3 concentration in plasma was analyzed in duplicate by a
commercially available ELISA kit (Norcross, GA or BG Medicine, Inc., Waltham, Mass., USA).
Soluble ST2 levels were assessed on baseline samples using a highly sensitive sandwich
monoclonal immunoassay (Presage® ST2 Assay, Critical Diagnostics, New York, NY), with a lower
limit of detection of 2 ng/mL, an upper limit of detection of 200 ng/mL, an intra-assay
coefficient of variation <2.5%, and an interassay coefficient of variation of<4.6%15. Serum
H-FABP was measured by an enzyme-linked immunosorbent assay (Hycult Biotech, Uden, the
Netherlands). The hsTnT concentrations was measured by electro-chemiluminescence immunoassay
using the troponin T high-sensitivity assays, on a Cobas analyser (Roche Diagnostics GmbH,
Mannheim, Germany or Abott ). Serum NT-pro-BNP was analyzed using a commercial NT-proBNP
ELISA kit. Detection of NT-proBNP ranged from 12 ng/L to 35 000 ng/L and hsTnT ranged between
3 ng/L and 1172 ng/L. All assays were performed in duplicate by technicians blinded to the
all clinical data.
