Consecutive Incident Adult Patients Undergoing Elective Cardiac Surgery Clinical Trial
Official title:
The Diagnostic Role of Cystein-rich Protein 61 (Cyr61) in Acute Kidney Injury: Correlation With the Harmonic Analysis of Arterial Pressure Pulse Waves.
Acute kidney injury (AKI) is a common heterogeneous disease that complicates several medical
and surgical conditions. Recent studies have demonstrated that the occurrence of AKI
significantly increase the risk of adverse outcomes. Despite the advanced in modern
medicine, the interventions for AKI are not improved. One major reason of the failure to
shift therapeutic progress is the clinicians' widespread dependence upon serum creatinine,
an unreliable marker during acute changes of renal function, for the diagnosis of AKI.
In the past decade, over 20 unique biomarkers of AKI had been explored. Among them,
neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury
molecule-1 (KIM-1) have received the most interest. None of them, however, is an idea one.
Cysteine-rich protein 61 (Cyr61), a secreted matrix-associated heparin-binding protein,
belongs to the "CCN" family. It regulates a broad spectrum of cellular activities, including
cell adhesion, migration, proliferation, survival, differentiation, apoptosis, angiogenesis,
and extracellular matrix production of multiple cell types. By the kidney
ischemic/reperfusion injury animal model, Cyr61 gene was found to be rapidly up-regulated in
the renal outer medulla. That portion of the kidney is corresponding to the area of
marginally oxygenated under normal condition and most tubular injury following renal
ischemic/reperfusion injury.18 Elevation of Cyr61 protein was detected in the kidney and
also in urine following injury, making it a potential marker of AKI.
Additionally, pulse diagnosis is an integrative part of traditional Chinese medicine. With
spectral analysis of the pulse waves, researchers started to observe the pulse wave
harmonics. An in vivo study of rats revealed that ligating one or both of the renal arteries
significantly reduced the second harmonic component of the pressure pulse at the caudate
artery. Ligating the artery toward the spleen prominently reduced the third harmonics
component of the pulse. Analysis of the harmonics in the spectrum of the arterial pressure
wave revealed that individual organs might have their own natural frequencies. These
observations suggested that individual vascular beds exert independent, frequency-specific,
effects on the peripheral pressure wave.
Among different etiologies, cardiac surgery is an important cause of AKI. It has been shown
that AKI after cardiac surgery is relatively highly prevalent and prognostically important.
Cardiac surgery is usually performed with the use of extracorporeal cardiopulmonary bypass
machine ('on-pump').
Based on the evidence from cell culture study and animal study in the literature, we
hypothesize that Cyr61 is rapidly increased in the urine after AKI. We thus design this
project to evaluate study the diagnostic role and clinical application of Cyr61 in AKI. We
will conduct a prospective cohort study to evaluate the changes of urinary Cyr61 in patients
undergoing cardiac surgery. Cyr61 may serve a good biomarker for the early diagnosis of
patients with AKI, either singly or in combination with NGAL. By the way, we also try to
correlate the changes in those biomarker with a potential new tool：harmonic analysis of
arterial pressure pulse waves. We have special interest in following the time course of
changes in biomarker and correlate with changes in pulse analysis. Physiological parameters
of vascular compliance and regional blood oxygen saturation will be correlated concurrently.
It is hoped that early detection of AKI will lead to earlier intervention, thus enhancing
our ability to develop beneficial therapies.
| Status | Active, not recruiting |
| Enrollment | 150 |
| Est. completion date | |
| Est. primary completion date | June 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 20 Years to 80 Years |
| Eligibility |
Inclusion Criteria: All consecutive incident adult patients undergoing elective cardiac surgery (including coronary artery bypass graft, valve surgery, and correction of congenital heart diseases) Exclusion Criteria: age younger than 20 years or older than 80 years; pregnant woman; emergent cardiac surgery; use of intra-aortic balloon pump or extracorporeal membrane oxygenation after surgery, pre-existing severe renal insufficiency (defined as estimated glomerular filtration rate 15 cc/min or less by the Modification of Diet in Renal Disease study equation36); patients with end-stage renal disease under maintenance hemodialysis, peritoneal dialysis, or receiving kidney transplantation; use of radiocontrast =24 h prior to the surgery; use of nephrotoxic drugs before or during the surgery |
Observational Model: Cohort, Time Perspective: Prospective
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| National Taiwan University Hospital |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Acute kidney injury | development of AKI within 1 week after cardiac surgery | 1 week after cardiac surgery | No |