Introduction:
Acute kidney injury (AKI) after coronary artery bypass graft surgery (CABG) is a common event, causing a wide range of complications from longer hospital and intensive care unit (ICU) stays to increased risks of renal failure and hemodialysis and higher mortality rates . AKI can, therefore, worsen the outcome of CABG and play a role in dependence on hemodialysis . On the other hand, CABG itself is usually performed in high-risk patients and is the main cause of AKI. With respect to CABG, operation duration and aortic cross-clamp time are some of the proven risk factors for AKI.
The pathophysiology of AKI in the context of CABG can be divided into 3 categories: preoperative, intraoperative, and postoperative. The preoperative factors comprise heart failure, multiple ischemia, medications angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, contrast agents, antibiotics, vasopressors, vasoactive and other nephrotoxic drugs, anemia,4 and preoperative blood transfusion . The intraoperative factors are comprised of the hemodynamic effects of cardiopulmonary bypass (CPB) pump, cytokine and chemokine expression, inflammatory mechanisms, microscopic and macroscopic emboli, effects of aprotinin, and effects of the on-pump technique . And finally, the postoperative factors consist of vasoactive drug use, contrast agents, hypovolemia, sepsis, postoperative heart failure , and re-exploration.
Remote ischemic preconditioning (RIPC) is a phenomenon in which brief ischemia of one organ or tissue provokes a protective effect, which can reduce the mass of infarction caused by vessel occlusion and reperfusion . In CABG surgery, cardiomyocyte injury caused by myocardial protection failure is predominantly responsible for the adverse outcomes. RIPC have been shown to reduce the troponin release 24 h postoperatively in children undergoing corrective surgery for congenital heart disease . Other studies have demonstrated that RIPC using brief ischemia and reperfusion of the upper limb could reduce myocardial injury in adult patients undergoing CABG surgery .
The pathophysiology of AKI is complex and still incompletely understood. New evidence suggests that adaptive responses by tubular epithelial cells to injurious signals are responsible for renal dysfunction and that renal inflammation and microcirculatory dysfunction further amplify these mechanisms. Remote ischemic preconditioning induces the release of various molecules that appear to mediate the protective effect of this intervention.Here, we demonstrate that these mediators might be inducing G1 cell-cycle arrest in the kidney, as indicated by increased urinary Tissue inhibitor of metalloproteinases 2 (TIMP-2) × Insulin like growth factor binding protein 7 (IGFBP7) after remote ischemic preconditioning. Cell-cycle arrest has been implicated in acute kidney injury, and urinary (TIMP-2) × (IGFBP7) has been shown to be predictive of acute kidney injury in patients undergoing cardiac surgery, as well as in general intensive care unit populations.However, cell-cycle arrest is a self-defense mechanism. When exposed to stress, epithelial cells may enter a short period of G1 cell-cycle arrest15 until the danger has passed or injury has been repaired. High-mobility group box-1(HMGB-1) is an endogenous damage-associated molecular pattern molecule that can serve as an early mediator in the context of sterile inflammation, with release occurring as a consequence of acute cellular stress, hypoxia, or necrosis.Extracellular HMGB-1 can bind to several pattern recognition receptors, including Toll-like receptors, which can directly or indirectly induce cell-cycle arrest. Preconditioning with recombinant HMGB-1 provides protection against acute kidney injury. It is hypothesized that HMGB-1 (and other damage-associated molecular patterns) is released after remote ischemic preconditioning and these molecules induce cell-cycle arrest in tubular epithelial cells. Increases in urine (TIMP-2) × (IGFBP7) immediately after remote ischemic preconditioning should therefore be protective from subsequent kidney injury induced by cardiac surgery, whereas late increases in these markers (for example, after cardiopulmonary bypass) should herald acute kidney injury.
It has been postulated that a remote organ releases humoral factors such as adenosine or bradykinin into the systemic circulation, which subsequently protects the remote region or organ. Other underlying mechanisms may include erythropoietin, activation of the KATP channel, nitric oxide, delta 1-opioid, and free radicals.Some studies have also suggested that the protective effect of IPC may be caused by its beneficial anti-inflammatory or antioxidant effects and decreased extracellular levels of noxious metabolites, such as protons and lactate. In addition, some other studies have favored a neurogenic pathway.In a review by Dugbartey et al., it was discussed that neural and humoral pathways were activated in RIPC. “Reperfusion injury salvage kinase” (RISK) is a group of pro-survival kinases, which are an important target of RIPC. Endogenous antioxidant systems are also activated. Inhibition of the opening of mitochondrial permeability transition pores is a cellular mechanism in RIPC.
Because of the similarities between the mechanisms of ischemia-reperfusion injury produced by RIPC and those proposed for AKI after CPB , we decided to test the hypothesis that RIPC could prevent AKI in patients undergoing CABG surgery. In this study, we aimed to evaluate the effect of Remote ischemic preconditioning to prevent AKI after CABG and see the occurrence of AKI within the first 72 hours after surgery and on follow up after 30 days.
Methods:
STUDY DESIGN : Interventional and prospective study
INCLUSION CRITERIA :
1.All patients who give their written informed consent
2. High risk for acute kidney injury who undergo cardiac surgery with the use of cardiopulmonary bypass (A Cleveland Clinic Foundation score of 6 or
higher was used to define patients at high risk for acute kidney injury. The score is composed of different risk factors, including patient characteristics, comorbidities, and type of surgery
3 . Patients with age ≥18 to 80 years, who are diagnosed cases of CKD stage III and IV and admitted for elective CABG, will be included in the study.
4. Patients having impaired renal function with elevated serum creatinine of >1.4 mg/dL or reduced eGFR <60 mL/min/1.73 m2, calculated by the CKD-EPI formula: GFR = 141 × min(Scr/κ, 1)α × max(Scr/κ, 1)-1.209 × 0.993Age × 1.018 [if female] _ 1.159 [if black], where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κor 125
5. The patients who did not receive any sedatives or central nervous system depressants prior to cardiac surgery. The patients must be on standard treatment for ischemic heart disease prior to the procedure.
EXCLUSION CRITERIA :
1.All patients who do not give their consent.
2.Acute myocardial infarction up to 7 days before surgery
3.Age younger than 18 years
4. Preexisting acute kidney injury, kidney transplantation, Patients who have an end-stage renal failure with the need for hemodialysis or reduced eGFR <15 mL/min/1.73 m2
5. Pregnancy
6.Peripheral vascular disease affecting the upper limbs
7. Hepatorenal syndrome
8.Drug therapy with sulfonamide or nicorandil (preconditioning-blocking and preconditioning-mimetic medication, respectively).
STUDY DESIGN :
After obtaining approval from the institutional review board , we will perform the study. Consecutive patients will be approached for enrollment during preadmission consultations and provided written informed consent.
Patients will be divided on a 1:1 basis. On the day of surgery, patients will be assigned to undergo either remote ischemic preconditioning or sham remote ischemic preconditioning. Patients, anesthesiologists, staff providing care of the patient, cardiac surgeons, and intensive care physicians will be unaware of treatment assignment.
PROCEDURE :
Anesthesia will be induced according to the standard of care at the centre and maintained with volatile anesthetics because propofol may interfere with remote ischemic preconditioning. According to a recently published review, we will standardize the management of cardiopulmonary bypass as follows: mean arterial blood pressure of 60 to 70 mm Hg, the use of nonpulsatile cardiopulmonary bypass, α-stat acid-base management to regulate carbon dioxide tension, hematocrit values of 25% to 30%, blood glucose levels less than 200 mg/dL, and the use of arterial line filters.
After induction of anesthesia and before skin incision, we will perform remote ischemic preconditioning consisting of 3 cycles of 5-minute inflation of a blood pressure cuff to 200 mm Hg (or at least to a pressure 50 mm Hg higher than the systolic arterial pressure) to one upper arm, followed by 5-minute reperfusion with the cuff deflated. In patients assigned to the control group, sham remote ischemic preconditioning intervention will be induced by 3 cycles of upper limb pseudo ischemia (low pressure, 5-minute blood pressure cuff inflation to a pressure of 20 mm Hg and 5-minute cuff deflation). The surgical procedure and perioperative care will be performed according to the standard at the center.
Results:
We are conducted a pilot study and so proposed to recruit a total 60 patients (30 patients of Remote ischemic preconditioning and 30 patients of sham conditioning).
Statistical Analysis Data was analysed using SPSS V15.0 (Statistical Package for Social Sciences, Version 15.0) package . Comparison of means of 2 groups wias ,carried out by Student’s unpaired t test for numerical normal data and by Mann Whitney U test for abnormal data. Fisher Exact Probability tests was applied to compare percentages for categorical data between 2 groups. Chi square test was applied to compare percentages of more than 2 groups. All statistical tests will be two tailed. Alpha (α) Level of Significance will be taken as P<0.05.
Out of the 30 patients who underwent sham conditioning , 20 (66.66%) had developed acute kidney injury whereas out of 30 patients who underwent ischemic pre – conditioning , 14 (46.66%) developed acute kidney injury.
Conclusions:
In conclusion , in the present study , we demonstrate that RIPC reduces the incidence of AKI among adult patients undergoing CABG with CPB. Moreover , these benefits offered by RIPC were found to be associated with definition of AKI. In addition , we also conclude that RIPC performed with total duration of ischemia < 20minutes renders the best benefit. However , due to the major limitations of the small sample size and variations of the surgical procedures and basal characteristics of the participants in this study , our conslusions need to be further corroborated in future larger studies.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.