DiscussionThe present studydemonstrates that remote IPC, induced by intermittent upper-arm ischemia beforean invasive coronary procedure, reduces the incidence of contrastmedium–induced nephropathy in patients with chronic kidney disease and highrisk for CI-AKI. This protective effect appeared to be independent of all otherfactors, eg, contrast medium amount and comorbidities of the patients.
CI-AKI is a frequent andserious complication after CA with or without percutaneous coronaryintervention. Moreover, CI- AKI has been shown to be an independent predictorof 1-year mortality in patients with coronary artery disease. The incidence ofCI-AKI varies substantially among several studies because of the lack of auniform definition of CI-AKI.(16,96) Rates of CI-AKI may be as high as >50%, depending on thepresence of risk factors such as chronic renal insufficiency and diabetesmellitus or heart failure.(4,16–18) To date, there is noeffective prophylactic regimen to prevent CI-AKI. Dopamine, fenoldopam,furosemide, mannitol, aminophylline, atrial natriuretic peptide, captopril, calciumchannel blockers, and alprostadil were not effective in reducing the incidenceof CI-AKI (97–100) Initial studies assessing the ability of NAC to prevent CI-AKIwere encouraging; however, the role of NAC in prevention of CI-AKI has beenquestioned, because subsequent larger trials failed to demonstrate anNAC-associated benefit.
(101,102) Likewise, there are inconsistent data on the effects of NAC onserum creatinine. In healthy volunteers with normal renal function and noexposure to contrast medium, there was a small but significant decrease in meanserum creatinine and urea concentrations and a significant increase in eGFR. (103) Levels of cystatin C remained unchanged after NAC administration.However, no change in serum creatinine or cystatin C was observed in patientswith chronic kidney disease.(104,105) Our hypothesis that IPC maybe nephroprotective was largely based on earlier reports showing the beneficialaction of IPC in several clinical settings. IPC has been reported to decreasethe incidence of perioperative myocardial injury during cardiac surgery inadults (63,106,107) and children(108) and to diminish both myocardial and renal injury incidence duringsurgery for endovascular (109) and open surgical(110) repair of abdominal aortic aneurysm.
Very recently, IPC beforehospital admission has been shown to increase myocardial salvage by attenuationof reperfusion injury in patients with evolving myocardial infarction.(111) Given the results of thepresent study, a novel concept of cytoprotection by IPC before CA may beconsidered for the prevention of CI-AKI in numerous patients. Moreover, IPC canbe applied easily, and virtually no safety concerns exist if it is performedappropriately.
Even if the underlying mechanisms of IPC- mediated beneficialeffects remain largely unknown, the noninvasive IPC protocol is likely to havedirect effects on decreasing renal ischemia/reperfusion injury incidence aspart of the systemic protective effect of this phenomenon. It has been postulated thata remote organ releases humoral factors such as adenosine or bradykinin intothe systemic circulation, which subsequently protect the remote region ororgan. Other underlying mechanisms may include erythropoietin, activation ofthe KATP channel, nitric oxide, delta 1-opioid, and free radicals.
(78) Some studies have also suggested that the protective effect ofIPC may be caused by its beneficial anti-inflammatory or antioxidant effectsand decreased extracellular levels of noxious metabolites, such as protons andlactate.(78,83) Additionally, some other studies have favored a neurogenicpathway.(112) Overall, our conceptsuggests a humoral basis for the underlying renoprotective effects, because inthe additional experimental setting, we found elevated erythropoietin plasmalevels and mRNA expression in a reperfusion ischemia mouse model (V. Burst etal, 2012). It is well known that reperfusion injury involves several pathways,including alterations in cellular metabolism, endothelial dysfunction,inflammation, hypercontracture, and necrosis/apoptosis.
(113) Thus, IPC-mediated counterregulatory protective pathways may eventuallyoffer an additional clinical benefit and contribute to better clinical outcomes This study was carried out from March2016 to September 2017 at a tertiary care hospital. Two groups of patients (both males andfemales) who were diagnosed cases of CKD stage 3 & 4 and admitted forelective angiography were included in the study. One group received hydration, N-acetylcysteine andsham preconditioning (Control Group) and the other group received hydration, N-acetylcysteine andremote ischemic preconditioning (IPC Group). A total of 147 patients were assessed for eligibility, but 36 did not fulfillthe inclusion criteria, and 24 did not agree to the protocol. A total of 87patients were included. Of these patients, 42 were randomly allocated toreceive standard therapy (control group) and 45 to receive standard therapyplus IPC (IPC group). 7 patients in control group and 5 patients in IPC grouplost for 6 weeks follow-up.(Figure: 12) In 2004, Mehran et al (17) developed a risk classification system to predict risk forcontrast medium–induced nephropathy in patients undergoing CA.
This mostcomprehensive and best-validated risk stratification score includes clinicaland procedural variables and is divided into 4 classes of risk of developingCI-AKI: Low (risk score <5), moderate (risk score 6–10), high (risk score11–15), and very high (risk score ?16). The calculated mean integer score forboth groups in the present study was 8.33±2.
3 and 8.22±1.94 p=0.
808(Table: 10 )thus determining the present study population as a group at moderate risk ofdeveloping CI-AKI (>80% of thesubjects were at moderate risk). In our study incidence of CIAKI is 19.04% inthe control arm of the study is within the reported range and corresponds tothe serum creatinine–based CI-AKI incidence predicted by Mehran et al.
(17) In this study, the primary study end point, contrast medium inducednephropathy, occurred in 8 patients (19.04%) in the control group and 2 (4.4%)in the IPC group (odds ratio in univariable analysis, 0.1977, 95% confidenceinterval, 0.0394 to 0.9924; P=0.
048).(Table:12)Serumcreatinine was similar in both groups at baseline (control group 2.14± 0.44,IPC group 2.16±0.
46 mg/dl) but increased significantly more after 48 hours incontrol group (control group 2.36±0.75mg/dl)compared with patients in IPC Group (IPC group 2.01±0.54mg/dl) (p=0.016).(Table:13)Similar results were obtained by Er et al.
(2012) RenPro trial.(56) This study included 100 adults (mean age 73.2years) with impaired renal function (serum creatinine 124 mmol/L and/or eGFR,60ml/min per 1.73 m2; mean Mehran score 13) who underwent elective coronaryangiography. The primary study outcome, CI-AKI (defined as a serum creatinineincrease of .44 mmol/L or a relative increase of ?25%f from baseline within 48hours after exposure to contrast medium), occurred in significantly fewerpatients in the rIPC group than in the control group (12% versus 40%; P=0.002).No major adverse events related to the procedure were reported.
Overall, therewas a substantial decrease in the number of patients developing CI-AKI inindividuals who received rIPC before coronary angiography, suggesting that rIPCwas particularly renoprotective in high-risk patients