Prevention of contrast-induced nephropathy by limb ischemic preconditioning: underlying mechanisms and clinical effects

Abstract

Contrast-induced nephropathy (CIN) is an important complication following diagnostic radiographic imaging and interventional therapy. It results from administration of intravascular iodinated contrast media (CM) and is currently the third most common cause of hospital-acquired acute kidney injury. CIN is associated with increased morbidity, prolonged hospitalization, and higher mortality. Although the importance of CIN is widely appreciated, and its occurrence can be mitigated by the use of pre- and posthydration protocols and low osmolar instead of high osmolar iodine-containing CM, specific prophylactic therapy is lacking. Remote ischemic preconditioning (RIPC), induced through short cycles of ischemia-reperfusion applied to the limb, is an intriguing new strategy that has been shown to reduce myocardial infarction size in patients undergoing emergency percutaneous coronary intervention. Furthermore, multiple proof-of-principle clinical studies have suggested benefit in several other ischemia-reperfusion syndromes, including stroke. Perhaps somewhat surprisingly, RIPC also is emerging as a promising strategy for CIN prevention. In this review, we discuss current clinical and experimental developments regarding the biology of CIN, concentrating on the pathophysiology of CIN, and cellular and molecular mechanisms by which limb ischemic preconditioning may confer renal protection in clinical and experimental models of CIN.

Remote ischemic preconditioning reduces the incidence of contrast‐induced nephropathy in patients undergoing coronary angiography/intervention: Systematic review and meta‐analysis of randomized controlled trials

“…bradykinin, erythropoietin, prostaglandins, nitric oxide, O-linked β-N-acetylglucosamine, and adenosine has been shown to be involved. 25,26 Remote ischemic preconditioning also activates reperfusion injury salvage kinase pathway, endogenous antioxidant system, hypoxia-inducible factor system, suppressing induction of renal inflammation, and preventing renal tubular cell apoptosis. 25 8,15 The sample size for diabetics in the aforementioned study were small and larger trials that assess diabetic patients were needed.…”

tert-Butylhydroquinone Treatment Alleviates Contrast-Induced Nephropathy in Rats by Activating the Nrf2/Sirt3/SOD2 Signaling Pathway

“…The pathogenesis of CIN is not completely known, and therefore, there is no specific treatment for the clinical management of CIN. However, renal parenchymal hypoxia and the generation of reactive oxygen species (ROS) have been reported to play a critical role in the pathogenesis of CIN [4]. Studies based on animal models of CIN have shown that the disturbance of oxygen balance may result in cell apoptosis and necrosis and may manifest as medullary hypoxic injury [5].…”

Limb ischemic preconditioning ameliorates renal microcirculation through activation of PI3K/Akt/eNOS signaling pathway after acute kidney injury

“…The alteration of renal microcirculation due to CM administration is considered a key pathophysiology mechanism of CM-AKI [3]. CM induced a transient and intense renal vasocontraction especially in medulla [23,24].…”

“…higher mortality, in addition to increased caregiver burden and higher financial cost [2]. The prophylactic strategies developed to mitigate CI-AKI are largely restricted to pre-and post-hydration protocols and attempts of pharmacological interventions have been disappointing [3].…”