Oxygen free radicals and contrast nephropathy
Abstract
Ionic, high-osmolality contrast medium causes nephrotoxicity associated with increased intrarenal adenosine production. To test the hypothesis that oxygen free radicals (produced during intrarenal adenosine catabolism to xanthine) should be implicated in the pathogenesis of ionic, high-osmolality contrast medium nephrotoxicity in humans and to determine whether magnesium protects the kidney from oxygen free radical injury following contrast, 39 patients with mild renal dysfunction were divided into low (LoMg++) and normal (NlMg++) magnesium states and randomized to precoronary angiography oral allopurinol (a xanthine oxidase inhibitor) or placebo. Creatinine clearance and urinary xanthine excretion were measured before and after angiography. Forty-eight hours after contrast medium exposure, placebo- treated LoMg++ and NlMg++ patients had 61%+/-5% and 67%+/-6% increases in urinary xanthine excretion, respectively; however, placebo-treated LoMg++ patients had a greater (79%+/-9% v 35%+/-6%; P < 0.01) decrease in creatinine clearance than placebo-treated NlMg++ patients. Allopurinol-treated LoMg++ and NlMg++ patients had no significant change in urinary xanthine excretion, but did have 40%+/-7% and 33%+/- 5% decreases, respectively, in creatinine clearance 48 hours after contrast medium exposure. There was no difference in renal dysfunctional response among placebo-treated NlMg++ patients or allopurinol-treated LoMg++ or NlMg++ patients. These data suggest (1) that oxygen free radicals contribute to ionic, high-osmolality contrast medium nephrotoxicity in hypomagnesemic patients with mild renal disease and (2) that magnesium attenuates the nephrotoxicity mediated by oxygen free radicals. (Am J Kidney Dis 1998 Jul;32(1):64-71)
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Contrast-induced nephropathy: Can we better predict and prevent it?
2021, Revista Portuguesa de CardiologiaInhibition of xanthine oxidoreductase protects against contrast-induced renal tubular injury by activating adenosine monophosphate-activated protein kinase
2019, Free Radical Biology and MedicineReactive oxygen species (ROS) play a pivotal role in the development of contrast-induced nephropathy (CIN). The inhibition of xanthine oxidoreductase is known to reduce levels of ROS. We investigated whether febuxostat could attenuate oxidative stress via the activation of adenosine monophosphate-activated protein kinase (AMPK) against CIN. In a mouse model of CIN, renal impairment and tubular injury substantially increased, whereas febuxostat attenuated renal injury. Plasma and kidney xanthine oxidoreductase levels were decreased by febuxostat. Febuxostat administration was accompanied by the upregulation of AMPK phosphorylation and the inhibition of nicotinamide-adenine dinucleotide phosphate oxidase (Nox)1 and Nox2, followed by the inhibition of hypoxia-inducible factor-1α (HIF-1α) and heme oxygenase-1 expressions and the suppression of transcription factor forkhead box O (FoxO)1 and FoxO3a phosphorylation. Cell survival was significantly reduced after iohexol administration and febuxostat ameliorated iohexol-induced cell death in proximal tubular (HK-2) cells. Furthermore, febuxostat enhanced AMPK phosphorylation and inhibited Nox1, Nox2, and HIF-1α expression in iohexol-exposed HK-2 cells. Finally, these processes decrease ROS in both in vivo and in vitro models of CIN. AMPK inhibition using small interfering RNA blunted the antioxidative effects of febuxostat in iohexol-treated HK-2 cells. Febuxostat attenuated CIN by modulating oxidative stress through AMPK–NADPH oxidase–HIF-1α signaling.
Prevention of contrast induced nephropathy by ischemic preconditioning in patients undergoing percutaneous coronary angiography
2018, Egyptian Heart JournalContrast-induced nephropathy (CIN) is the acute deterioration of renal function after parenteral administration of radio contrast media in the absence of other causes. The true incidence of CIN varies because of differences among the published studies in the definition of CIN, the proportion of high-risk patients, the types of contrast media, and the use of preventive measures. Remote ischemic preconditioning (IPC) may offer a non-pharmacological prevention strategy for lowering CIN in patients undergoing coronary procedures. The assumption that IPC produces protective effects on tissues or organs by multiple brief cycles of ischemia and reperfusion applied to another remote tissue or organ.
To investigate the effect of ischemic preconditioning in prevention of CIN in patients with renal impairment undergoing percutaneous coronary angiography.
In this study, 100 patients undergoing elective PCI with a base line creatinine clearance <60 ml/min were studied. Patients were divided into two equal groups (ischemic preconditioning group and control group). The incidence of CIN was markedly lower in ischemic preconditioning group 14% VS 38% in control group. The incidence of CIN difference as was found to be (24%). Amount of dye used, decreased LVEF and presence of a significant LAD lesion were significant risk factors for occurrence of CIN.
The current study showed that remote ischemic preconditioning plays an important role in prevention of CIN in patients undergoing PCI with renal impairment GFR < 60 ml/min. The amount of contrast, decreased LVEF, and presence of LAD significant lesion were significant risk factors for developing of CIN and these subgroups benefited from application of ischemic preconditioning.
The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study (EURO-CRIPS CardioGroup I): A randomized controlled trial
2018, International Journal of CardiologyThe potential protective effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) remain to be defined.
A double blind, randomized, placebo controlled multicenter study was performed. Patients younger than 85 years old, with a renal clearance of 30–60 ml/min/1.73 m2, who were candidates for PCI for all clinical indications except for primary PCI, were allocated 1:1 to RIPC or to standard therapy. The primary endpoint was incidence of CIN. The secondary endpoint was incidence of peri-procedural myocardial infarction (PMI). From February 2013 to April 2014, 3108 patients who were scheduled for coronary angiography were screened for the study. 442 fulfilled the inclusion criteria and 223 received PCI. These patients were randomized to sham RIPC (n = 107) or treatment group (n = 116). The only pre-specified subgroup of diabetic patients included 85 (38%) cases. RIPC significantly reduced CIN incidence in the overall population (12.1% vs. 26.1%, p = 0.01, with a NNT = 9) and in non-diabetic patients (9.2% vs. 25.0%, p = 0.02), but showed no benefit in diabetics (16.7% vs. 28.2%, p = 0.21). A trend for lower PMI was seen in the intervention arm (creatine kinase - muscle brain > 5 URL; 8.4% vs. 16.4%, p = 0.07; troponin T > 5 URL; 27% vs. 38%, p = 0.21).
Remote ischemic preconditioning significantly reduces the incidence of acute kidney injury in non-diabetic patients undergoing PCI. Larger sample size is presumably needed to assess the effect of RIPC for patients with diabetes mellitus.
Clinical Trial number: NCT02195726 https://www.clinicaltrial.gov/.
Contrast-Induced Nephropathy and Oxygen Pretreatment in Patients With Impaired Renal Function
2018, Kidney International ReportsContrast-induced nephropathy is a complication following coronary angiography and percutaneous coronary intervention. Because contrast-induced nephropathy is a predictor of long-term mortality in patients with ischemic heart disease undergoing percutaneous coronary intervention, preventive strategies are required. We assessed the effects of periprocedural oxygenation on contrast-induced nephropathy among patients with pre-existing renal dysfunction.
A total of 200 consecutive patients with impaired renal function (estimated glomerular filtration < 60 ml/min per 1.73 m2) undergoing elective cardiovascular angiography were randomly assigned to an oxygenation treatment (n = 100) or control group (n = 100). In oxygenation treatment, pure oxygen (2 L/min) was administered for 10 minutes before exposure to contrast medium. The primary endpoint was the incidence of contrast-induced nephropathy, defined as a ≥ 25% increase in serum creatinine levels from baseline within 48 hours of exposure.
In the oxygenation treatment group, partial pressure of arterial oxygen was higher (135 ± 25 mm Hg vs. 84 ± 10 mm Hg, P < 0.001); contrast-induced nephropathy incidence was lower (1% vs. 8%, odds ratio [OR] = 0.12, 95% confidence interval [CI] = 0.01–0.95, P = 0.02); and partial pressure of arterial carbon dioxide and bicarbonate base lactate levels were similar compared with those in the control group. Upon univariate analysis, excess and absence of oxygenation treatment (OR = 9.18, CI = 1.13–74.86, P = 0.03) and anemia (OR = 4.30, CI = 1.04–17.78, P = 0.04) were shown to be associated with contrast-induced nephropathy incidence.
Oxygenation, a simple, nonpharmacological strategy, may be beneficial when using contrast media in patients with impaired renal function from noninvasive angiography to emergency catheterization.
Usefulness of Sodium Bicarbonate for the Prevention of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Resynchronization Therapy
2017, American Journal of CardiologyThe use of contrast media during cardiac resynchronization therapy (CRT) devices implantation is associated with the risk of contrast-induced nephropathy (CIN). The aim of this study was to evaluate the possible beneficial role of periprocedural intravenous volume expansion with isotonic saline and sodium bicarbonate solution in patients who undergo CRT implantation. Eligible patients were randomly assigned in a 1:1 ratio to receive hydration plus one-sixth molar sodium bicarbonate (study group) or not (control group). Primary end point was CIN incidence. Secondary end points were (1) a combined end point of death, heart transplantation, or hospitalization for heart failure at 12 months, (2) incidence of death, and (3) the need for renal replacement therapy at 12 months. Final analysis was performed with 93 patients. In the hydration group CIN incidence was significantly reduced related to control group (0% vs 11%, p = 0.02). There was a trend to reduce the combined end point in hydration group (12.5% vs 22%, p = 0.14). Finally, CIN incidence was related to a higher 12 months mortality (25% vs 7%, p = 0.03). In conclusion, CIN incidence was 11% in a nonselected population of patients receiving a CRT device. CIN appearance could be reduced by using a hydration protocol based on sodium bicarbonate and isotonic saline.