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Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis.
Woolen, SA, Shankar, PR, Gagnier, JJ, MacEachern, MP, Singer, L, Davenport, MS
JAMA internal medicine. 2020;(2):223-230
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Abstract
IMPORTANCE Risk of nephrogenic systemic fibrosis (NSF) to individual patients with stage 4 or 5 chronic kidney disease (CKD; defined as estimated glomerular filtration rate of <30 mL/min/1.73 m2) who receive a group II gadolinium-based contrast agent (GBCA) is not well understood or summarized in the literature. OBJECTIVE To assess the pooled risk of NSF in patients with stage 4 or 5 CKD receiving a group II GBCA. DATA SOURCES A health sciences informationist searched the Ovid (MEDLINE and MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citation, and Daily and Versions), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Open Grey databases from inception to January 29, 2019, yielding 2700 citations. STUDY SELECTION Citations were screened for inclusion in a multistep process. Agreement for final cohort inclusion was determined by 2 blinded screeners using Cohen κ. Inclusion criteria consisted of stage 4 or 5 CKD with or without dialysis, administration of an unconfounded American College of Radiology classification group II GBCA (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, or gadoteridol), and incident NSF as an outcome. Conference abstracts, retracted manuscripts, narrative reviews, editorials, case reports, and manuscripts not reporting total group II GBCA administrations were excluded. DATA EXTRACTION AND SYNTHESIS Data extraction was performed for all studies by a single investigator, including publication details, study design and time frame, patient characteristics, group II GBCA(s) administered, total exposures for patients with stage 4 or stage 5 CKD, total cases of unconfounded NSF, reason for GBCA administration, follow-up duration, loss to follow-up, basis for NSF screening, and diagnosis. MAIN OUTCOMES AND MEASURES Pooled incidence of NSF and the associated upper bound of a 2-sided 95% CI (risk estimate) for the pooled data and each of the 4 group II GBCAs. RESULTS Sixteen unique studies with 4931 patients were included (κ = 0.68) in this systematic review and meta-analysis. The pooled incidence of NSF was 0 of 4931 (0%; upper bound of 95% CI, 0.07%). The upper bound varied owing to different sample sizes for gadobenate dimeglumine (0 of 3167; upper bound of 95% CI, 0.12%), gadoterate meglumine (0 of 1204; upper bound of 95% CI, 0.31%), gadobutrol (0 of 330; upper bound of 95% CI, 1.11%), and gadoteridol (0 of 230; upper bound of 95% CI, 1.59%). CONCLUSIONS AND RELEVANCE This study's findings suggest that the risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely less than 0.07%. The potential diagnostic harms of withholding group II GBCA for indicated examinations may outweigh the risk of NSF in this population. TRIAL REGISTRATION PROSPERO identifier: CRD42019123284.
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Pharmacologic Prophylaxis of Contrast-Induced Nephropathy.
Toso, A, Leoncini, M, Maioli, M, Bellandi, F
Interventional cardiology clinics. 2020;(3):369-383
Abstract
Different pharmacologic agents have been tested in the effort to prevent contrast-induced acute kidney injury (AKI) in the last two decades. To date, however, no individual drug has received unanimous approval for this aim. Since 2014 statins have been included as preventive treatment in the European guidelines for revascularization procedures in cardiac patients. The present update presents the latest findings in this field focusing on the changing paradigms in the definition and consequently the approach to nephroprotection that considers clinical prognosis as the major issue. We note the current shift from attention to contrast-induced AKI to contrast-associated AKI.
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Contrast-Induced Acute Kidney Injury-Definitions, Epidemiology, and Implications.
Azzalini, L, Kalra, S
Interventional cardiology clinics. 2020;(3):299-309
Abstract
Contrast-induced acute kidney injury (CI-AKI) is the acute onset of renal injury following exposure to iodinated contrast media. Several definitions have been used, which complicates the estimation of the epidemiological relevance of this condition and comparisons in outcome research. The incidence of CI-AKI increases as a function of patient and procedure complexity in coronary, endovascular, and structural interventions. CI-AKI is associated with a high burden of short- and long-term adverse events, and leads to increased healthcare costs. This review will provide an overview of the definitions, epidemiology, and implications of CI-AKI in patients undergoing coronary, endovascular, and structural catheter-based procedures.
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Efficacy of nicorandil on the prevention of contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention.
Zhang, X, Yang, S, Zhang, P, Fu, N
Coronary artery disease. 2020;(3):284-288
Abstract
OBJECTIVES The purpose of this study was to explore the effect of nicorandil on the incidence of contrast-induced nephropathy in patients with coronary heart disease undergoing percutaneous coronary intervention. METHODS This study randomized 300 patients undergoing percutaneous coronary intervention to receive conventional treatment in the control group (hydration only; n = 150) vs. nicorandil therapy (nicorandil 10 mg three times daily plus hydration; n = 150). The primary endpoint was the incidence of contrast-induced nephropathy, defined as rise in serum creatinine ≥44.2 μmol/L or >25% above baseline within 72 hours after exposure to contrast administered during percutaneous coronary intervention. Secondary endpoints included differences in post-percutaneous coronary intervention serum creatinine, blood urea nitrogen, creatinine clearance rate, cystatin-C, and occurrence of major adverse events. RESULTS Contrast-induced nephropathy incidence was 3.3% (5/150) in the nicorandil group vs. 10.7% (16/150) in the control group (P < 0.05). At 48 and 72 hours after contrast administration, cystatin-C levels were significantly lower and creatinine clearance rate were significantly higher with nicroandil therapy compared to conventional treatment (all P values <0.05). No statistical difference was observed in the incidence of major post-procedure side effect events in hospital and fourteen days of follow-up period between the nicorandil group and control group (3.3% vs. 4.0%, P > 0.05). CONCLUSION Compared to conventional treatment, oral nicorandil therapy was associated with less contrast-induced nephropathy and improved renal function following contrast administration during percutaneous coronary intervention.
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Beneficial effect of statin on preventing contrast-induced acute kidney injury in patients with renal insufficiency: A meta-analysis.
Cho, A, Lee, YK, Sohn, SY
Medicine. 2020;(10):e19473
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Abstract
BACKGROUND Renal insufficiency is an important predictor of contrast-induced acute kidney injury (CI-AKI). We performed a meta-analysis to examine the effects of short-term statin therapy on the incidence of CI-AKI, particularly in patients with renal insufficiency. METHODS A systematic search was conducted to retrieve randomized controlled trials (RCTs) that investigated the impact of statin pretreatment before administration of contrast media on the development of CI-AKI in patients with mild to moderate renal insufficiency. The primary outcome was development of CI-AKI. The secondary outcome was the incidence ofacute kidney injury requiring hemodialysis. RESULTS Data analysis from 8 RCTs, which included a total of 2313 subjects in the statin-treated group and 2322 in the control group, showed that statin pretreatment was associated with significant reduction of the risk of CI-AKI (relative risk [RR] = 0.59; 95% confidential interval [CI] 0.44-0.79; P = .0003, I = 0%). A beneficial effect of statin on preventing CI-AKI was consistent, regardless of the dose of statin and use of N-acetylcysteine. In subgroup analysis based on baseline estimated glomerular filtration rate (eGFR), patients with baseline eGFR <60 mL/min/1.73 m (RR = 0.63; 95% CI 0.41-0.98; P = .04, I = 0%) and 30 < eGFR < 90 mL/min/1.73 m (RR = 0.56; 95% CI 0.39-0.82; P = .003, I = 0%) showed significant reduction of risk of CI-AKI. CONCLUSION Statin pretreatment is effective at preventing CI-AKI and should be considered in patients with preexisting renal insufficiency.
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Contrast circulation in adult fontan patients using MR Time Resolved Angiography: Application for CT pulmonary angiography.
Duerden, L, Abdullah, H, Lyen, S, Manghat, N, Hamilton, M
Journal of cardiovascular computed tomography. 2020;(4):330-334
Abstract
BACKGROUND When patients with Fontan circulation require a computed tomographic pulmonary angiogram (CTPA), there are significant challenges in achieving adequate contrast opacification due to the altered anatomical connections. This study used Time Resolved Angiography with Interleaved Stochastic Trajectories (TWIST) Magnetic Resonance Angiography (MRA) to examine contrast circulation in a cohort of patients with Fontan circulation who were having routine MRI follow up to inform the contrast timing of any subsequent CT. METHODS This is a single centre, cross-sectional, observational, retrospective study. The time to peak (TTP) signal intensity from the MRA was recorded using regions of interest on the aorta, pulmonary arteries, cavae and Fontan conduit. Patients were grouped by ejection fraction, global longitudinal strain, indexed stroke volume and cardiac index to examine if these cardiac performance parameters affected the mean TTP. Statistical analysis was performed to find the mean TTP for each of the vessels, which was consequently compared between the different cardiac performance parameters. RESULTS 35 patients were included in the study. Mean TTP contrast enhancement was 31s in the thoracic aorta, 46s in the right pulmonary artery, 41s in the left pulmonary artery and 55s in the Fontan conduit. Cardiac performance shows no statistically significant relationship to the peak contrast enhancement whether measured by ejection fraction, global longitudinal strain, stroke volume index or cardiac index. CONCLUSION The mean optimal timing for a single-phase examination of the Fontan circulation, following an upper limb injection, was 55 s following start of contrast injection irrespective of cardiac performance. In TWIST MRA, the IV bolus is 4-5 s duration. A longer bolus is required for CTA, around 20s, suggesting an additional delay will be required. We propose that an optimal single phase CTPA to be protocolled at 70 s following the start of contrast injection, assuming adequate iodinated contrast dose.
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Contrast medium injection protocols for coronary CT angiography: should contrast medium volumes be tailored to body weight or body surface area?
Yin, WH, Yu, YT, Zhang, Y, An, YQ, Hou, ZH, Gao, Y, Wang, HP, Lu, B, De Santis, D, Rollins, JD, et al
Clinical radiology. 2020;(5):395.e17-395.e24
Abstract
AIM: To compare the uniformity and image quality between contrast media injection protocols adjusted for patient body weight (BW) versus body surface area (BSA) during coronary computed tomography (CT) angiography (CCTA). MATERIALS AND METHODS Consecutive patients (n=489) with suspected coronary artery disease were randomised prospectively to one of two CCTA protocols. In the BW protocol (n=245), patients received individualised iodine delivery rates (≤50 kg: 1 g/s; 51-60 kg: 1.2 g/s; 61-70 kg: 1.4 g/s; 71-80 kg: 1.6 g/s; 81-90 kg: 1.8 g/s; 91-100 kg: 2 g/s; >100 kg: 2.2 g/s). In the BSA protocol (n=244), patients received 9,600 mg iodine/m2 of contrast medium over 12 seconds. Attenuation and image noise were measured. Signal-to-noise ratio and contrast-to-noise ratio were calculated. Image quality was scored. Attenuation was assessed for correlation with BW and BSA using linear regression. RESULTS There were no statistically significant differences in mean arterial attenuation (396.8±47.6 versus 395.8±42.2 HU, p=0.804; 95% confidence interval: -7 to 9), image noise (25.2±5.8 versus 25.5±5.4 HU; p=0.549), signal-to-noise ratio (16.7±4.4 versus 16.6±3.6; p=0.902), contrast-to-noise ratio (25.1±5.8 versus 25.8±7.4; p=0.258) or image quality scores (4.1±0.9 versus 4±0.9; p=0.770) between the BW and BSA protocols. There was no correlation between BW and aortic attenuation or between BSA and aortic attenuation (p=0.324 and 0.932, respectively). CONCLUSION The average contrast media attenuation and image quality was comparable between BW-adjusted protocol and BSA-adjusted protocol.
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Does Iodinated Contrast Affect Residual Renal Function in Dialysis Patients? A Systematic Review and Meta-Analysis.
Oloko, A, Talreja, H, Davis, A, McCormick, B, Clark, E, Akbari, A, Kong, J, Hiremath, S
Nephron. 2020;(4):176-184
Abstract
BACKGROUND It is important for medical practitioners to be aware of the effect of iodinated contrast media on the residual renal function (RRF) of dialysis patients who require diagnostic or therapeutic imaging procedures. Preservation of RRF is important given that it is a robust predictor of higher survival. However, the absence of any effect would allow for easier diagnostic or therapeutic imaging tests to be performed. OBJECTIVE This systematic review with meta-analysis will quantify the effect of intravascular administration of iodinated contrast on the residual function of adult dialysis patients. STUDY DESIGN The selection criteria included adult (age ≥ 18 years) populations undergoing dialysis, who have been administered an intravascular contrast. The primary outcome was the measurement of residual function. Secondary outcomes were disease progression from peritoneal dialysis to hemodialysis, hospitalization following contrast administration, and all-cause mortality. RESULTS Nine studies including 434 patients met the inclusion criteria. A meta-analysis was performed on 7 trials with complete quantitative data. The weighted difference in means was -0.16 mL/min (95% confidence interval -0.66 to 0.34 mL/min; p = 0.53), suggesting a small reduction in residual function following contrast administration. Significant heterogeneity in the data was observed, with a Cochran Q of 35.83 and an I2 of 83.25 (p < 0.0001). Subgroup analysis of retrospective versus prospective study design resolved heterogeneity. Few data were reported for clinical outcomes. LIMITATIONS Small sample size of included studies. CONCLUSION Intravascularly administered contrast media may not result in a significant reduction of residual function in dialysis patients.
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Effect of No Prehydration vs Sodium Bicarbonate Prehydration Prior to Contrast-Enhanced Computed Tomography in the Prevention of Postcontrast Acute Kidney Injury in Adults With Chronic Kidney Disease: The Kompas Randomized Clinical Trial.
Timal, RJ, Kooiman, J, Sijpkens, YWJ, de Vries, JPM, Verberk-Jonkers, IJAM, Brulez, HFH, van Buren, M, van der Molen, AJ, Cannegieter, SC, Putter, H, et al
JAMA internal medicine. 2020;(4):533-541
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IMPORTANCE Prevention of postcontrast acute kidney injury in patients with stage 3 chronic kidney disease (CKD) by means of prehydration has been standard care for years. However, evidence for the need for prehydration in this group is limited. OBJECTIVE To assess the renal safety of omitting prophylactic prehydration prior to iodine-based contrast media administration in patients with stage 3 CKD. DESIGN, SETTING, AND PARTICIPANTS The Kompas trial was a multicenter, noninferiority, randomized clinical trial conducted at 6 hospitals in the Netherlands in which 523 patients with stage 3 CKD were randomized in a 1:1 ratio to receive no prehydration or prehydration with 250 mL of 1.4% sodium bicarbonate administered in a 1-hour infusion before undergoing elective contrast-enhanced computed tomography from April 2013 through September 2016. Final follow-up was completed in September 2017. Data were analyzed from January 2018 to June 2019. INTERVENTIONS In total, 262 patients were allocated to the no prehydration group and 261 were allocated to receive prehydration. Analysis on the primary end point was available in 505 patients (96.6%). MAIN OUTCOMES AND MEASURES The primary end point was the mean relative increase in serum creatinine level 2 to 5 days after contrast administration compared with baseline (noninferiority margin of less than 10% increase in serum creatinine level). Secondary outcomes included the incidence of postcontrast acute kidney injury 2 to 5 days after contrast administration, mean relative increase in creatinine level 7 to 14 days after contrast administration, incidences of acute heart failure and renal failure requiring dialysis, and health care costs. RESULTS Of 554 patients randomized, 523 were included in the intention-to-treat analysis. The median (interquartile range) age was 74 (67-79) years; 336 (64.2%) were men and 187 (35.8%) were women. The mean (SD) relative increase in creatinine level 2 to 5 days after contrast administration compared with baseline was 3.0% (10.5) in the no prehydration group vs 3.5% (10.3) in the prehydration group (mean difference, 0.5; 95% CI, -1.3 to 2.3; P < .001 for noninferiority). Postcontrast acute kidney injury occurred in 11 patients (2.1%), including 7 of 262 (2.7%) in the no prehydration group and 4 of 261 (1.5%) in the prehydration group, which resulted in a relative risk of 1.7 (95% CI, 0.5-5.9; P = .36). None of the patients required dialysis or developed acute heart failure. Subgroup analyses showed no evidence of statistical interactions between treatment arms and predefined subgroups. Mean hydration costs were €119 (US $143.94) per patient in the prehydration group compared with €0 (US $0) in the no prehydration group (P < .001). Other health care costs were similar. CONCLUSIONS AND RELEVANCE Among patients with stage 3 CKD undergoing contrast-enhanced computed tomography, withholding prehydration did not compromise patient safety. The findings of this study support the option of not giving prehydration as a safe and cost-efficient measure. TRIAL REGISTRATION Netherlands Trial Register Identifier: NTR3764.
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Risk for Nephrogenic Systemic Fibrosis After Exposure to Newer Gadolinium Agents: A Systematic Review.
Lunyera, J, Mohottige, D, Alexopoulos, AS, Campbell, H, Cameron, CB, Sagalla, N, Amrhein, TJ, Crowley, MJ, Dietch, JR, Gordon, AM, et al
Annals of internal medicine. 2020;(2):110-119
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BACKGROUND The risk for nephrogenic systemic fibrosis (NSF) after exposure to newer versus older gadolinium-based contrast agents (GBCAs) remains unclear. PURPOSE To synthesize evidence about NSF risk with newer versus older GBCAs across the spectrum of kidney function. DATA SOURCES MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science for English-language references from inception to 5 March 2020. STUDY SELECTION Randomized controlled trials, cohort studies, and case-control studies that assessed NSF occurrence after GBCA exposure. DATA EXTRACTION Data were abstracted by 1 investigator and verified by a second. Investigator pairs assessed risk of bias by using validated tools. DATA SYNTHESIS Of 32 included studies, 20 allowed for assessment of NSF risk after exposure to newer GBCAs and 12 (11 cohort studies and 1 case-control study) allowed for comparison of NSF risk between newer and older GBCAs. Among 83 291 patients exposed to newer GBCAs, no NSF cases developed (exact 95% CI, 0.0001 to 0.0258 case). Among the 12 studies (n = 118 844) that allowed risk comparison between newer and older GBCAs, 37 NSF cases developed after exposure to older GBCAs (exact CI, 0.0001 to 0.0523 case) and 4 occurred (3 confounded) after exposure to newer GBCAs (exact CI, 0.0018 to 0.0204 case). Data were scant for patients with acute kidney injury or those at risk for chronic kidney disease. LIMITATIONS Study heterogeneity prevented meta-analysis. Risk of bias was high in most studies because of inadequate exposure and outcome ascertainment. CONCLUSION Although NSF occurrence after exposure to newer GBCAs is very rare, the relatively scarce data among patients with acute kidney injury and those with risk factors for chronic kidney disease limit conclusions about safety in these populations. PRIMARY FUNDING SOURCE U.S. Department of Veterans Affairs. (PROSPERO CRD42019135783).