Analysis Of Risk Factors Of CI-AKI And Determination Of Iodoxanol Concentration In Patients With CKD

Background: Contrast-induced acute kidney injury(CI-AKI)is a major serious adverse reaction during the use of contrast agents.Contrast agents exert renal damaging effects in a time-and concentration-dependent manner.Patients with chronic kidney disease(CKD)are at high risk of CI-AKI.Excretion of contrast agents is slowed in CKD patients,leading to prolonged renal exposure to contrast agents and increased risk of CI-AKI.At present,a large number of studies have investigated the risk factors associated with the occurrence of CI-AKI after coronary angiography(CAG)/percutaneous coronary intervention(PCI)in CKD patients,but the results of each study are still inconsistent.Objective: 1)Meta-analysis was used to analyze the risk factors associated with CI-AKI after CAG/PCI in CKD patients;2)Based on real-world data analysis of risk factors associated with AKI after CAG/PCI in Chinese CKD patients,a nomogram model to assess their risk was established;3)To establish a simple,stable and rapid high performance liquid chromatography(HPLC)method for the determination of iodixanol concentrations in human plasma and urine.Methods: 1)Pub Med,Embase,The Cochrane Library,CNKI,VIP,Wan Fang Data and Sino Med databases were electronically searched to collect relevant articles published until December 19,2021.Meta-analysis was performed by using Stata SE 15 statistical software;2)Based on real-world data analysis of risk factors associated with AKI after CAG/PCI in Chinese CKD patients,a total of 644 CKD patients were included.The endpoint was the incidence of post-contrast acute kidney injury(PC-AKI),defined as serum creatinine elevation more than26.5 μmol/L or more than 1.5 times of baseline within 72 h following contrast exposure.A nomogram model for PC-AKI risk prediction was constructed by selecting variables according to statistical significance;3)HPLC was used to determine the iodixanol concentration in human plasma and urine.The determination was performed on Waters XSelect C18 column with mobile phase consisted of acetonitrile and water at the flow rate of 1.0 m L/min(gradient elution).The column temperature was maintained at 30 ℃,and the detection wavelength was 244 nm.The sample size was 20 μL.Meanwhile,the method was applied to determine of iodixanol concentrations in plasma and urine of CKD patients.Results: 1)A total of 27 articles were included,including 19 cohort studies and 8 randomized controlled trials,and the pooled incidence of CI-AKI was 15.8%.Meta-analysis of randomized controlled trials showed that diabetes and contrast agent type were risk factors for the development of CI-AKI after CAG/PCI in CKD patients;Meta-analysis of cohort studies showed that age,female gender,basal e GFR,left fraction,diabetes,anemia,heart failure,myocardial infarction,intra-aortic balloon pump,contrast agent volume,contrast agent type and diuretics were risk factors for the development of CI-AKI after CAG/PCI in CKD patients 2)Based on real-world data,we found that hypotension and anemia were independent risk factors for the development of PC-AKI after CAG/PCI in Chinese CKD patients.We established a nomogram model for predicting the risk of PC-AKI after CAG/PCI in CKD patients,which had good predictive power,with an area under the ROC curve of0.743.The calibration curve showed that the correlation between the predicted results and the actual results was good(P=0.948);3)The linear ranges of concentration of iodixanol in plasma and urine were 10~500μg/m L(R2=0.9996)and 100~5000 μg/m L(R2=0.9997),respectively.The selectivity,lower limit of quantification,accuracy,precision and stability of the method met the criteria in Chinese Pharmacopoeia.Conclusions: 1)Meta-analysis showed that age,female gender,basal e GFR,ejection fraction,diabetes,anemia,heart failure,myocardial infarction,intra-aortic balloon pump,contrast medium volume,contrast medium type and diuretics were risk factors for CI-AKI after CAG/PCI in CKD patients;2)Hypotension and anemia were independent risk factors for PC-AKI after CAG/PCI in Chinese CKD patients.We developed a nomogram model to predict the risk of PC-AKI after CAG/PCI in CKD patients,which has good discrimination with accuracy;3)We developed a simple,rapid,stable and validated HPLC method for the determination of iodixanol concentrations in human plasma and urine.