Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum c...Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.展开更多
While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from t...While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.展开更多
基金supported by the Natural Science Foundation of Hunan Province(2023JJ60087)the Clinical Medical Technology Innovation Guidance Project of Hunan Province(2021SK53501),China。
文摘Objective:Augmented renal clearance(ARC),in contrast to renal dysfunction,refers to enhanced renal elimination of circulating solutes compared to the expected baseline.Although patients may present with normal serum creatinine(Scr)levels,the incidence of ARC is high in intensive care unit(ICU)settings.ARC is associated with subtherapeutic exposure and treatment failure of renally cleared antibiotics.However,limited research exists on the incidence and risk factors of ARC in the ICU,and even fewer data are available specifically for neurological ICU(NICU).This study aims to determine the incidence and risk factors of ARC in neurocritically ill patients.Methods:We retrospectively analyzed all available Scr data of neurocritical care patients admitted to the NICU of the Second Xiangya Hospital of Central South University between December 2020 and January 2023.Creatinine clearance(CrCl)was calculated using the Cockcroft-Gault equation.ARC was defined as a CrCl≥130 mL/(min·1.73 m^(2))sustained for more than 50%of the duration of the NICU stay.A total of 208 neurocritically ill patients were assigned into an ARC group(n=52)and a non-ARC(N-ARC)group(n=156).Clinical characteristics were compared between the 2 groups.Variables with P<0.05 in univariate analysis were included in binary Logistic regression to identify independent risk factors for ARC.Results:The incidence of ARC among neurocritically ill patients was 25.00%.Of the 74 patients with normal CrCl,20(27.03%)gradually developed ARC during hospitalization.Compared with the N-ARC group,the patients of the ARC group were younger(P<0.001),with a higher proportion of females(P=0.048)and a lower admission mean arterial pressure(MAP)(P=0.034).Moreover,patients of the ARC group were commonly complicated with severe bacterial infections compared with the patients of the N-ARC group(P<0.001).In binary Logistic regression analysis,younger age(OR=0.903,95%CI 0.872 to 0.935)and severe bacterial infections(OR=6.270,95%CI 2.568 to 15.310)were significant predictors of ARC.Conclusion:ARC is relatively common in the NICU.A considerable number of patients with initially normal renal function developed ARC during hospitalization.Younger age and concurrent severe bacterial infection are important risk factors of ARC in neurocritically ill patients.
文摘While we studied pharmacokinetics of SM-12502 which was under development as an anti-PAF agent, we found three subjects showing a slow metabolic phenotype in its pharmacokinetics. Analyzing the genes for CYP2A6 from the three subjects, we discovered that the three subjects possessed the whole CYP2A6 gene deletion (CYP2A6*4C), a novel genetic polymorphism of the CYP2A6 gene. Genetically engineered Salmonella YG7108 cells expressing human CYP2A6 or CYP2E1 together with the NADPH-CYP reductase were established in our laboratory to compare the mutagen-producing capacity of these enzymes for various N-nitrosamines. We found that CYP2E1 was responsible for the metabolic activation of N-nitrosamines with relatively short alkyl chains, whereas CYP2A6 was involved in the metabolic activation of N-nitrosamines possessing relatively bulky alkyl chains such as a tobacco-specific nitrosamine, NNK, which has been known to cause lung tumor in rodents. Thus, to examine a hypothesis that individuals possessing the CYP2A6*4C have the reduced risk of lung cancer due to the lack of the capacity of the metabolic activation of certain carcinogens in tobacco smoke, a case-control study was performed.
