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CETP genetic variant rs1800777 (allele A) is associated with abnormally low HDL-C levels and increased risk of AKI during sepsis.
Genga, KR, Trinder, M, Kong, HJ, Li, X, Leung, AKK, Shimada, T, Walley, KR, Russell, JA, Francis, GA, Brunham, LR, et al
Scientific reports. 2018;(1):16764
Abstract
High-density cholesterol (HDL-C) levels are influenced by genetic variation in several genes. Low levels of HDL-C have been associated with increased risk of acute kidney injury (AKI). We investigated whether genetic polymorphisms in ten genes known to regulate HDL-C levels are associated with both HDL-C levels and AKI development during sepsis. Two cohorts were retrospectively analyzed: Derivation Cohort (202 patients with sepsis enrolled at the Emergency Department from 2011 to 2014 in Vancouver, Canada); Validation Cohort (604 septic shock patients enrolled into the Vasopressin in Septic Shock Trial (VASST)). Associations between HDL-related genetic polymorphisms and both HDL-C levels, and risk for clinically significant sepsis-associated AKI (AKI KDIGO stages 2 and 3) were evaluated. In the Derivation Cohort, one genetic variant in the Cholesteryl Ester Transfer Protein (CETP) gene, rs1800777 (allele A), was strongly associated with lower HDL-C levels (17.4 mg/dL vs. 32.9 mg/dL, P = 0.002), greater CETP mass (3.43 µg/mL vs. 1.32 µg/mL, P = 0.034), and increased risk of clinically significant sepsis-associated AKI (OR: 8.28, p = 0.013). Moreover, the same allele was a predictor of sepsis-associated AKI in the Validation Cohort (OR: 2.38, p = 0.020). Our findings suggest that CETP modulates HDL-C levels in sepsis. CETP genotype may identify patients at high-risk of sepsis-associated AKI.
2.
[Effect of the ischemic post-conditioning on the prevention of the cardio-renal damage in patients with acute ST-segment elevation myocardial infarction after primary percutaneous coronary intervention].
Wang, YY, Li, T, Liu, YW, Liu, BJ, Hu, XM, Wang, Y, Gao, WQ, Wu, P, Huang, L, Li, X, et al
Zhonghua xin xue guan bing za zhi. 2017;(4):277-282
Abstract
Objective: To evaluate the effect of the ischemic post-conditioning (IPC) on the prevention of the cardio-renal damage in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PPCI). Methods: A total of 251 consecutive STEMI patients underwent PPCI in the heart center of Tianjin Third Central Hospital from January 2012 to June 2014 were enrolled in this prospective, randomized, control, single-blinded, clinical registry study. Patients were randomly divided into IPC group (123 cases) and control group (128 cases) with random number table. Patients in IPC group underwent three times of inflation/deflation with low inflation pressure using a balloon catheter within one minute after culprit vessel blood recovery, and then treated by PPCI. Patients in control group received PPCI procedure directly. The basic clinical characteristics, incidence of reperfusion arrhythmia during the procedure, the rate of electrocardiogram ST-segment decline, peak value of myocardial necrosis markers, incidence of contrast induced acute kidney injury(CI-AKI), and one-year major adverse cardiovascular events(MACE) which including myocardial infarction again, malignant arrhythmia, rehospitalization for heart failure, repeat revascularization, stroke, and death after the procedure were analyzed between the two groups. Results: The age of IPC group and control group were comparable((61.2±12.6) vs. (64.2±12.1) years old, P=0.768). The incidence of reperfusion arrhythmia during the procedure was significantly lower in the IPC group than in the control group(42.28% (52/123) vs. 57.03% (73/128), P=0.023). The rate of electrocardiogram ST-segment decline immediately after the procedure was significantly higher in the IPC group than in the control group (77.24% (95/123) vs. 64.84% (83/128), P=0.037). The peak value of myocardial necrosis markers after the procedure were significantly lower in the IPC group than in the control group(creatine kinase: 1 257 (682, 2 202) U/L vs. 1 737(794, 2 816)U/L, P=0.029; creatine kinase-MB: 123(75, 218)U/L vs.165(95, 288)U/L, P=0.010). The rate of CI-AKI after the procedure was significantly lower in the IPC group than in the control group(5.69%(7/123) vs. 14.06%(18/128), P=0.034). The rate of the one-year MACE was significantly lower in the IPC group than in the control group(7.32%(9/123) vs. 15.63% (20/128), P=0.040). Conclusion: The IPC strategy performed eight before PPCI can reduce myocardial ischemia- reperfusion injury, decline the rates of CI-AKI and one-year MACE significantly in STEMI patients, thus has a significant protective effect on heart and kidney in STEMI patients. Clinical Trial Registration Chinese Clinical Trials Registry, ChiCTR-ICR-15006590.
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Cumulative Fluid Balance and Mortality in Septic Patients With or Without Acute Kidney Injury and Chronic Kidney Disease.
Neyra, JA, Li, X, Canepa-Escaro, F, Adams-Huet, B, Toto, RD, Yee, J, Hedayati, SS, ,
Critical care medicine. 2016;(10):1891-900
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Abstract
OBJECTIVE Incident acute kidney injury and prevalent chronic kidney disease are commonly encountered in septic patients. We examined the differential effect of acute kidney injury and chronic kidney disease on the association between cumulative fluid balance and hospital mortality in critically ill septic patients. DESIGN Retrospective cohort study. SETTING Urban academic medical center ICU. PATIENTS ICU adult patients with severe sepsis or septic shock and serum creatinine measured within 3 months prior to and 72 hours of ICU admission. Patients with estimated glomerular filtration rate less than 15 mL/min/1.73 m or receiving chronic dialysis were excluded. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS A total of 2,632 patients, 1,211 with chronic kidney disease, were followed up until hospital death or discharge. Acute kidney injury occurred in 1,525 patients (57.9%), of whom 679 (44.5%) had chronic kidney disease. Hospital mortality occurred in 603 patients (22.9%). Every 1-L increase in cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality in all patients (adjusted odds ratio, 1.06 [95% CI] 1.04-1.08; p < 0.001), and in each acute kidney injury/chronic kidney disease subgroup (adjusted odds ratio, 1.06 [1.03-1.09] for acute kidney injury+/chronic kidney disease+; 1.09 [1.05-1.13] for acute kidney injury-/chronic kidney disease+; 1.05 [1.03-1.08] for acute kidney injury+/chronic kidney disease-; and 1.07 [1.02-1.11] for acute kidney injury-/chronic kidney disease-). There was a significant interaction between acute kidney injury and chronic kidney disease on cumulative fluid balance (p =0.005) such that different cumulative fluid balance cut-offs with the best prognostic accuracy for hospital mortality were identified: 5.9 L for acute kidney injury+/chronic kidney disease+; 3.8 L for acute kidney injury-/chronic kidney disease+; 4.3 L for acute kidney injury+/chronic kidney disease-; and 1.5 L for acute kidney injury-/chronic kidney disease-. The addition of cumulative fluid balance to the admission Sequential Organ Failure Assessment score had increased prognostic utility for hospital mortality when compared with Sequential Organ Failure Assessment alone, particularly in patients with acute kidney injury. CONCLUSIONS Higher cumulative fluid balance at 72 hours of ICU admission was independently associated with hospital mortality regardless of acute kidney injury or chronic kidney disease presence. We characterized cumulative fluid balance cut-offs associated with hospital mortality based on acute kidney injury/chronic kidney disease status, underpinning the heterogeneity of fluid regulation in sepsis and kidney disease.