Kidney function

肾功能
  • 文章类型: Journal Article
    与其他地区相比,台湾的透析发病率和患病率较高。因此,在台湾,减轻慢性肾脏病(CKD)和肾功能恶化已成为重要的医疗优先事项.已知热应激是CKD和肾功能损害的重要危险因素。然而,男性和女性之间热应激影响的差异仍未被探索。我们使用台湾生物库(TWB)的数据进行了回顾性横断面分析,根据参与者的住址,纳入中午(上午11点至下午2点)和工作时间(上午8点至下午5点)期间的湿球温度(WBGT)记录。平均1-,3-,并使用基于地理空间人工智能的集成混合空间模型计算和分析了调查年之前的5年WBGT值,涵盖2010年至2020年期间。共有114,483名来自TWB的参与者参加了这项研究。其中35.9%为男性,1053例肾功能受损(定义为估计肾小球滤过率<60ml/min/1.73m2)。多变量分析表明,在男性参与者中,在中午期间,1-,3-,和5年平均每增加1℃的WBGT值与eGFR<60ml/min/1.73m2(比值比[OR],1.096,95%置信区间[CI]=1.002-1.199,1年p=0.044;OR,1.093,95%CI=1.000-1.196,3年p=0.005;OR,1.094,95%CI=1.002-1.195,5年p=0.045)。然而,在工作时间期间没有发现显著的关联.在女性参与者中,在中午期间,1-,3-,5年平均WBGT值每增加1℃与eGFR<60ml/min/1.73m2(OR,0.872,95%CI=0.778-0.976,1年p=0.018;OR,0.874,95%CI=0.780-0.978,3年p=0.019;OR,0.875,95%CI=0.784-0.977,5年p=0.018)。此外,在工作时间期间,1-,3-,5年平均WBGT值每增加1℃也与eGFR<60ml/min/1.73m2(OR,0.856,95%CI=0.774-0.946,1年p=0.002;OR,0.856,95%CI=0.774-0.948,3年p=0.003;OR,0.853,95%CI=0.772-0.943,5年p=0.002)。总之,我们的结果显示,男性WBGT增加与肾功能受损有关,而增加的WBGT与女性肾功能受损的保护作用相关。需要进一步的研究来阐明这些性别特异性差异的确切机制。
    The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants\' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 ℃ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.
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  • 文章类型: Journal Article
    处方者通常面临预测65岁或以上且血清肌酐(SCr)浓度低于1mg/dL的老年患者的肌酐清除率(CrCl)的挑战。研究表明,利用圆形SCr会低估该人群中的CrCl,这可能导致万古霉素等药物的剂量不足。目前的研究旨在比较老年患者使用实际SCr与圆形SCr至1mg/dL的万古霉素给药的准确性。共纳入245例患者。使用实际SCr的138例(56.3%)患者达到了治疗谷水平(10-20mg/L)。在32(13.1%)和75(30.6%)患者中观察到亚治疗(<10mg/L)和超治疗(>20mg/L)谷水平,分别。与目标维持剂量(TMD)相比,基于实际SCr和圆形SCr的不同万古霉素剂量的预测性能显示,基于实际SCr的剂量与TMD的剂量具有更强的相关性(r=0.55vs.0.31)与舍入的SCr剂量相比;两种剂量显示相似的精确度,基于实际SCr的剂量范围为±552mg/天,基于四舍五入的SCr的剂量范围为±691mg/天。此外,与基于舍入SCr的剂量相比,基于实际SCr的剂量在TMD的±10%内显示出较低的误差百分比(69%)和较高的准确率(57.6%)。误差百分比为(92.3%),准确率为(40%)。万古霉素相关肾毒性(VAN)的患病率在44例(18%)患者中可见。75至84岁的患者,那些卧床不起的人,万古霉素谷浓度大于20mg/L的患者发生VAN的风险较高。总之,在老年患者中,与四舍五入的SCr至1mg/dL相比,根据实际SCr估算万古霉素给药更准确.万古霉素的疗效可能会受到SCr四舍五入的负面影响,这可能会低估CrCl并导致万古霉素的剂量不足。
    Prescribers often face the challenge of predicting creatinine clearance (CrCl) in elderly patients who are 65 years or older and have serum creatinine (SCr) concentrations below 1 mg/dL. Studies have shown that utilizing rounded SCr would underestimate CrCl in this population, which could lead to the under-dosing of some medications like vancomycin. The current study aimed to compare the accuracy of vancomycin dosing using actual SCr versus rounded SCr to 1 mg/dL in elderly patients. A total of 245 patients were included. The therapeutic trough level (10-20 mg/L) was achieved in 138 (56.3%) patients using actual SCr. Sub-therapeutic (<10 mg/L) and supra-therapeutic (>20 mg/L) trough levels were observed in 32 (13.1%) and 75 (30.6%) patients, respectively. The predictive performance of different vancomycin doses based on actual SCr and rounded SCr compared to the targeted maintenance dose (TMD) showed a stronger correlation of dosing based on actual SCr with TMD (r = 0.55 vs. 0.31) compared to rounded SCr dosing; both doses showed similar precision, with ranges of ±552 mg/day for the dosing based on actual SCr and ±691 mg/day for the dosing based on rounded SCr. Furthermore, the dosing based on actual SCr showed a lower error percentage (69%) and a higher accuracy rate (57.6%) within ±10% of the TMD compared to the dosing based on rounded SCr, which had an error percentage of (92.3%) and an accuracy rate of (40%). The prevalence of vancomycin-associated nephrotoxicity (VAN) was seen in 44 (18%) patients. Patients between 75 and 84 years of age, those who were bedridden, and those with vancomycin trough concentrations greater than 20 mg/L had a higher risk of developing VAN. In conclusion, in elderly patients, estimating vancomycin dosing based on actual SCr was more accurate compared to rounded SCr to 1 mg/dL. The efficacy of vancomycin could be negatively affected by rounding up SCr, which could underestimate CrCl and result in the under-dosing of vancomycin.
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  • 文章类型: Journal Article
    背景:一些研究报道普伐他汀可以缓解肾脏疾病的进展,但是关于其对亚洲患者肾功能的影响的证据有限。这项多中心前瞻性观察性研究旨在评估普伐他汀对韩国血脂异常和2型糖尿病(T2DM)患者在临床实践中的肾功能的影响。
    方法:这项为期48周的前瞻性多中心研究纳入了2997名符合血脂异常和T2DM患者中的2604名,这些患者具有估计的肾小球滤过率(eGFR)测量值。主要终点是第24周的eGFR相对于基线的变化百分比。我们还评估了次要终点,其中包括12周和48周时eGFR相对于基线的百分比变化,以及eGFR的变化,从基线开始12、24和48周的代谢谱(脂质和血糖水平),和安全。
    结果:我们注意到eGFR的显着改善,平均百分比变化为2.5%,2.5%,在12、24和48周时为3.0%,分别(所有调整后的p<0.05)。基线eGFR30-90mL/min/1.73m2,基线糖化血红蛋白(HbA1c)≥7的亚组eGFR百分比变化显着增加,无高血压史,T2DM病程>5年,或以前的他汀类药物治疗。在整个研究过程中,脂质分布得到改善并保持稳定。有趣的是,24周时空腹血糖和HbA1c改善.
    结论:我们的研究结果表明,普伐他汀可能对改善韩国血脂异常和T2DM患者的eGFR有潜在益处。这可以使其成为肾功能降低的患者的优选治疗选择。
    背景:NCT05107063于2021年10月27日提交。
    BACKGROUND: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice.
    METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety.
    RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks.
    CONCLUSIONS: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function.
    BACKGROUND: NCT05107063 submitted October 27, 2021.
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  • 文章类型: Journal Article
    这项横断面研究的目的是阐明身体活动的各个领域之间的关联,例如与职业相关的(OPA),交通相关(TPA),休闲时间(LTPA)和整体体力活动(PA),和糖尿病肾病。
    我们的研究包括2,633名参与者,从2007年至2018年国家健康和营养调查(NHANES)的横断面调查中得出,并采用调查加权逻辑回归,广义线性回归,和限制性三次样条(RCS)分析,以确定不同领域的体力活动与糖尿病肾病之间的关系。
    控制所有混杂因素后,多变量逻辑回归分析显示,身体活动的各个领域与糖尿病肾病的患病率之间缺乏相关性。多元广义线性回归分析显示,PA(β=0.05,95%CI,0.01-0.09,P=0.012)和TPA(β=0.32,95%CI,0.10-0.55,P=0.006)的持续时间与eGFR水平呈正相关;LTPA持续时间与UACR水平呈负相关(β=-5.97,95%CI,-10.50-1.44,P=0.011)。RCS曲线表明PA,OPA,和eGFR,以及PA和ACR之间的非线性相关性。亚组和敏感性分析在很大程度上与多元广义线性回归的结果一致,强调了我们研究结果的稳健性。
    我们基于人群的研究探讨了不同领域的体力活动与糖尿病肾病之间的关联。与我们的期望相反,我们发现所有领域的体力活动持续时间与糖尿病肾病的患病率之间没有显著关联.尽管如此,肾功能标志物,包括eGFR和UACR,与总体力活动(TPA)和休闲时间体力活动(LTPA)的持续时间显着相关,分别,在糖尿病患者中。有趣的是,我们的研究结果表明,糖尿病患者进行体育锻炼以保护肾功能,确保每周不超过35小时的适度运动持续时间。
    UNASSIGNED: The aim of this cross-sectional study was to elucidate the associations between various domains of physical activity, such as occupation-related (OPA), transportation-related (TPA), leisure-time (LTPA) and overall physical activity (PA), and diabetic kidney disease.
    UNASSIGNED: Our study encompassed 2,633 participants, drawn from the cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, and employed survey-weighted logistic regression, generalized linear regression, and restricted cubic spline (RCS) analyses to ascertain the relationship between different domains of physical activity and diabetic kidney disease.
    UNASSIGNED: After controlling for all confounders, multivariate logistic regression analyses revealed a lack of correlation between the various domains of physical activity and the prevalence of diabetic kidney disease. Multiple generalized linear regression analyses showed that durations of PA (β = 0.05, 95% CI, 0.01-0.09, P = 0.012) and TPA (β = 0.32, 95% CI, 0.10-0.55, P = 0.006) were positively associated with eGFR levels; and LTPA durations were inversely associated with UACR levels (β = -5.97, 95% CI, -10.50 - -1.44, P = 0.011). The RCS curves demonstrated a nonlinear relationship between PA, OPA, and eGFR, as well as a nonlinear correlation between PA and ACR. Subgroup and sensitivity analyses largely aligned with the outcomes of the multivariate generalized linear regression, underscoring the robustness of our findings.
    UNASSIGNED: Our population-based study explored the association between different domains of physical activity and diabetic kidney disease. Contrary to our expectations, we found no significant association between the duration of physical activity across all domains and the prevalence of diabetic nephropathy. Nonetheless, renal function markers, including eGFR and UACR, exhibited significant correlations with the duration of total physical activity (TPA) and leisure-time physical activity (LTPA), respectively, among diabetic patients. Interestingly, our findings suggest that diabetic patients engage in physical activity to preserve renal function, ensuring moderate exercise durations not exceeding 35 hours per week.
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  • 文章类型: Journal Article
    在肾功能良好的中年人中,载脂蛋白L1(APOL1)基因型对未来肾病风险的影响尚不明确。
    纵向队列研究。
    总共,5,886名健康个体(45-64岁)参加了社区动脉粥样硬化风险研究,其基于肌酐的估计肾小球滤过率≥80mL/min,将是合适的肾脏供体。
    种族和APOL1基因型。
    使用CKD-EPI(慢性肾脏病流行病学合作)2021方程,基于肌动蛋白和胱抑素C的估计肾小球滤过率(eGFRcr-cys),尿白蛋白-肌酐比值(UACR),慢性肾脏病(CKD)3a或更严重的比例,终末期肾病(ESKD),和死亡。
    参与者根据种族和APOL1基因型进行分组。各组比较eGFRcr-cys和UACR。使用多项逻辑回归模型比较CKD的几率。建立Kaplan-Meier存活曲线以比较最后随访时的ESKD和死亡率。
    有5,075名白人(86%),701携带低风险APOL1基因型的黑人(12%),和110名携带高风险APOL1基因型的黑人(2%)。基线时的平均年龄为53±6岁。十年后,白人参与者的eGFRcr-cys低于低危和高危人群(分别为89±16vs91±16和92±15mL/min/1.73m2;P<0.001)。25岁时,白人参与者的eGFRcr-cys继续低于低风险组(70±18vs72±19mL/min/1.73m2;P<0.001),但与高风险APOL1基因型(67±23mL/min/1.73m2)相比没有。在10岁和25岁时,各组之间的UACR没有差异(分别为P=0.87和0.91)。在未调整模型和调整模型中,低风险和高风险APOL1组发生CKD3a期或更差的几率没有差异(分别为P=0.26和P=0.39)。在最后的随访中,<5%发达的ESKD,45%的个体死亡或达到ESKD,组间结局无差异.
    由于死亡和长期随访而导致的确定性低。
    在中年人中,APOL1基因型似乎不是未来肾病风险的主要驱动因素。
    患有肾病的黑人患者携带2种载脂蛋白L1(APOL1)基因变体,被称为高风险基因型,与具有0或1个风险变异的患者相比,肾功能加速下降。尚不清楚高危基因型是否会对健康中年人的肾功能产生负面影响。我们评估了APOL1基因型对基线时肾功能和血压正常的社区动脉粥样硬化风险研究参与者(平均年龄53岁)的肾功能的影响。在25年的随访中,APOL1高危基因型似乎不是未来肾病风险的主要驱动因素.我们的研究结果与老年活体捐献者以及APOL1相关肾脏疾病患者的家庭成员的咨询有关。
    UNASSIGNED: The effect of apolipoprotein L1(APOL1) genotype on future risk of kidney disease among middle-aged individuals with good kidney function is not well established.
    UNASSIGNED: Longitudinal cohort study.
    UNASSIGNED: In total, 5,886 healthy individuals (45-64 years old) enrolled in the Atherosclerosis Risk in Communities study with creatinine-based estimated glomerular filtration rate ≥ 80 mL/min who would be suitable kidney donors.
    UNASSIGNED: Race and APOL1 genotype.
    UNASSIGNED: Creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) 2021 equation, urinary albumin-creatinine ratio (UACR), proportion with chronic kidney disease (CKD) 3a or worse, end-stage kidney disease (ESKD), and death.
    UNASSIGNED: Participants grouped based on race and APOL1 genotype. Compared eGFRcr-cys and UACR across groups. Multinomial logistic regression models were used compare odds of CKD. Kaplan-Meier survival curves were created to compare rates of ESKD and death at last follow-up.
    UNASSIGNED: There were 5,075 Whites (86%), 701 Blacks carrying the low-risk APOL1 genotype (12%), and 110 Blacks carrying the high-risk APOL1 genotype (2%). The mean age at baseline was 53 ± 6 years. At 10 years, White participants had lower eGFRcr-cys than low-risk and high-risk groups (89 ± 16 vs 91 ± 16 and 92 ± 15 mL/min/1.73 m2, respectively; P < 0.001). At 25 years, White participants continued to have lower eGFRcr-cys than the low-risk group (70 ± 18 vs 72 ± 19 mL/min/1.73 m2; P < 0.001) but not compared with the high-risk APOL1 genotype (67±23 mL/min/1.73 m2). There was no difference in UACR among groups at 10 and 25 years (P = 0.87 and 0.91, respectively). The odds of developing CKD stage 3a or worse were not different between low-risk and high-risk APOL1 group in both unadjusted and adjusted models (P = 0.26 and P = 0.39, respectively). At last follow-up, <5% developed ESKD, and 45% of individuals either died or reached ESKD with no difference in outcomes between the groups.
    UNASSIGNED: Low ascertainment because of death and long follow-up.
    UNASSIGNED: Among middle-aged individuals, APOL1 genotype does not appear to be a major driver of future risk of kidney disease.
    Black patients with kidney disease carrying 2 variants of the apolipoprotein L1 (APOL1) gene, referred to as the high-risk genotype, experience an accelerated decline in kidney function than those with 0 or 1 risk variant. It is unknown whether the high-risk genotype negatively affects kidney function of healthy middle-aged individuals. We evaluated the effect of APOL1 genotype on kidney function of the Atherosclerosis Risk in Communities study participants (mean age 53 years) who had normal kidney function and blood pressure at baseline. At 25 years of follow-up, the APOL1 high-risk genotype did not appear to be a major driver of future risk of kidney disease. Our study findings are relevant for counseling older living donor candidates as well as family members of patients with APOL1-associated kidney disease.
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  • 文章类型: Journal Article
    肥胖是众所周知的慢性肾病及其进展的危险因素。然而,肥胖对老年人肾功能的影响尚不确定.我们调查了老年人肥胖与肾脏结局之间的关系。
    我们分析了来自韩国国民健康保险服务高级队列的130,504名参与者。肥胖根据体重指数(BMI)进行分类,性别特异性腰围(WC),和代谢综合征的存在。主要结果是肾功能下降,定义为估计的肾小球滤过率(eGFR)从基线或新发终末期肾病下降至少50%.
    在559,531.1人年的随访期间(中位数,4.3years),2,486名参与者(19.0%;发生率为4.44/1000人年)表现出肾功能下降。多变量Cox比例风险模型显示BMI/WC与肾功能下降无关。然而,与无代谢综合征组相比,有代谢综合征组肾功能下降的风险显著增加(调整后的风险比[HR],1.24;95%置信区间[CI],1.13-1.36)。与非代谢综合征组相比,具有一到五个成分的参与者的调整后的HR(95%CI)为0.96(0.84-1.11),1.10(0.96-1.27),1.24(1.06-1.45),1.37(1.12-1.66),和1.99(1.42-2.79),分别(趋势p<0.001)。
    在韩国老年人中,代谢综合征及其成分的数量与肾功能下降的高风险相关,但BMI或WC不显著。
    UNASSIGNED: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly.
    UNASSIGNED: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease.
    UNASSIGNED: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001).
    UNASSIGNED: In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.
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  • 文章类型: Journal Article
    背景:先前的观察性研究报道,全身性炎症调节因子与慢性肾脏病(CKD)的发展有关;然而,这些关联是否是因果关系尚不清楚.本研究旨在探讨全身炎症调节因子与CKD和肾功能之间的潜在因果关系。
    方法:我们进行了双向双样本孟德尔随机化(MR)分析,以推断41个全身炎症调节因子与CKD和肾功能之间的潜在因果关系。采用方差逆加权(IVW)检验作为主要分析方法。此外,通过孟德尔随机化多效性残差和异常值(MR-PRESSO)检验和加权中位数检验进行敏感性分析.
    结果:研究结果显示,在正向分析中,11种遗传预测的全身性炎症调节因子与CKD或肾功能之间存在12种暗示性关联。包括4个CKD,3为血尿素氮(BUN),4用于eGFRcrea,1用于eGFRcys。在另一个方向,我们确定了6个显著的因果关系,包括粒细胞集落刺激因子(GCSF)的CKD(IVWβ=0.145;95%CI,0.042至0.248;P=0.006),CKD伴干细胞因子(SCF)(IVWβ=0.228;95%CI,0.133~0.323;P=2.40×10-6),eGFRcrea与SCF(IVWβ=-2.90;95%CI,-3.934至-1.867;P=3.76×10-8),eGFRcys与GCSF(IVWβ=-1.382;95%CI,-2.404至-0.361;P=0.008),eGFRcys与干扰素γ(IFNg)(IVWβ=-1.339;95%CI,-2.313至-0.366;P=0.007)和eGFRcys与血管内皮生长因子(VEGF)(IVWβ=-1.709;95%CI,-2.720至-0.699;P=9.13×10-4)。
    结论:我们的发现在正向和反向MR分析中都支持全身炎症调节因子与CKD或肾功能之间的因果关系。
    BACKGROUND: Previous observational studies have reported that systemic inflammatory regulators are related to the development of chronic kidney disease (CKD); however, whether these associations are causal remains unclear. The current study aimed to investigate the potential causal relationships between systemic inflammatory regulators and CKD and kidney function.
    METHODS: We performed bidirectional two-sample Mendelian randomization (MR) analyses to infer the underlying causal associations between 41 systemic inflammatory regulators and CKD and kidney function. The inverse-variance weighting (IVW) test was used as the primary analysis method. In addition, sensitivity analyses were executed via the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test and the weighted median test.
    RESULTS: The findings revealed 12 suggestive associations between 11 genetically predicted systemic inflammatory regulators and CKD or kidney function in the forward analyses, including 4 for CKD, 3 for blood urea nitrogen (BUN), 4 for eGFRcrea and 1 for eGFRcys. In the other direction, we identified 6 significant causal associations, including CKD with granulocyte-colony stimulating factor (GCSF) (IVW β = 0.145; 95% CI, 0.042 to 0.248; P = 0.006), CKD with stem cell factor (SCF) (IVW β = 0.228; 95% CI, 0.133 to 0.323; P = 2.40 × 10- 6), eGFRcrea with SCF (IVW β =-2.90; 95% CI, -3.934 to -1.867; P = 3.76 × 10- 8), eGFRcys with GCSF (IVW β =-1.382; 95% CI, -2.404 to -0.361; P = 0.008), eGFRcys with interferon gamma (IFNg) (IVW β =-1.339; 95% CI, -2.313 to -0.366; P = 0.007) and eGFRcys with vascular endothelial growth factor (VEGF) (IVW β =-1.709; 95% CI, -2.720 to -0.699; P = 9.13 × 10- 4).
    CONCLUSIONS: Our findings support causal links between systemic inflammatory regulators and CKD or kidney function both in the forward and reverse MR analyses.
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  • 文章类型: Journal Article
    基础代谢率(BMR)与慢性肾脏病(CKD)之间的关系仍不清楚且存在争议。在这项研究中,我们调查了BMR在肾损伤中的因果关系,相反,肾功能改变是否导致BMR改变。
    在这项双样本孟德尔随机化(MR)研究中,遗传数据来自已发表的BMR全基因组关联研究(GWAS)((n=454,874)和肾功能指标,即基于肌酐的估计肾小球滤过率(eGFR)(n=1,004,040),CKD(n=480,698),和血尿素氮(BUN)(n=852,678)在欧洲。逆方差加权(IVW)随机效应MR方法作为主要分析,伴随着一些敏感性MR分析。我们还进行了反向MR,以探讨上述肾功能指标对BMR的因果关系。
    我们发现遗传预测的BMR与eGFR呈负相关,(β=-0.032,P=4.95*10-12)。使用MR-Egger获得了类似的结果(β=-0.040,P=0.002),加权中位数(β=-0.04,P=5.35×10-11)和加权模式法(β=-0.05,P=9.92×10-7)。较高的BMR对CKD风险增加有因果关系(OR=1.36,95%CI=1.11-1.66,P=0.003)。在反向MR中,较低的eGFR与较高的BMR相关(β=-0.64,P=2.32×10-6,IVW分析)。双向MR支持在BMR和BUN之间没有观察到因果关系。敏感性分析证实了这些发现,表明结果的稳健性。
    遗传预测的高BMR与肾功能受损有关。相反,遗传预测的eGFR降低与较高的BMR相关。
    UNASSIGNED: The relationship between basal metabolic rate (BMR) and Chronic kidney disease (CKD) remains unclear and controversial. In this study, we investigated the causal role of BMR in renal injury, and inversely, whether altered renal function causes changes in BMR.
    UNASSIGNED: In this two-sample mendelian randomization (MR) study, Genetic data were accessed from published genome-wide association studies (GWAS) for BMR ((n = 454,874) and indices of renal function, i.e. estimated glomerular filtration rate (eGFR) based on creatinine (n =1, 004, 040), CKD (n=480, 698), and blood urea nitrogen (BUN) (n =852, 678) in European. The inverse variance weighted (IVW) random-effects MR method serves as the main analysis, accompanied by several sensitivity MR analyses. We also performed a reverse MR to explore the causal effects of the above indices of renal function on the BMR.
    UNASSIGNED: We found that genetically predicted BMR was negatively related to eGFR, (β= -0.032, P = 4.95*10-12). Similar results were obtained using the MR-Egger (β= -0.040, P = 0.002), weighted median (β= -0.04, P= 5.35×10-11) and weighted mode method (β= -0.05, P=9.92×10-7). Higher BMR had a causal effect on an increased risk of CKD (OR =1.36, 95% CI = 1.11-1.66, P =0.003). In reverse MR, lower eGFR was related to higher BMR (β= -0.64, P = 2.32×10-6, IVW analysis). Bidirectional MR supports no causal association was observed between BMR and BUN. Sensitivity analyses confirmed these findings, indicating the robustness of the results.
    UNASSIGNED: Genetically predicted high BMR is associated with impaired kidney function. Conversely, genetically predicted decreased eGFR is associated with higher BMR.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    慢性肾脏病(CKD)的发病率和死亡率在全球范围内都在增加,使其成为严重的公共卫生问题。尽管已经提出了体内含水量与CKD进展之间的潜在相关性,因果关系的存在仍然不确定.本研究旨在确定人体含水量对肾功能的因果关系。
    来自英国生物库的全基因组关联研究摘要数据用于评估与全身水质量(BWM)相关的单核苷酸多态性(SNP)。从CKDGen财团中提取了与肾功能有关的汇总统计数据。主要肾功能结果测量包括估计的肾小球滤过率(eGFR),白蛋白尿,CKD3-5期,快速进展为CKD(CKDi25)。双样本孟德尔随机化(MR)分析估计了BWM与肾功能之间的潜在因果关系。采用逆方差加权MR方法作为主要分析,伴随着一些敏感的MR分析。
    BWM的增加与eGFR的降低呈相关性(β=-0.02;P=6.95×10-16)。不包括13个负责多效性的SNP(P=0.05),BWM的升高还与尿白蛋白与肌酐比值的降低有关(β=-0.16;P=5.91×10-36)。对于BWM的每个标准偏差增加,CKD3-5期的风险增加32%(OR,1.32;95%CI,1.19-1.47;P=1.43×10-7),CKDi25的风险增加22%(OR,1.22;95%CI,1.07-1.38;P=0.002)。
    BWM的增加与肾功能受损有关。积极管理体内水分含量对预防CKD的进展具有重要意义。
    UNASSIGNED: The morbidity and mortality of chronic kidney disease (CKD) are increasing worldwide, making it a serious public health problem. Although a potential correlation between body water content and CKD progression has been suggested, the presence of a causal association remains uncertain. This study aimed to determine the causal effect of body water content on kidney function.
    UNASSIGNED: Genome-wide association study summary data sourced from UK Biobank were used to evaluate single-nucleotide polymorphisms (SNPs) associated with whole-body water mass (BWM). The summary statistics pertaining to kidney function were extracted from the CKDGen consortium. The primary kidney function outcome measures included estimated glomerular filtration rate (eGFR), albuminuria, CKD stages 3-5, and rapid progression to CKD (CKDi25). Two-sample Mendelian randomization (MR) analysis estimated a potential causal relationship between the BWM and kidney function. The inverse variance weighted MR method was used as the primary analysis, accompanied by several sensitive MR analyses.
    UNASSIGNED: The increase of BWM exhibited a correlation with a reduction in eGFR (β = -0.02; P = 6.95 × 10-16). Excluding 13 SNPs responsible for pleiotropy (P = 0.05), the increase of BWM was also associated with the decrease of the ratio of urinary albumin to creatinine (β = -0.16; P = 5.91 × 10-36). For each standard deviation increase in BWM, the risk of CKD stages 3-5 increases by 32% (OR, 1.32; 95% CI, 1.19-1.47; P = 1.43 × 10-7), and the risk of CKDi25 increases by 22% (OR, 1.22; 95% CI, 1.07-1.38; P = 0.002).
    UNASSIGNED: The increase of BWM is associated with impaired kidney function. Proactively managing body water content is of great significance in preventing the progression of CKD.
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