Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer.
Medication-Related Adverse Events and Discordancies in Cystatin C-Based vs Serum Creatinine-Based Estimated Glomerular Filtration Rate in Patients With Cancer.
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DOI：
10.1001/jamanetworkopen.2023.21715
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发表时间：
2023-07-03
影响因子：
13.8
通讯作者：
Sise, Meghan E.
中科院分区：
文献类型：
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作者：
Hanna, Paul E.;Wang, Qiyu;Strohbehn, Ian A.;Moreno, Daiana;Harden, Destiny;Ouyang, Tianqi;Katz-Agranov, Nurit;Seethapathy, Harish;Reynolds, Kerry L.;Gupta, Shruti;Leaf, David E.;Sise, Meghan E.
这项队列研究评估了成人癌症患者超治疗剂量、高钾血症、毒性反应和死亡率的风险，这些患者的血清肌酐水平低于基于胱抑素C的估计肾小球滤过率。在癌症患者中，基于肌酐的估计肾小球滤过率(EGFRcr)和基于胱抑素C的EGFR(EGFRcys)的不一致的后果是什么？在这项对1869名成年癌症患者进行的队列研究中，eGFRcys低于其eGFRcr超过30%的患者发生超治疗万古霉素水平、与甲氧苄氨嘧啶-磺胺甲恶唑相关的高钾血症、巴氯芬中毒效应、高地高辛水平以及30天内死亡风险增加。这项研究的结果表明，与药物相关的不良事件更多发生在eGFRcys比eGFRcr低30%以上的患者中，这使得未来的研究有必要改进和个性化癌症患者的肾小球滤过率估计和用药剂量。在癌症患者中，基于肌酐的估计肾小球滤过率(EGFRcr)可能高估了肾小球滤过率(GFR)。以胱抑素C为基础的EGFR(EGFRcys)是GFR的替代标记物。为了确定eGFRcys比其eGFRcr低30%以上的癌症患者，与肾清除药物相关的治疗药物水平和不良事件(AEs)是否更高。这项队列研究分析了马萨诸塞州波士顿两个主要学术癌症中心的成年癌症患者。这些患者在2010年5月至2022年1月的同一天进行了肌酐和胱抑素C的检测。第一次同时测量eGFRcr和eGFRcys的日期被认为是基准日期。主要暴露是EGFR不一致，定义为eGFRcys比eGFRcr低30%以上。主要结果是在基线日期的90天内发生以下与药物相关的不良反应的风险：(1)超治疗万古霉素谷值大于30μg/mL，(2)甲氧普林-磺胺甲恶唑相关性高钾血症(>；5.5mEq/L)，(3)巴氯芬毒性作用，以及(4)超治疗地高辛水平(>；2.0 ng/mL)。对于次要结果，使用多变量COX比例风险回归模型来比较有或无EGFR不一致的患者的30天生存率。共有1869名成年癌症患者(平均年龄66[14]岁；948名男性[51%])同时进行了eGFRcys和eGFRcr测量。有543名患者(29%)的eGFRcys比其eGFRcr低30%以上。与eGFRcr一致的患者相比，eGFRcys低于其eGFRcr超过30%的患者更有可能发生药物相关的不良反应(定义为eGFRcr的30%以内的eGFRcys)，包括万古霉素水平超过30μg/mL(179例中43例[24%]vs7例[9%]；P = .01)，甲氧普林-磺胺甲恶唑相关性高钾(29例[22%]vs11例[12%]；P = .07)，巴氯芬毒性效应(5例19例[26%]vs0例；P = .19)，以及超治疗地高辛水平(7/24[29%]vs 0/10；P = .08)。万古霉素水平>30μg/mL的调整优势比为2.59(95%可信区间为1.08~7.03；P = 为0.04)。EGFRcys比其eGFRcr低30%以上的患者30天死亡率增加(调整后的危险比为1.98；95%可信区间为1.26-3.11；P = 为0.003)。这项研究的结果表明，在同时检测eGFRcys和eGFRcr的癌症患者中，eGFRcys比eGFRcr低30%以上的患者更容易发生超治疗药物水平和药物相关的不良反应。未来的前瞻性研究需要改进和个性化癌症患者的GFR估计和用药剂量。
This cohort study assesses the risk of supratherapeutic doses, hyperkalemia, toxic effects, and mortality among adults with cancer with lower serum creatinine–based than cystatin C–based estimated glomerular filtration rate. What are the consequences of discordance in serum creatinine–based estimated glomerular filtration rate (eGFRcr) vs cystatin C–based eGFR (eGFRcys) in patients with cancer? In this cohort study of 1869 adults with cancer, those with an eGFRcys that was more than 30% lower than their eGFRcr had an increased risk of supratherapeutic vancomycin levels, trimethoprim-sulfamethoxazole–related hyperkalemia, baclofen toxic effect, high digoxin levels, and increased risk of death within 30 days. Findings of this study suggest that medication-related adverse events occurred more commonly in patients whose eGFRcys was more than 30% lower than their eGFRcr, necessitating future studies to improve and personalize glomerular filtration rate estimation and medication dosing in patients with cancer. Serum creatinine–based estimated glomerular filtration rate (eGFRcr) may overestimate the glomerular filtration rate (GFR) in patients with cancer. Cystatin C–based eGFR (eGFRcys) is an alternative marker of GFR. To determine whether the therapeutic drug levels and adverse events (AEs) associated with renally cleared medications were higher in patients with cancer whose eGFRcys was more than 30% lower than their eGFRcr. This cohort study analyzed adult patients with cancer at 2 major academic cancer centers in Boston, Massachusetts. These patients had their creatinine and cystatin C measured on the same day between May 2010 and January 2022. The date of the first simultaneous eGFRcr and eGFRcys measurement was considered to be the baseline date. The primary exposure was eGFR discordance, defined as an eGFRcys that was more than 30% lower than the eGFRcr. The primary outcome was risk of the following medication-related AEs within 90 days of the baseline date: (1) supratherapeutic vancomycin trough level greater than 30 μg/mL, (2) trimethoprim-sulfamethoxazole–related hyperkalemia (>5.5 mEq/L), (3) baclofen toxic effect, and (4) supratherapeutic digoxin level (>2.0 ng/mL). For the secondary outcome, a multivariable Cox proportional hazards regression model was used to compare 30-day survival of those with vs without eGFR discordance. A total of 1869 adult patients with cancer (mean [SD] age, 66 [14] years; 948 males [51%]) had simultaneous eGFRcys and eGFRcr measurement. There were 543 patients (29%) with an eGFRcys that was more than 30% lower than their eGFRcr. Patients with an eGFRcys that was more than 30% lower than their eGFRcr were more likely to experience medication-related AEs compared with patients with concordant eGFRs (defined as eGFRcys within 30% of eGFRcr), including vancomycin levels greater than 30 μg/mL (43 of 179 [24%] vs 7 of 77 [9%]; P = .01), trimethoprim-sulfamethoxazole–related hyperkalemia (29 of 129 [22%] vs 11 of 92 [12%]; P = .07), baclofen toxic effects (5 of 19 [26%] vs 0 of 11; P = .19), and supratherapeutic digoxin levels (7 of 24 [29%] vs 0 of 10; P = .08). The adjusted odds ratio for vancomycin levels more than 30 μg/mL was 2.59 (95% CI, 1.08-7.03; P = .04). Patients with an eGFRcys more than 30% lower than their eGFRcr had an increased 30-day mortality (adjusted hazard ratio, 1.98; 95% CI, 1.26-3.11; P = .003). Results of this study suggest that among patients with cancer with simultaneous assessment of eGFRcys and eGFRcr, supratherapeutic drug levels and medication-related AEs occurred more commonly in those with an eGFRcys more than 30% lower than their eGFRcr. Future prospective studies are needed to improve and personalize GFR estimation and medication dosing in patients with cancer.
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在肿瘤患者中，在恶性肿瘤和GFR估计值的可比性中评估胱抑素C的评估。
影响因子：
1.9
作者：
Jones M;Denieffe S;Griffin C;Tinago W;Fitzgibbon MC
通讯作者：
Fitzgibbon MC
DOI：
10.1056/nejmoa1114248
发表时间：
2012-07-05
期刊：
The New England journal of medicine
影响因子：
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作者：
Inker LA;Schmid CH;Tighiouart H;Eckfeldt JH;Feldman HI;Greene T;Kusek JW;Manzi J;Van Lente F;Zhang YL;Coresh J;Levey AS;CKD-EPI Investigators
通讯作者：
CKD-EPI Investigators
影响因子：
2.6
作者：
Cheong, Minseon;Lee, Jongmin;Kim, Soon Bae
通讯作者：
Kim, Soon Bae
影响因子：
2.8
作者：
Critchley, JAJH;Critchley, LAH
通讯作者：
Critchley, LAH
DOI：
10.1053/j.ajkd.2022.05.011
发表时间：
2022-12
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
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作者：
通讯作者：
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