PPIs可能增加慢性、隐性肾脏损伤的风险--双语

PPIs May Increase Risk for Chronic, Silent Kidney Damage　
PPIs可能增加慢性、隐性肾脏损伤的风险

Nicola M. Parry, DVM
http://www.medscape.com/viewarticle/876199

Among new users of PPIs, more than half of those who go on to develop chronic kidney damage while taking the medication have no signs of acute kidney injury (AKI) beforehand, a new study shows.
有一项新的研究显示，新近服用质子泵抑制剂（PPIs）的患者中，有超过半数人在服药的同时会发生慢性肾损害，而事先没有任何急性肾损伤（AKI）的迹象。

Yan Xie, MPH, from Veterans Affairs (VA) Saint Louis Health Care System, Missouri, and colleagues published the results of their study online February 22 in Kidney International.
来自密苏里州圣路易斯卫生保健系统退伍军人事务所（VA）的Yan Xie, MPH，和他的同事公布了他们的研究结果，在线发表于2 月 22 日《Kidney International》上。　

"We show that among new users of acid suppression therapy, incident PPI users have increased risk of chronic renal outcomes including incident chronic kidney disease (CKD), CKD progression, and end-stage renal disease (ESRD) in the absence of intervening AKI," the authors write.
作者写道：“我们发现新近进行抑酸治疗的患者中，使用PPI者，其发生慢性肾疾病的风险增加，包括慢性肾脏病（CKD）、慢性肾病进展和终末期肾病（ESRD），而没有AKI的发生”。

"Reliance on antecedent AKI as a warning sign to guard against risk of developing CKD and progression to ESRD among PPI users is not sufficient as a sole risk mitigation strategy. Exercising vigilance in PPI use — even in the absence of AKI — and careful attention to kidney function in PPI users may be a reasonable approach."
“在PPI使用者中，依赖于提前发生的AKI以防患CKD和进展到终末期肾病的警告标志，并将其作为唯一的风险缓解策略是不够的。即使没有AKI发生，PPI服用者在使用PPI时保持警觉，并仔细留意肾功能可能是一个合理的方法。”

PPI treatment is known to increase the risk for AKI, acute interstitial nephritis, and CKD. However, whether PPI use is tied to a greater risk for chronic kidney damage in the absence of an earlier episode of AKI has been unclear.
众所周知，PPI治疗可增加AKI、急性间质性肾炎和CKD的风险。然而，PPI使用是否与无早期AKI发作的慢性肾损伤这类更大的风险有关一直不清楚。

Xie and colleagues therefore investigated whether PPI-related CKD and other chronic renal outcomes are mediated only by the occurrence of AKI.
因此，Xie和他的同事对PPI相关的慢性肾病和其他慢性肾病是否仅通过AKI发生介导进行了研究。

Using the US Department of VA databases, the researchers analyzed data on 125,596 new users of PPIs and 18,436 new users of histamine H2 receptor agonists (H2 blockers). They followed the patients for 5 years to compare renal outcomes between the two groups.
利用美国VA部门的数据库，研究人员分析了125,596名新近服用PPIs和18,436名新近服用组胺H2受体激动剂（H2 受体阻滞剂）的患者数据。他们跟踪了患者5年的数据，并比较了两组的肾脏问题。

Compared with new users of H2 blockers, new users of PPIs had a greater risk of having an estimated glomerular filtration rate (eGFR) less than 60 mL/minute/1.73 m2 (hazard ratio [HR], 1.19; 95% confidence interval [95% CI], 1.15 - 1.24), incident CKD (HR, 1.26; 95% CI, 1.20 - 1.33), a greater than 30% decrease in eGFR (HR, 1.22; 95% CI, 1.16 - 1.28), and ESRD or a greater than 50% decrease in eGFR (HR, 1.30; 95% CI, 1.15 - 1.48), after adjusting for demographic factors and numerous comorbidities.
与新近服用H2受体阻滞剂的患者相比，新近服用PPI存在更大的风险，在进行人口因素和诸多并发症的调整后，出现估计肾小球滤过率（eGFR） 低于60mL/min/1.73m2（HR，1.19； 95% CI，1.15 - 1.24），发生CKD（HR，1.26；95% CI，1.20 - 1.33），eGFR跌幅超过30%（HR，1.22；95% CI，1.16 - 1.28），ESRD或eGFR超过50%以上跌幅（HR，1.30；95%CI，1.15 - 1.48）。

In addition, 18.24% of new PPI users developed AKI during this time compared with 12.67% of new users of H2 blockers.
此外，新近使用PPI患者中有18.24%在这段时间里发生了AKI，而新近使用H2受体阻滞剂的患者中为12.67%。

When the researchers excluded those patients with AKI from their multivariable models, PPI users still had an excess risk for chronic renal outcomes compared with those taking H2 blockers. Specifically, their risk was 22% higher for incident eGFR less than 60 mL/minute/1.73 m2 (HR, 1.22; 95% CI, 1.17 - 1.27), 29% higher for CKD (HR, 1.29; 95% CI, 1.22 - 1.36), 26% higher for a greater than 30% decrease in eGFR (HR, 1.26; 95% CI, 1.19 - 1.32), and 35% higher for ESRD or a greater than 50% decrease in eGFR (HR, 1.35; 95% CI, 1.19 - 1.53).
当研究人员在多变量模型中排除这些AKI患者后，相比于那些服用H2受体阻滞剂的患者，服用PPI的患者仍然会有更高的慢性肾病风险。具体而言，出现eGFR低于60 mL/min/1.73 m2的风险高出22%（HR，1.22；95 %CI，1.17 - 1.27），发生CKD高出29%（HR，1.29；95 %CI，1.22 - 1.36），eGFR超过30%的跌幅高出26%（HR，1.26；95%CI，1.19 - 1.32），ESRD或eGFR超过50%以上跌幅高出35%（HR，1.35；95 %CI，1.19 - 1.53）。

In each case, the researchers calculated that slightly less than half (44.7% - 46.7%) of the risk for the chronic kidney conditions was mediated by AKI.
在不同情况下，研究人员计算得出略低于半数（44.7%-46.7%）的慢性肾病的风险条件是通过AKI介导的。

These results suggest that PPI use is associated with increased risk for chronic renal damage in patients who have not experienced AKI beforehand.
这些结果表明，在事先未曾经历AKI的患者中，使用PPI与慢性肾损害风险增加有关。

In an interview with Medscape Medical News, Robert Albright, DO, chair of nephrology and hypertension at the Mayo Clinic in Rochester, Minnesota, was more cautious in drawing conclusions from the data.
在Medscape医学新闻做采访时，明尼苏达州罗切斯特市梅奥诊所的肾脏病和高血压病主席Robert Albright针对从这些数据得出结论更为谨慎。

He noted that compared with the group using H2 blockers, PPIs users had many more comorbidities, which are also associated with renal outcomes. "And we do not get any information on other medications or non-AKI events which might have occurred, which also could have been associated with poor, long-term renal outcomes." Other important information is also lacking, he said, including the duration of PPI treatment.
他指出，相比于使用H2受体阻滞剂组的患者，使用质子泵抑制剂患者会出现更多的并发症，这也与肾病相关。“我们没有得到可能与不良、长期肾病有关的其他药物或可能已经发生的非AKI事件的任何信息。” 他还补充说，尚缺乏其他重要的信息，包括PPI治疗的持续时间。

In addition, Dr Albright highlighted that the study did not include a comparison group of non-PPI users in this VA cohort, with similar comorbidities. "It is a retrospective white VA cohort, with the inherent biases which prevent generalizability."
此外，Albright博士特别强调，该研究没有在VA数据库人群中，选择非PPI使用者且有类似并发症的患者作为对照组，“这是一项针对VA数据库中白色人种的回顾性研究，带有固有偏倚，不具普遍性”。

Nevertheless, Dr Albright stressed the benefit of directing attention to PPI use, which has become routine, rather than medically indicated, "particularly with the increased risks of Clostridium difficile infection with PPI use as well," he concluded.
然而，Albright博士也强调了关注PPI使用的益处，PPI使用已是司空见惯，超越了医学上的适应症，他指出“尤其是PPI使用可以增加艰难梭菌感染的风险”。

This study was funded by a grant from the US Department of Veterans Affairs. The authors and Dr Albright have disclosed no relevant financial relationships.
Kidney Int. Published online February 22, 2017.
此项研究是由美国退伍军人事务部资助。作者和Albright博士披露没有相关财务关系。
2017.2.22在线发表于Kidney Int.

全文链接
http://www.medimpact.com.cn/jjfa/yy/gldp/252965.shtml

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