我们的结果证明，含乙醛酸的直发剂是导致草酸钙沉积、诱发肾病的原因。考虑到外用乙醛酸具有潜在肾毒性，应避免使用含该化合物的产品，我们建议将其退市。
撰文 | 燕小六
“我们建议这类产品退市。”近日，《新英格兰医学杂志》（NEJM）发表法国学者通讯文章，直指化学直发膏剂的安全问题。
文章称，一名年轻女性在两年内出现3次急性肾损伤。询问病史发现，其发病和使用特定直发剂、拉直头发有关。动物实验证实，该直发剂含有10%乙醛酸，是诱发急性肾损伤的罪魁祸首。
近年来，化学直发剂造成急性肾损伤的讨论、文献频出。有人因此出现急性草酸性肾病，需要住院、透析治疗。
接连3回！染发当天急性肾损伤
前述NEJM文章由法国马赛de la Conception医院Thomas Robert等人撰写。根据媒体报道，研究人员最初关注到这个病例，是因为其中有太多“巧合”。
该名女性26岁，过往身强体健。2020年6月、2021年4月和2022年7月，她3次因呕吐、腹泻、发热和背痛等就医，都被诊断为急性肾损伤。
实验室检查显示，她的血浆肌酐水平升高。尿检发现血液和白细胞，但无蛋白尿和感染。计算机断层扫描（CT）显示无阻塞性尿路病变迹象。
神奇的是，每一次病发后，她的肾功能会迅速好转。最后一次随访显示，其血浆肌酐水平正常（0.78mg/dL）。全外显子组测序分析结果呈阴性。
研究团队复盘病史，找到端倪：患者每一次出现急性肾损伤的当天，都去过同一家理发店，做头发拉直。
患者自述，拉直发时，她的头部有烧灼感。当日就医的记录显示，其血浆肌酐水平飙升至约2.0mg/dL。
事后证实，理发店在拉直头发的过程中会使用一款直发膏，其中含10%乙醛酸。这是一种相对较新的烫发产品，能使角蛋白变硬，从而达到拉直头发的功效。过往，美发行业曾在直发产品中使用甲醛或亚甲基二醇（会释放甲醛）成分，因有致癌风险被弃用。
一名既往无健康问题的女性患者在两年内，3次诊断为急性肾损伤，每次都是在拉直头发后立即发病。虚线表示未接受随访的时间段。图源/NEJM
“不信邪的人”
这两年，乙醛酸伤肾的消息并不少见。
2023年1月5日，以色列政府宣布禁用含有乙醛酸成分的烫发产品，并要求消费者网购时仔细看成分表。就在此前一天，肾病领域知名期刊AJKD发表该国耶路撒冷希伯来大学研究，称含有乙醛酸的直发剂会导致急性肾损伤。
研究团队追踪了2019—2022年该国14所医学中心、共26名严重急性肾损伤患者，平均年龄为28.5岁（14-58岁）。其中3人需要透析治疗。
这些患者的共同点之一是，发生急性肾损伤前刚做过头发拉直。其二，症状类似，主要包括恶心、呕吐和腹痛，有10人出现头部皮疹。其三，体内草酸钙水平过高。
在26人中，有7人做了肾活检，均提示肾小管损伤迹象。具体来看，6人被查出肾小管内草酸钙沉积，另1人出现肾小管微钙化。
研究还特别提到2名患者。经过治疗，两人不信邪地又去做了直发，结果又因肾损伤被送进医院。
耶路撒冷希伯来大学团队推测，这很可能是直发剂中的乙醇酸及其衍生物通过皮肤吸收，在体内代谢成草酸盐。过量的草酸盐沉积于肾脏，就会引发肾脏功能急剧下降。
时间再往前推。2021年、2022年，不同期刊都有病例报告称，明明用的是不含甲醛的直发剂，却导致患者急性肾损伤。再去查成分表，发现里面含有乙醇酸。
染发也不安全。2021年，BMJ Case Reports发布一则病例报告，一位18岁抗肾小球基底膜病患者经过血浆置换、激素冲击、环磷酰胺治疗后，病情获得缓解。她开开心心地出院，去染了个红头发。结果出院没2周，她的肾病迅速复发。医生思来想去，认为复发原因可能是用了染发剂。
小老鼠又成功臣
在过往的烫染发和肾损伤相关报告中，研究人员苦于无法提供确凿证据。耶路撒冷希伯来大学团队在其文章中就表示，作用机理暂是推测。
本次NEJM发表法国学者文章，填补了这块空白。
为探讨潜在机制，研究人员做了一个动物对照实验。他们在5只实验组小鼠的背部涂抹直发膏，给对照组的5只小鼠涂抹凡士林。
第二天的尿检显示，实验组小鼠的尿液内有细长的一水草酸钙晶体，与乙二醇中毒后观察到的晶体形状相似。涂抹直发剂28小时后，实验组小鼠的血浆肌酐水平显著升高。在实验组中，进行肾脏三维CT扫描，发现与肾小管形状相似的致密一水草酸钙沉积物。
这些，在对照组小鼠中没有看到。
小鼠肾脏三维计算机断层扫描模型的代表性投影图。图D为对照组，暴露于凡士林；图E为实验组，暴露于直发膏剂。钙化的高密度区以红色显示。图源/NEJM
Thomas Robert等人解释，2013年2月至今，烫染产品无需进行动物实验即可在法国上市。“我们必须找到一种新方法，来检测那些应用于皮肤的产品及其相关毒性。而且，似乎有必要评估全身吸收以及肝、肾和心血管毒性等。”
研究团队还表示，理论上不让直发膏剂接触头皮、减少使用频次，都能降低肾毒性。“美发师也会建议，涂抹直发剂应该距离头皮0.5厘米左右。但大多数去做直发的人都追求完全直顺的效果。那就得贴着头皮涂抹。”
“我们的结果证明，含乙醛酸的直发剂是导致草酸钙沉积、诱发肾病的原因。考虑到外用乙醛酸具有潜在肾毒性，应避免使用含该化合物的产品，我们建议将其退市。”研究人员在NEJM文章结尾处如是写道。
参考文献：
1.Kidney Injury and Hair-Straightening Products Containing Glyoxylic Acid. N Engl J Med. 2024;390:1147-1149. DOI:10.1056/NEJMc2400528
2.Acute Kidney Injury and Hair-Straightening Products: A Case Series. Am J Kidney Dis. 2023 Jul;82(1):43-52.e1. doi: 10.1053/j.ajkd.2022.11.016
3.Recent use of formaldehyde-‘free’ hair straightening product and severe acute kidney injury . Clinical Kidney Journal. Volume 14, Issue 5, May 2021, Pages 1469–1471. doi.org/10.1093/ckj/sfaa272
4.Acute Kidney Injury following Exposure to Formaldehyde-Free Hair-Straightening Products. Case Rep Nephrol. Dial (2022) 12 (2): 112–116. doi.org/10.1159/000525567
5.Relapse of treated anti-GBM disease following hair dye use. BMJ Case Rep. 2021; 14(4): e240543. doi: 10.1136/bcr-2020-240543
来源：医学界
：王 晓
：赵 静
*“医学界”力求所发表专业、可靠，但不对的准确性做出承诺；请相关各方在采用或以此作为决策依据时另行核查。
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#10aeff;--weui-INDIGO: #1196ff;--weui-PURPLE: #8183ff;--weui-WHITE: rgba(255, 255, 255, .8);--weui-LINK: #7d90a9;--weui-TEXTGREEN: #259c5c;--weui-FG: #fff;--weui-BG: #000;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px){body:not(.pages_skin_pc) .wx-root,body:not(.pages_skin_pc) body{--appmsgExtra-BG: #F7F7F7}}@media screen and (min-width:1024px){body:not(.pages_skin_pc) .wx-root[data-weui-theme=dark],body:not(.pages_skin_pc) body[data-weui-theme=dark]{--weui-BG-0: #111;--weui-BG-1: #1e1e1e;--weui-BG-2: #191919;--weui-BG-3: #202020;--weui-BG-4: #404040;--weui-BG-5: #2c2c2c;--weui-FG-0: rgba(255, 255, 255, .8);--weui-FG-HALF: rgba(255, 255, 255, .6);--weui-FG-1: rgba(255, 255, 255, .5);--weui-FG-2: rgba(255, 255, 255, .3);--weui-FG-3: rgba(255, 255, 255, .1);--weui-FG-4: rgba(255, 255, 255, .15);--weui-FG-5: rgba(255, 255, 255, .1);--weui-RED: #fa5151;--weui-ORANGERED: #ff6146;--weui-ORANGE: #c87d2f;--weui-YELLOW: #cc9c00;--weui-GREEN: #74a800;--weui-LIGHTGREEN: #3eb575;--weui-BRAND: #07c160;--weui-BLUE: #10aeff;--weui-INDIGO: #1196ff;--weui-PURPLE: #8183ff;--weui-WHITE: rgba(255, 255, 255, .8);--weui-LINK: #7d90a9;--weui-TEXTGREEN: #259c5c;--weui-FG: #fff;--weui-BG: #000;--weui-TAG-TEXT-RED: rgba(250, 81, 81, .6);--weui-TAG-BACKGROUND-RED: rgba(250, 81, 81, .1);--weui-TAG-TEXT-ORANGE: rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, 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rgba(250, 157, 59, .6);--weui-TAG-BACKGROUND-ORANGE: rgba(250, 157, 59, .1);--weui-TAG-TEXT-GREEN: rgba(6, 174, 86, .6);--weui-TAG-BACKGROUND-GREEN: rgba(6, 174, 86, .1);--weui-TAG-TEXT-BLUE: rgba(16, 174, 255, .6);--weui-TAG-BACKGROUND-BLUE: rgba(16, 174, 255, .1);--weui-TAG-TEXT-BLACK: rgba(255, 255, 255, .5);--weui-TAG-BACKGROUND-BLACK: rgba(255, 255, 255, .05)}}@media screen and (min-width:1024px) and (prefers-color-scheme:dark){body:not(.pages_skin_pc) .wx-root:not([data-weui-theme=light]),body:not(.pages_skin_pc) body:not([data-weui-theme=light]){--appmsgExtra-BG: #121212}}@media(prefers-color-scheme:dark){body:not([data-weui-theme=light]).my_comment_empty_data{background-color:#111}}body,.wx-root{--weui-BG-6: rgba(0, 0, 0, .05);--weui-ACTIVE-MASK: rgba(0, 0, 0, .05)}body,.wx-root{--weui-REDORANGE: #ff6146;--weui-BG-0: #ededed;--weui-BG-1: #f7f7f7;--weui-BG-2: #fff;--weui-BG-3: #f7f7f7;--weui-BG-4: #4c4c4c;--weui-BG-5: #fff;--weui-FG-0: rgba(0, 0, 0, .9);--weui-FG-HALF: rgba(0, 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