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急性腎障害バイオマーカーの臨床応用

松浦, 亮 東京大学 DOI:10.15083/0002002417

2021.10.13

概要

急性腎障害(Acute Kidney Injury, AKI)は集中治療領域において頻度の高い疾患であり、死亡率も高いため、早期診断を目的として複数のバイオマーカーが開発されてきたが、その診断精度は一定しない。一方で、臨床で頻用されるフロセミドや血清クレアチニンを用いてAKIを予測するマーカーがある。ひとつはフロセミドに対して反応した尿量を指標としてAKIを予測する方法であり、もう一つはRenal angina index(RAI)とよばれる方法である。本研究ではこれら臨床で頻用されるパラメータ(血清クレアチニン、尿量)を用いた指標とバイオマーカーを組み合わせることによる重症AKIおよび予後の予測が向上するかを検討した。最初にフロセミドとそれに反応する尿量で重症AKIを予測しうるか検討した。フロセミドに対して反応した尿量を指標したマーカーをフロセミド反応性と定義し、フロセミド投与後2時間での尿量をフロセミド投与量で割った値とした。ICU入室時にAKIバイオマーカーである血漿NGALを測定しかつフロセミドを投与したICU患者を解析対象とした。これらの患者はAKIを発症していない、もしくはKDIGO分類でAKI stage 1, 2を発症した患者のみを含め、AKI stage 3を発症した患者は除外した。アウトカムは入室日してから1週間以内にAKI stage 3に進展することとした。結果は95人のICU患者が解析対象となり、18人がAKI stage 3に進展した。Receiver operating curve analysisではフロセミド反応性、血漿NGALのAUCは0.87(95%信頼区間: 0.73-0.94), 0.80(0.67-0.88)であった。血漿NGAL<142ng/mLにおいてはAKI stage 3への進展した患者は一人のみであった。そのためAKI stage 3への進展をスクリーニングするには血漿NGALで十分と考えた。次に血漿NGAL≥142ng/mLであった51人の患者でのフロセミド反応性の有効性について検討した。ROC解析ではAKI stage 3進展をアウトカムとしたフロセミド反応性のAUCは0.84(0.67-0.94)であった。

 次にRAIの有用性について検討した。この研究は日本とタイでの観察研究のサブ解析である。対象患者はAKIを発症していない、もしくはAKI stage 1のICU患者とした。はじめはRAIを対象となったすべての患者に対してICU入室翌日に計算した。次の解析としてベースライン血清クレアチニンのわかる病棟からICUに入室した患者を対象とし、RAIの計算をICU入室日とした。AKIバイオマーカーとして尿L-FABPを用い、RAIと組み合わせてアウトカムの予測が向上するか検討した。アウトカムは48時間後にAKI stage 2/3に進展していることとした。263人の患者が対象となり、22人がアウトカムを達した。ROC解析ではRAIのアウトカム予測能はAUCは0.63(0.53–0.73)であった。病棟からの入室した患者に限るとAUCは0.73(0.58-0.87)であった。さらにL-FABPと組み合わせた場合はアウトカムの予測能はAUC0.79(0.58–0.91)と改善した。

 臨床で頻用されるパラメータを用いた指標とバイオマーカーを組み合わせることで、重症AKIへの進展リスクをより層別化できた。これらの指標を用いることで個々の症例に応じた適切なAKI管理ができる可能性がある。

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