Baylor University Medical Center Dallas TX Baylor Scott & White Research Institute Dallas TX Division of Nephrology and HypertensionDepartment of MedicineKeck School of Medicine University of Southern California Los Angeles CA GI/Liver Transplant Unit Institut de Malalties Digestives i Metaboliques, Hospital Clinic Barcelona Spain Faculty of Medicine University of Barcelona Barcelona Spain Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD) Barcelona Spain.
Liver Transpl. 2022 Mar;28(3):466-482. doi: 10.1002/lt.26344. Epub 2021 Dec 17.
Acute kidney injury (AKI) and chronic kidney disease (CKD) are important drivers of morbidity and mortality in patients with cirrhosis before and after liver transplantation (LT). In this review, we examine the role of novel kidney biomarkers for early recognition of kidney injury. Studies are limited by lack of reference standards, heterogeneous definitions of outcomes and biomarker cutoffs, and inconsistent diagnostic performance. Overall, a change in biomarker is more relevant than an absolute cutoff. Cystatin C and urinary neutrophil gelatinase-associated lipocalin (uNGAL) are the most studied candidate biomarkers and identify AKI or progression of AKI earlier than serum creatinine (sCr). Kidney injury molecule 1 and liver-type fatty acid-binding protein (L-FABP) also show potential. NGAL and interleukin 18 may play a role in differentiating acute tubular necrosis from other forms of AKI. Combining novel biomarkers with the Model for End-Stage Liver Disease score may assist prognosis. Persistent elevations in select markers (eg, NGAL) can portend irreversible injury. Several pretransplantation markers (including sCr) predict posttransplantation kidney dysfunction. Pretransplantation assessment of clinical factors (eg, age, diabetes) and novel markers (osteopontin and tissue inhibitor of metalloproteinases 1 [TIMP-1]) may predict renal kidney recovery after LT. Intraoperative changes in biomarkers predict early post-LT AKI. Prediction of CKD remains difficult, although a combination of biomarkers (eg, beta-2 microglobulin, CD40) is promising. Novel biomarkers have yet to replace sCr in guideline-based evaluation and management of kidney dysfunction in patients with cirrhosis. We propose a theoretical framework for practical incorporation of these biomarkers that considers patient characteristics (risk for irreversible injury), markers of functional and structural change, and assessment of the AKI-CKD continuum to identify patients at the highest risk for progressive kidney disease before and after LT.
急性肾损伤（AKI）和慢性肾脏病（CKD）是肝移植（LT）前后肝硬化患者发病率和死亡率的重要驱动因素。在这篇综述中，我们研究了新型肾脏生物标志物在早期识别肾脏损伤中的作用。这些研究受到缺乏参考标准、结局和生物标志物截止值的定义不一致以及诊断性能不一致等因素的限制。总体而言，生物标志物的变化比绝对截止值更相关。胱抑素 C 和尿中性粒细胞明胶酶相关脂质运载蛋白（uNGAL）是研究最多的候选生物标志物，比血清肌酐（sCr）更早识别 AKI 或 AKI 的进展。肾脏损伤分子 1 和肝型脂肪酸结合蛋白（L-FABP）也显示出潜力。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和白细胞介素 18（IL-18）可能在区分急性肾小管坏死与其他形式的 AKI 方面发挥作用。将新型生物标志物与终末期肝病模型评分相结合可能有助于预后。选择标志物（如 NGAL）的持续升高可能预示着不可逆转的损伤。一些移植前标志物（包括 sCr）预测移植后肾功能障碍。移植前评估临床因素（如年龄、糖尿病）和新型标志物（骨桥蛋白和金属蛋白酶组织抑制剂 1 [TIMP-1]）可能预测 LT 后肾脏的恢复情况。生物标志物的术中变化预测 LT 后早期 AKI。尽管生物标志物（如β-2 微球蛋白、CD40）的组合具有前景，但 CKD 的预测仍然困难。新型生物标志物尚未取代 sCr 在肝硬化患者基于指南的肾功能障碍评估和管理中。我们提出了一个理论框架，用于实际纳入这些生物标志物，该框架考虑了患者特征（不可逆损伤的风险）、功能和结构变化的标志物，以及 AKI-CKD 连续体的评估，以识别 LT 前后进展性肾脏疾病风险最高的患者。
