Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, IL.
Baylor University Medical Center, Dallas, TX.
Hepatology. 2019 Oct;70(4):1349-1359. doi: 10.1002/hep.30667. Epub 2019 May 28.
In patients with end-stage liver disease, the ability to predict recovery of renal function following liver transplantation (LT) remains elusive. However, several important clinical decisions depend on whether renal dysfunction is recoverable after LT. We used a cohort of patients undergoing LT to independently validate a published pre-LT model predictive of post-transplant renal recovery (Renal Recovery Assessment at Liver Transplant [REVERSE]: high osteopontin [OPN] and tissue inhibitor of metalloproteinases-1 [TIMP-1] levels, age < 57, no diabetes). Serum samples pre-LT and 4-12 weeks post-LT (n = 117) were analyzed for kidney injury proteins from three groups of recipients: (1) estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m prior to and after LT (irreversible acute kidney injury [AKI]), (2) eGFR < 30 mL/minute/1.73 m prior to LT and >50 mL/minute/1.73 m after LT (reversible AKI [rAKI]) (3) eGFR > 50 mL/minute/1.73 m prior to and after LT (no AKI). In patients with elevated pre-LT serum levels of OPN and TIMP-1, recovery of renal function correlated with decreases in the level of both proteins. At 4 weeks post-LT (n = 77 subset), the largest decline in OPN and TIMP-1 was seen in the rAKI group. Validation of the REVERSE model in this independent data set had high area under the curve (0.78) in predicting full post-LT renal recovery (sensitivity 0.86, specificity 0.6, positive predictive value 0.81, negative predictive value 0.69). Our eGFR findings were confirmed using measured GFR. Conclusion: The REVERSE model, derived from an initial training set combining plasma biomarkers and clinical characteristics, demonstrated excellent external validation performance characteristics in an independent patient cohort using serum samples. Among patients with kidney injury pre-LT, the predictive ability of this model may prove beneficial in clinical decision-making both prior to and following transplantation.
在终末期肝病患者中，预测肝移植 (LT) 后肾功能恢复的能力仍然难以捉摸。然而，几项重要的临床决策取决于 LT 后肾功能是否可恢复。我们使用 LT 患者队列来独立验证一个已发表的 LT 前预测移植后肾功能恢复的模型 (肝移植后肾功能恢复评估 [REVERSE]：高骨桥蛋白 [OPN] 和金属蛋白酶组织抑制剂-1 [TIMP-1] 水平高，年龄 <57 岁，无糖尿病)。分析了三组接受者 LT 前和 LT 后 4-12 周的血清样本中的肾脏损伤蛋白：(1)eGFR<30 mL/min/1.73 m 之前和之后 LT (不可逆转的急性肾损伤 [AKI])，(2)eGFR<30 mL/min/1.73 m 之前 LT 和 >50 mL/min/1.73 m 之后 LT (可逆 AKI [rAKI])，(3)eGFR>50 mL/min/1.73 m 之前和之后 LT (无 AKI)。在 OPN 和 TIMP-1 血清水平升高的患者中，肾功能的恢复与两种蛋白水平的降低相关。在 LT 后 4 周 (n=77 亚组)，rAKI 组观察到 OPN 和 TIMP-1 下降最大。在这个独立数据集验证的 REVERSE 模型具有较高的曲线下面积 (0.78)，可预测完全 LT 后肾功能恢复 (灵敏度 0.86，特异性 0.6，阳性预测值 0.81，阴性预测值 0.69)。我们的 eGFR 发现使用测量的 GFR 得到了证实。结论：从最初的训练集结合血浆生物标志物和临床特征推导而来的 REVERSE 模型，在使用血清样本的独立患者队列中表现出优异的外部验证性能特征。在 LT 前有肾脏损伤的患者中，该模型的预测能力可能在移植前和移植后对临床决策都有帮助。
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