非奈利酮对2型糖尿病、慢性肾脏病及肝脏脂肪变性和纤维化标志物改变患者的疗效：FIDELITY亚组分析
Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis.
作者信息
Perakakis Nikolaos, Bornstein Stefan R, Birkenfeld Andreas L, Linkermann Andreas, Demir Münevver, Anker Stefan D, Filippatos Gerasimos, Pitt Bertram, Rossing Peter, Ruilope Luis M, Kolkhof Peter, Lawatscheck Robert, Scott Charlie, Bakris George L
机构信息
University Study Center for Metabolic Diseases, Department of Internal Medicine III, Carl Gustav Carus University Clinic, TU Dresden, Dresden, Germany.
University Hospital and Faculty of Medicine, TU Dresden, Dresden, Paul Langerhans Institute Dresden (PLID), Helmholtz Center Munich, Dresden, Germany.
出版信息
Diabetes Obes Metab. 2024 Jan;26(1):191-200. doi: 10.1111/dom.15305. Epub 2023 Oct 10.
AIM
Investigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis.
MATERIALS AND METHODS
Post hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis-4 (FIB-4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma-glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure.
RESULTS
ALT, aspartate aminotransferase and gamma-glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB-4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB-4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively).
CONCLUSIONS
Finerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB-4 scores who were at high risk of developing cardiovascular complications.
目的
研究非奈利酮对慢性肾脏病合并2型糖尿病患者肝功能、心血管和肾脏复合结局的影响，并根据其肝脂肪变性、炎症和纤维化风险进行分层。
材料与方法
事后分析根据肝纤维化和酶水平对患者（N = 13026）进行分层：脂肪变性高风险（肝脂肪变性指数>36）；转氨酶升高[男性丙氨酸转氨酶（ALT）>33，女性>25 IU/L]；以及纤维化-4（FIB-4）指数评分>3.25、>2.67和>1.30。通过ALT、天冬氨酸转氨酶和γ-谷氨酰转移酶的变化评估肝酶。复合肾脏结局定义为肾衰竭的发生、持续估计肾小球滤过率从基线下降≥57%且持续≥4周或肾脏死亡。复合心血管结局定义为心血管死亡、非致死性心肌梗死、非致死性中风或因心力衰竭住院。
结果
治疗组之间的ALT、天冬氨酸转氨酶和γ-谷氨酰转移酶水平一致，且在整个过程中保持稳定。无论肝检查结果如何，非奈利酮始终降低复合肾脏结局的风险。较高的FIB-4评分与复合心血管结局的较高发生率相关。在FIB-4亚组中，与安慰剂相比，非奈利酮使复合心血管结局的风险降低了52%（>3.25）、39%（>2.67）和24%（>1.30）（交互作用的p值分别为0.01、0.13和0.03）。
结论
非奈利酮对慢性肾脏病合并2型糖尿病患者的肝脏参数具有中性影响。非奈利酮在肝检查结果异常的患者中显示出强大且一致的肾脏益处，即使在FIB-4评分较高且发生心血管并发症风险较高的患者中也具有显著的心血管益处。
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