Vasan Senthil K, Chinnadurai Rajkumar, Rengarajan Sharmilee, Green Darren, Alderson Helen, Vuilleumier Nicolas, Kalra Philip A
Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Manchester, UK,
Donal O'Donoghue Renal Research Centre & Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford, UK,
Am J Nephrol. 2025 Jun 24:1-16. doi: 10.1159/000546489.
Cardiac biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin-T (Hs-cTnT) are good prognostic indicators of long-term clinical cardiovascular outcomes in patients with chronic kidney disease (CKD). However, the clinical utility of combined biomarkers in predicting death and cardio-renal outcomes in patients with CKD remains unclear. This study examined the prognostic accuracy and incremental value of NT-proBNP and Hs-cTnT for all-cause mortality, major adverse cardiovascular event (MACE), and end-stage kidney disease (ESKD) in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients.
Data from 1,946 individuals with NDD-CKD prospectively included in the Salford Kidney Study were used to investigate the associations between NT-proBNP and Hs-cTnT with study endpoints. Hazard ratio or sub-hazard ratio and 95% confidence intervals (95% CIs) were estimated using multivariate Cox-regression and competing risk models. The discriminatory power of NT-proBNP and Hs-cTnT along with kidney biomarkers (eGFR and uACR) and Framingham risk score (FRS) were calculated using Harrell's C-index. Endpoint-specific risk scores were generated using regression coefficients obtained in a training dataset and confirmed in a validation one.
During median follow-up of 71.5 months, 931 (47.8%) deaths, 553 (28.4%) MACE, and 554 (28.5%) ESKD events occurred. Baseline NT-proBNP and Hs-cTnT elevations were associated with significant increased risk of mortality, MACE, and ESKD independently of FRS. Combining NT-proBNP, Hs-cTnT, and FRS yielded the highest prognostic accuracy for all-cause mortality and MACE (respective C-statistics: 0.713; 95% CI: 0.695-0.731, and 0.697; 95% CI: 0.673-0.721), while combining NT-proBNP and Hs-cTnT with eGFR and uACR performed best at predicting ESKD (C-statistics: 0.821; 95% CI: 0.786-0.826).
In NDD-CKD patients, NT-proBNP and Hs-cTnT are predictors of all-cause mortality, MACE, and ESKD, independently of eGFR and uACR. Combining NT-proBNP and Hs-cTnT with eGFR and uACR outperformed risk prediction for ESKD compared to kidney biomarkers used alone or in combination.
心脏生物标志物、N末端B型利钠肽原（NT-proBNP）和高敏心肌肌钙蛋白T（Hs-cTnT）是慢性肾脏病（CKD）患者长期临床心血管结局的良好预后指标。然而，联合生物标志物在预测CKD患者死亡和心肾结局方面的临床效用仍不明确。本研究探讨了NT-proBNP和Hs-cTnT对非透析依赖型慢性肾脏病（NDD-CKD）患者全因死亡率、主要不良心血管事件（MACE）和终末期肾病（ESKD）的预后准确性和增量价值。
来自前瞻性纳入索尔福德肾脏研究的1946例NDD-CKD个体的数据用于研究NT-proBNP和Hs-cTnT与研究终点之间的关联。使用多变量Cox回归和竞争风险模型估计风险比或亚风险比以及95%置信区间（95%CI）。使用Harrell's C指数计算NT-proBNP和Hs-cTnT以及肾脏生物标志物（估算肾小球滤过率[eGFR]和尿白蛋白肌酐比值[uACR]）和弗雷明汉风险评分（FRS）的鉴别能力。使用在训练数据集中获得并在验证数据集中确认的回归系数生成特定终点风险评分。
在71.5个月的中位随访期间，发生了931例（47.8%）死亡、553例（28.4%）MACE和554例（28.5%）ESKD事件。基线NT-proBNP和Hs-cTnT升高与死亡率、MACE和ESKD风险显著增加独立相关，与FRS无关。将NT-proBNP、Hs-cTnT和FRS相结合对全因死亡率和MACE的预后准确性最高（C统计量分别为：0.713；95%CI：0.695-0.731和0.697；95%CI：0.673-0.721），而将NT-proBNP和Hs-cTnT与eGFR和uACR相结合在预测ESKD方面表现最佳（C统计量：0.821；95%CI：0.786-0.826）。
在NDD-CKD患者中，NT-proBNP和Hs-cTnT是全因死亡率、MACE和ESKD的预测指标，独立于eGFR和uACR。与单独或联合使用的肾脏生物标志物相比，将NT-proBNP和Hs-cTnT与eGFR和uACR相结合在ESKD风险预测方面表现更优。
