Elevated neutrophil-lymphocyte ratio combined with hyponatremia indicate poor prognosis in renal cell carcinoma

Background: Elevated neutrophil-lymphocyte ratio (NLR) and hyponatremia each predict poor prognosis in renal cell carcinoma (RCC). Since no previous studies have looked at the combined effect of these two prognostic markers, we examined how NLR and hyponatremia combined associates with mortality and hypothesized that elevated NLR and hyponatremia at RCC diagnosis and at RCC recurrence indicate poorer prognosis. Material and methods: Using Danish medical registries 1999–2015, we included 970 patients from two regions with incident RCC and a measurement of NLR and sodium. NLR was categorized as ≤3.0 and >3.0 and sodium as Results: At RCC diagnosis, 559 (57.6%) had NLR >3.0 and 240 (24.7%) had hyponatremia, the 5 year-survival rate was 35.2% in NLR > 3.0 vs. 69.2% in NLR ≤3.0, adjusted HR 1.8 (95% confidence intervals (CI), 1.4; 2.2). In patients with NLR >3.0 and concomitant hyponatremia vs. NLR ≤3.0 and normal sodium the 5-year survival rate was 21.7% vs. 73.2%, adjusted HR 2.8 (95% CI, 2.1; 3.8). At RCC recurrence, patients with NLR >3.0 and hyponatremia similarly had poorest survival, adjusted HR 3.6 (95% CI, 1.0; 12.8). Conclusion: Elevated NLR alone and in combination with hyponatremia at time of initial RCC diagnosis and at time of RCC recurrence are associated with poor prognosis. Combining these two prognostic markers yield a stronger association than NLR considered alone. This may impact prognostic prediction and its related therapeutic strategy.背景：中性粒细胞淋巴细胞比值（neutrophil-lymphocyte ratio, NLR）升高与低钠血症（hyponatremia）均可预测肾细胞癌（renal cell carcinoma, RCC）患者的不良预后。既往尚无研究探讨这两种预后标志物的联合效应，本研究旨在分析NLR与低钠血症联合对死亡率的关联，并提出假说：肾细胞癌确诊时及复发时的NLR升高合并低钠血症，提示患者预后更差。 材料与方法：依托1999-2015年丹麦医疗登记数据库，本研究纳入来自两个地区的970例新发肾细胞癌患者，所有受试者均具备NLR及血清钠检测数据。将NLR分为≤3.0与>3.0两组，血清钠则[原文未明确分类标准]。 结果：肾细胞癌确诊时，559例（57.6%）患者NLR>3.0，240例（24.7%）合并低钠血症；NLR>3.0组的5年生存率为35.2%，NLR≤3.0组则为69.2%，校正后的风险比（hazard ratio, HR）为1.8（95%置信区间（confidence interval, CI）：1.4~2.2）。在NLR>3.0且合并低钠血症的患者中，5年生存率为21.7%，而NLR≤3.0且血清钠正常的患者为73.2%，校正后的HR为2.8（95%CI：2.1~3.8）。在肾细胞癌复发患者中，NLR>3.0且合并低钠血症者同样生存率最差，校正后的HR为3.6（95%CI：1.0~12.8）。 结论：肾细胞癌初诊及复发时，单独的NLR升高，以及NLR升高合并低钠血症，均与不良预后相关。联合应用这两种预后标志物，相较单独使用NLR，可产生更强的预后关联效应。该发现或可对预后预测及相关治疗策略的制定产生影响。