多中心回顾性研究NLR及PLR在评价利妥昔 单抗治疗特发性膜性肾病临床疗效的预测价值

Multicenter Retrospective Study on the Predictive Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Evaluating the Clinical Efficacy of Rituximab Treatment for Idiopathic Membranous Nephropathy

摘要: 目的：探讨中性粒细胞与淋巴细胞比值(NLR)及血小板与淋巴细胞比值(PLR)在评估特发性膜性肾病(IMN)患者利妥昔单抗(RTX)治疗临床疗效的预测价值。方法：回顾性安徽省多中心收集2018年1月至2024年9月诊断为IMN的患者且使用标准剂量RTX的IMN患者87例。依据用药前基线NLR、PLR中位数将纳入病例进行分组，分为低分位组(NLR ≤ 2.64) 44例、高分位组(NLR > 2.64) 43例；低分位组(PLR ≤ 144.85) 44例、高分位组(PLR > 144.85) 43例。分别收集两组患者的临床指标，分析NLR、PLR水平与不同随访时间段临床指标的相关性，探讨NLR、PLR与RTX治疗IMN疗效的相关性。结果：NLR低/高分位两组患者治疗前在性别、年龄、RTX剂量方案、红细胞、血红蛋白、血小板、血清白蛋白、24 h尿蛋白定量、抗磷脂酶A2受体(PLA2R)抗体、外周血B淋巴细胞计数等方面，差异均无统计学意义(P > 0.05)。低分位组血肌酐低于高分位组(P = 0.034)，且血清IgG高于高分位组(P = 0.035)。PLR高分位组估算肾小球滤过率(eGFR)低于低分位组(P = 0.020)。用药后1年随访，2组患者24 h尿蛋白定量较治疗前均有显著下降，血清白蛋白水平较治疗前均明显有所升高，血红蛋白差异无统计学意义。尿蛋白缓解方面，NLR分组患者治疗1年时总有效率为72.97%，其中低分位组临床缓解率显著高于高分位组(P = 0.013)；PLR低、高分位组治疗1年时缓解率比较，差异无统计学意义(P > 0.05)。NLR分组中，eGFR差异无统计学意义；PLR分组中，低分位组eGFR水平更高(P = 0.033)。Spearman相关性分析提示随访半年时基线NLR水平与血肌酐呈正相关(r = 0.220, P = 0.041)；随访1年时，基线NLR水平与24 h尿蛋白定量、血肌酐呈显著正相关，与血清白蛋白(r =−0.241, P = 0.038)呈显著负相关；基线PLR水平与尿蛋白定量呈正相关(r = 0.264, P = 0.023)。结论：NLR、PLR一定程度上可以反映IMN疾病严重程度；基线NLR水平与IMN患者使用RTX治疗的疗效预后相关。

Abstract: Objective: To evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the clinical efficacy of rituximab (RTX) treatment in patients with idiopathic membranous nephropathy (IMN). Methods: A retrospective multicenter study was conducted in Anhui Province, enrolling 87 IMN patients treated with standard-dose RTX between January 2018 and September 2024. Patients were stratified into low- and high-quartile groups based on median pre-treatment baseline NLR (cut-off: 2.64; 44 vs 43 patients) and PLR (cut-off: 144.85; 44 vs 43 patients). Collect clinical indicators for the two patient groups separately. The correlations between NLR/PLR levels and clinical indicators at various follow-up time points were analyzed to assess their association with RTX treatment outcomes. Results: There were no statistically significant differences between the NLR low/high quartile groups in terms of gender, age, RTX dosage regimen, red blood cell count, hemoglobin, platelet count, serum albumin, 24-hour urine protein quantification, anti-phospholipase A2 receptor (PLA2R) antibody levels, or peripheral blood B-lymphocyte count prior to treatment (P > 0.05). The low-NLR group had lower serum creatinine (P = 0.034) and higher serum IgG (P = 0.035) than the high-NLR group. The high-PLR group exhibited lower baseline eGFR than the low-PLR group (P = 0.020). At the 1-year follow-up, 24-hour urinary protein levels significantly decreased and serum albumin levels markedly increased from baseline in both groups, with no significant change in hemoglobin. The overall 1-year remission rate for NLR-stratified patients was 72.97%, with the low-NLR group achieving a significantly higher rate than the high-NLR group (P = 0.013). No significant difference in remission was found between PLR groups. Regarding renal function, eGFR did not differ significantly between NLR groups, whereas the low-PLR group maintained higher eGFR levels than the high-PLR group (P = 0.033). Spearman correlation analysis revealed baseline NLR correlated positively with serum creatinine at 6 months (r = 0.220, P = 0.041). At 1-year follow-up, baseline NLR showed positive correlations with 24-hour urinary protein (r = 0.264, P = 0.023) and serum creatinine, and a negative correlation with serum albumin (r = −0.241, P = 0.038). Baseline PLR was also positively correlated with 1-year urinary protein levels (r = 0.264, P = 0.023). Conclusions: NLR and PLR can to some extent reflect the severity of IMN; the baseline NLR level is related to the therapeutic prognosis of IMN patients treated with RTX.