ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2025, Vol. 34 ›› Issue (4): 301-308.DOI: 10.3969/j.issn.1006-298X.2025.04.001

• 论著 •    下一篇

粪菌 16sRNA 高通量测序联合血清白蛋白预测腹膜透析患者快速型腹膜溶质转运系数

  

  • 出版日期:2025-08-28 发布日期:2025-08-28

Fecal microbiota 16sRNA high-throughput sequencing combined with serum albumin for fast peritoneal solute transport rate prediction in peritoneal dialysis patients

  • Online:2025-08-28 Published:2025-08-28

摘要: 目的:探讨粪菌 16sRNA 高通量测序联合血清白蛋白(Alb)对腹膜透析(PD)患者快速型腹膜溶质转运系数(PSTR)的预测价值。
方法:纳入国家肾脏疾病临床医学研究中心回顾性患者队列(2004 年 1 月至 2024 年 1 月)和前瞻性患者队列(2024 年 5 月至 2024 年 10 月)。两个队列患者均根据置管后 30d 首次腹膜平衡试验(PET)透出液肌酐和血清肌酐浓度比值(D/Pcr)将患者分为非快速型 PSTR 组 [进一步分为低转运组(D/Pcr ≤0.49)和低平均转运组(D/Pcr 0.50~0.64)] 和快速型组(D/Pcr ≥0.65)。以多因素回归及受试者工作特征曲线(ROC)分析 Alb 预测快速型 PSTR 的能力,并以 David 提出的含性别、种族、Alb、钠参数的 PSTR 经验公式进行 Alb 预测能力的外部验证。前瞻性队列收集置管后 30d 行首次 PET 时粪便标本,-80℃冻存后统一完成粪菌 16sRNA 高通量测序,比较患者肠道菌群水平的差异,分析差异菌属联合 Alb 对快速型 PSTR 的判别价值。
结果:回顾性队列共纳入 1008 例 PD 患者,其中快速型 PSTR 组占比 26.9%。Logistic 回归分析提示,与快速型 PSTR 独立相关的变量包括收缩压、血尿酸和 Alb;与其他变量相比,Alb 水平判定快速型 PSTR 的 ROC 曲线下面积最大,且 Alb 预测能力与 David 公式差异无统计学意义 [AUC 95% CI 0.636 (0.593~0.680) vs 0.629 (0.589~0.670),P=0.480]。粪菌研究共纳入 50 例新入 PD 患者,低转运组、低平均转运组及快速型组在 Alb 水平差异具有统计学意义(P=0.012),三组间肠道菌群 α 多样性和 β 多样性差异均无统计学意义,菌群构成在门、纲、目、科水平差异均无统计学意义,但在属及种水平差异有统计学意义。瘤胃球菌属在低转运组相对丰度显著高于快速型组(P=0.018),瘤胃球菌属水平相对丰度与 D/Pcr 水平呈负相关(r=-0.351,P=0.013)。DeLong 检验显示,瘤胃球菌属水平相对丰度与 Alb 联合显著改善 Alb 判定快速型 PSTR 的预测价值 [AUC 95% CI 0.871 (0.733~0.979) vs 0.725 (0.554~0.895),P=0.04];粪菌联合 Alb 预测能力也显著优于 David 公式 [AUC 95% CI 0.668 (0.475~0.860),P<0.001]。
结论:Alb 水平是 PD 患者腹膜溶质转运功能独立预测因子,粪菌 16sRNA 高通量测序得出的瘤胃球菌相对丰度与 Alb 联合可显著提高其判定快速型 PSTR 的预测价值。

关键词: 腹膜透析, 快速型腹膜溶质转运系数, 肠道菌群, 高通量测序

Abstract: Objective: To explore the predictive value of combining fecal microbiota 16sRNA high-throughput sequencing with serum albumin (Alb) for the fast peritoneal solute transport rate (PSTR) in PD patients.
Methodology: In this center’s retrospective patient cohort (January 2004-January 2024), patients were divided into non-fast PSTR group and fast PSTR group based on the ratio of dialysate creatinine to serum creatinine from the first peritoneal equilibration test (PET) performed 30 days post-catheter insertion (D/Pcr=0.65). The ability of Alb to predict fast PSTR was analyzed using multivariate Logistic regression and receiver operating characteristic (ROC) analysis, and the external validation of Alb’s predictive capability was conducted using the PSTR empirical formula proposed by David, which includes parameters such as gender, race, Alb, and sodium. On the other hand, from May to October 2024, 50 newly admitted PD patients were recruited, and the first PET was performed 30 days post-catheter insertion. Concurrently, fecal samples were collected, frozen at -80℃, and subsequently subjected to high-throughput sequencing of fecal 16S rRNA. Patients were classified into low transport group (D/Pcr ≤0.49), low average transport group (D/Pcr 0.50-0.64), and fast PSTR group (D/Pcr ≥0.65) based on the D/Pcr ratio. The differences in intestinal microbiota levels among the three groups were compared, and significant differential bacterial genera were identified using linear discriminant analysis, analyzing the discriminative value of differential genera combined with Alb for fast PSTR.
Results: A retrospective cohort study included 1008 patients with PD, among which the fast PSTR group accounted for 26.9%. Logistic regression analysis indicated that the variables independently associated with fast PSTR included systolic blood pressure, uric acid, Alb. Compared to other variables, the level of Alb had the largest area under the ROC curve for determining fast PSTR. The predictive ability of Alb was not statistically significantly different from that of the David formula [AUC 95% CI 0.636 (0.593-0.680) vs 0.629 (0.589-0.670), P=0.480]. The fecal microbiota study included 50 newly admitted PD patients, revealing statistically significant differences in Alb levels among the low transport group, low average transport group and fast PSTR group (P=0.012). However, there were no statistically significant differences in the α and β diversity of intestinal microbiota among the three groups. The composition of the microbiota showed no statistically significant differences at the phylum, class, order, and family levels, but significant differences were observed at the genus and species levels. Linear discriminant analysis revealed that the relative abundance of the genus Ruminococcus in the low transport group was significantly higher than that in the fast PSTR group (P=0.018). Correlation analysis indicated a negative correlation between the relative abundance of Ruminococcus and D/Pcr levels (r=-0.351, P=0.013). The DeLong test demonstrated that the relative abundance of Ruminococcus significantly improved the predictive value of Alb for fast PSTR determination [AUC 95% CI 0.871 (0.733-0.979) vs 0.725 (0.554-0.895), P=0.04]; the predictive capability of fecal bacteria combined with Alb was also significantly superior to that of the David formula [AUC 95% CI 0.668 (0.475-0.860), P<0.001].
Conclusion: Serum Alb levels are independent predictors of peritoneal solute transport function in patients with PD. The relative abundance of Ruminococcus species derived from fecal 16S rRNA high-throughput sequencing, when combined with Alb levels, can significantly enhance the predictive value of the latter in determining the fast PSTR.

Key words: peritoneal dialysis, fast peritoneal solute transport rate, fecal microbiota, high-throughput sequencing