目的探讨腹膜透析患者肠屏障功能与外周血中性粒细胞与淋巴细胞比值(neutrophil-tolymphocyteratio，NLR)的关系。方法选取2016年9月～2020年8月安徽医科大学第二附属医院肾脏内科规律随访的腹膜透析(peritonealdialysis，PD)患者(PD组)及同期规律门诊随访的慢性肾脏病(chronickidneydisease，CKD)3～5期非透析患者(CKD非透析组)为入组观察对象。收集临床数据，胃肠道症状及实验室指标，通过检测人体血清中二胺氧化酶(diamineoxidase，DAO)、血D-乳酸和血细菌内毒素水平评估肠屏障功能，采用多重线性回归模型分析2组NLR与DAO、D-乳酸及细菌内毒素水平之间的关联性。结果共纳入190例患者，PD组121例，CKD组69例。腹膜透析患者中有73例(60.3%)出现至少1种胃肠道症状，非透析患者中有37例(53.6%)出现至少1种胃肠道症状。PD组NLR水平高于CKD非透析组，差异有统计学意义(Z=2.223,P=0.026)；PD组D-乳酸及细菌内毒素水平高于CKD非透析组，差异有统计学意义(Z值分别为2.323、5.519，P值分别为0.020、＜0.001)。多重线性回归分析显示：PD组NLR与细菌内毒素(β=0.308，P=0.003)呈正相关，与DAO(β=-0.154，P=0.108)、D-乳酸(β=0.173，P=0.068)及年龄(β=-0.177，P=0.058)无统计学相关性；非透析组NLR与年龄(β=0.311，P=0.012)呈正相关，与D乳酸(β=0.162，P=0.197)、细菌内毒素(β=0.234，P=0.072)、DAO(β=-0.160，P=0.224)均无统计学相关性。结论多数腹膜透析患者具有消化道症状，同时腹膜透析患者D-乳酸及细菌内毒素水平较非透析患者升高，且腹膜透析患者的细菌内毒素与外周血NLR水平呈正相关，提示腹膜透析患者的肠屏障功能可能影响患者体内炎症反应。
Objective To investigate the relationship between intestinal barrier and the ratio of peripheral neutrophil to lymphocyte (NLR) in peritoneal dialysis (PD) patients. Methods The PD patients treated and regularly followed up in the Department of Nephrology, the Second Hospital of Anhui Medical University during September 2016 to August 2020 were enrolled in this study as the PD group. The chronic kidney disease patients at the stage 3～5 without dialysis and regularly followed up in our outpatient clinic during the same period were recruited as the CKD group. Clinical data, gastrointestinal symptoms and laboratory indices were collected. Intestinal barrier function was evaluated by serum diamine oxidase (DAO), d-lactic acid and bacterial endotoxin assays. Multivariate linear regression model was used to analyze the relationship between NLR and serum levels of DAO, d-lactic acid and bacterial endotoxin in the two groups. Results There were 121 cases in PD group and 69 cases in CKD group. At least one gastrointestinal symptom was present in 73 patients (60.3%) in PD group and 37 patients (53.6%) in CKD group. The NLR was significantly higher in PD group than in CKD group (Z=2.223, P=0.026). Serum d-lactic acid and bacterial endotoxin were significantly higher in PD group than in CKD group (Z=2.323 and 5.519 respectively, P=0.020 and＜0.001 respectively). Multivariate regression analysis showed that NLR in PD group was positively correlated with bacterial endotoxin (β=0.308, P=0.003), but not with DAO (β=-0.154, P=0.108), d-lactic acid (β=0.173, P=0.068) and age (β=-0.177, P=0.058); while NLR in CKD group was positively correlated with age (β=0.311, P=0.012) but not statistically correlated with serum d-lactic acid (β=0.162, P=0.197), bacterial endotoxin (β=0.234, P=0.072) and DAO (β=-0.160, P=0.224). Conclusion Gastrointestinal symptoms were present in most PD patients. Serum d-lactic acid and bacterial endotoxin were higher in PD patients than in non-dialysis CKD patients, and bacterial endotoxin was positively correlated with NLR in PD patients, suggesting that intestinal barrier function may affect the inflammatory responses in PD patients.
[1]Carrero J J, Stenvinkel P.Inflammation in end-stage renal disease--what have we learned in 10 years?[J].Semin Dial, 2010, 23(5):498-509
[2]Pupim L B, Himmelfarb J, Mcmonagle E, et al.Influence of initiation of maintenance hemodialysis on biomarkers of inflammation and oxidative stress[J].Kidney Int, 2004, 65(6):2371-9
[3]Stenvinkel P.Inflammation in end-stage renal failure: could it be treated?Nephrol Dial Transplant,2002,17 Suppl 8: 33-8; discussion 40.[J].Nephrol Dial Transplant, 2002, 17(Suppl 8):33-8
[4]Stenvinkel P, Alvestrand A.Inflammation in end-stage renal disease: sources,consequences,and therapy[J].Semin Dial, 2002, 15(5):329-37
[5]Teng F, Ye H, Xue T.Predictive value of neutrophil to lymphocyte ratio in patients with acute exacerbation of chronic obstructive pulmonary disease[J].PLoS One, 2018, 13(9):e0204377-
[6]Manco M, Putignani L, Bottazzo G F.Gut microbiota,lipopolysaccharides,and innate immunity in the pathogenesis of obesity and cardiovascular risk[J].Endocr Rev, 2010, 31(6):817-44
[7]Terpstra M L, Singh R, Geerlings S E, et al.Measurement of the intestinal permeability in chronic kidney disease[J].World J Nephrol, 2016, 5(4):378-88
[8]Vaziri N D, Zhao Y Y, Pahl M V.Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature,mechanisms,consequences and potential treatment[J].Nephrol Dial Transplant, 2016, 31(5):737-46
[9]王大海, 肖嘉新.谷氨酰胺联合异甘草酸镁对重症急性胰腺炎患者肠黏膜屏障功能及炎症介质的影响[J].医疗装备, 2020, 33(16):78-79
[10]鲁峻, 王剑, 黄鑫.美沙拉嗪联合双歧杆菌三联活菌治疗溃疡性结肠炎疗效及对患者肠黏膜屏障功能和血清炎症因子的影响[J].实用医院临床杂志, 2020, 17(04):221-224
[11]Perakis K E, Stylianou K G, Kyriazis J P, et al.Long-term complication rates and survival of peritoneal dialysis catheters: the role of percutaneous versus surgical placement[J].Semin Dial, 2009, 22(5):569-75
[12] Jiang C, Lin W, Wang L, et al.Fushen Granule, A Traditional Chinese Medicine, ameliorates intestinal mucosal dysfunction in peritoneal dialysis rat model by regulating p38MAPK signaling pathway[J].Journal of Ethnopharmacology, 2020, 251:-
[13] Naini A E, Karbalaie A, Abedini M, et al.Comparison of malnutrition in hemodialysis and peritoneal dialysis patients and its relationship with echocardiographic findings[J].Res Med Sci, 2016, 21::-
[14]Mizuno M, Suzuki Y, Ito Y.Future expectations of diagnostic approaches for treating endogenous peritonitis in patients on peritoneal dialysis[J].Intern Med, 2014, 53(6):647-
[15]Kahvecioglu S, Akdag I, Kiyici M, et al.High prevalence of irritable bowel syndrome and upper gastrointestinal symptoms in patients with chronic renal failure[J].J Nephrol, 2005, 18(1):61-6
[16]Wiedermann C J, Kiechl S, Dunzendorfer S, et al.Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: prospective results from the Bruneck Study[J].J Am Coll Cardiol, 1999, 34(7):1975-81
[17] Scaldaferri F, Pizzoferrato M, Gerardi V, et al.The gut barrier: new acquisitions and therapeutic approaches[J].Journal of clinical gastroenterology, 2012, 46 Suppl: :S12-7-
[18]Fuccio L, Guido A.Probiotics supplementation for the prevention of gastrointestinal radiation-induced side effects: the time is now[J].Am J Gastroenterol, 2013, 108(2):277-
[19]胡文兴, 刘敏.益生菌对维持性血液透析慢性肾脏病患者肠道菌群失调的影响[J].中国微生态学杂志, 2020, 32(11):1323-1326
[20]Wang I K, Wu Y Y, Yang Y F, et al.The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: a randomised,double-blind,placebo-controlled trial[J].Benef Microbes, 2015, 6(4):423-30
