间歇期痛风患者中性粒细胞/淋巴细胞比值的变化及其临床意义研究

背景　痛风作为最常见的炎症性关节炎，发病率呈逐渐上升趋势，其发生与高尿酸血症密切相关。而尿酸主要由肾脏排泄为主，目前评价尿酸经肾脏排泄水平的指标主要包括24 h尿尿酸、尿酸清除率、肌酐清除率、尿酸排泄分数（FEUA）、尿尿酸/尿肌酐等，而FEUA是更能准确反应肾脏排泄功能的一个指标。目的　探讨中性粒细胞/淋巴细胞比值（NLR）在间歇期痛风患者及FEUA分期中的变化，分析其是否可为FEUA分期提供新的参考指标。方法　选取2013年12月-2019年7月在川北医学院附属医院门诊及住院部就诊的386例间歇期痛风患者，同时选择与痛风患者年龄、性别相匹配的154例健康体检者。386例间歇期痛风患者有206例完成了24 h尿液检查作为痛风组，154例健康体检者中有39例完成24 h尿液检查作为对照组。根据FEUA对痛风患者进行分型，FEUA<7%为排泄减少型，FEUA 7%~12%为混合型，FEUA>12%为生成增多型［13］；收集研究对象的年龄、性别、身高、体质量、吸烟史、饮酒史、24 h尿量、24 h尿尿酸、24 h尿肌酐、血尿酸（UA）、肌酐（Cr）、FEUA、尿酸清除率、肌酐清除率、尿尿酸/尿肌酐、尿pH值、估算肾小球滤过率（eGFR）、首次就诊时的实验室检查〔包括白细胞计数（WBC）、中性粒细胞计数（GR）、淋巴细胞计数（LYM）、血小板计数（PLT）、平均红细胞体积（MCV）〕，以及不同分型痛风患者的受累关节数、痛风石、高原居住史、高血压、糖尿病、高脂血症、肾结石、痛风家族史情况。结果　痛风组BMI、吸烟史比例、饮酒史比例、24 h尿量、UA、GR、NLR高于对照组，FEUA、尿酸清除率、eGFR均低于对照组（P<0.05）。痛风患者NLR水平与FEUA呈正相关（rs=0.242，P<0.05），与肌酐清除率呈负相关（rs=-0.150，P<0.05）。206例痛风患者中尿酸排泄减少型183例（88.8%），混合型15例（7.3%），生成增多型8例（3.9%）。不同痛风分型患者饮酒史比例、肾结石比例、24 h尿量、血尿酸、肌酐、FEUA、尿酸清除率、肌酐清除率、尿尿酸/尿肌酐、GR、NLR比较，差异有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，饮酒、24 h尿量、血尿酸、FEUA、eGFR、NLR是痛风发生的影响因素（P<0.05）。NLR诊断痛风的ROC曲线下面积（AUC）95%CI为0.748（0.674，0.822），最佳截断值为1.76，灵敏度为78.16%，特异度为61.54%。NLR诊断排泄减少型痛风的AUC 95%CI为0.739（0.662，0.816），最佳截断值为1.76，灵敏度为77.60%，特异度为61.54%；NLR诊断混合型痛风的AUC 95%CI为0.758（0.601，0.915），最佳截断值为3.54，灵敏度为50.00%，特异度为100.00%；NLR诊断生成增多型痛风的AUC 95%CI为0.936（0.844，1.000），最佳截断值为4.07，灵敏度为75.00%，特异度为100.00%。结论　NLR与痛风发生密切相关，其在FEUA分期中具有重要辅助诊断价值，可指导临床用药，针对性选择降尿酸药物。

Changes and Clinical Significance of Neutrophil/Lymphocyte Ratio of Intercritical Gout Patients

Background　As the most common form of inflammatory arthritis，the morbidity of gout is gradually increasing，and its occurrence is closely related to hyperuricemia.Uric acid is mainly excreted by kidney.The current indicators to evaluate the level of uric acid excretion by kidney mainly include 24-hour urinary uric acid，clearance rate of uric acid and creatinine，fractional excretion of uric acid （FEUA） and urinary uric acid/urinary creatinine.FEUA is an indicator can reflect renal excretion more accurately.Objective　To investigate the changes of neutrophil/lymphocyte ratio （NLR） in gout patients during the intercritical period and FEUA staging，and to analyze whether it can provide a new reference index for FEUA staging.Methods　A total of 386 gout patients in intermittent phase who were treated in the outpatient and inpatient departments of the Affiliated Hospital of North Sichuan Medical College from December 2013 to July 2019 were selected，and 154 healthy persons matched with age and gender were selected.206 gout patients in intermittent phase who completed the 24-hour Urinalysis were treated as the gout group，and 39 of the 154 healthy persons who completed the 24-hour Urinalysis were treated as the control group.Gout group was classified according to the level of FEUA：FEUA<7% was the excretion-decreased type，FEUA 7%-12% was the mixed type，and FEUA>12% was the synthesis-increased type.The data of age，gender，height，body mass，smoking history，drinking，24-hour urine output，24-hour urinary uric acid，24-hour urine creatinine，blood uric acid （UA），creatinine clearance rate （Cr），FEUA，clearance rates of uric acid and creatinine，urinary uric acid/ creatinine，urinary pH，estimated glomerular filtration rate （eGFR） and the laboratory tests 〔including white blood cell count （WBC），neutrophil （GR），lymphocyte （LYM），platelet （PLT），average red blood cells （MCV）〕 in their first-time consultancy，the number of affected joints，the history situation of tophi，plateau living history，hypertension，diabetes，hyperlipidemia，kidney stones and family history of gout in different types of gout patients was collected.Results　BMI，smoking history ratio，drinking history ratio，24-hour urine output，UA，GR and NLR of the gout group were higher than the control group，and FEUA，uric acid clearance rate and eGFR of the gout group were lower than the control group （P<0.05）.NLR level was positively correlated with FEUA in gout patients（rs=0.242，P<0.05），negatively correlated with clearance rate of creatinine（rs=-0.150，P<0.05）.There were 206 subjects in the gout group，including 183 gout patients who had reduced uric acid excretion，15（7.3%） gout patients who had mixed type，and 8 （3.9%） gout patients who had increased uric acid excretion.There were significant differences in the proportion of drinking history，the proportion of renal stone，24-hour urine output，serum uric acid，serum creatinine，FUEA，uric acid clearance rate，creatinine clearance rate，uric acid/urinary creatinine，neutrophils and NLR maong different gout types patients （P<0.05）.Multivariate Logistic regression analysis showed that alcohol consumption，24-hour urine volume，serum uric acid，uric acid excretion fraction，eGFR and NLR were the influencing factors of gout occurrence （P < 0.05）.The area under the ROC curve （AUC） of NLR for the diagnosis of gout was 0.748 （0.674，0.822），the best cutoff value was 1.76，the sensitivity was 78.16%，and the specificity was 61.54%.The AUC of 95%CI of NLR for the diagnosis of excretion-decreased type was 0.739 （0.662，0.816），the best cutoff value was 1.76，the sensitivity was 77.60%，the specificity was 61.54%.The AUC 95%CI of NLR in the diagnosis of mixed gout was 0.758 （0.601，0.915），the best cutoff value was 3.54，the sensitivity was 50.00%，the specificity was 100.00%.The AUC 95%CI of NLR for the diagnosis of synthesis-increased type was 0.936 （0.844，1.000），the best cutoff value was 4.07，the sensitivity was 75.00%，and the specificity was 100.00%.Conclusion　NLR is closely related to the occurrence of gout，and it has important value in the staging of FEUA.It can guide contrapuntally selection of anti-uric acid drugs in clinical medication.