尿微量蛋白及尿酶在强直性脊柱炎相关性肾病诊断中的意义
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摘要
目的:探讨尿微量蛋白及尿酶在强直性脊柱炎相关性肾病诊断中的意义。
     方法:入选强直性脊柱炎患者222例,均为2007年9月至2009年9月于我院风湿免疫科明确诊断为强直性脊柱炎的患者。其中男性201例,女性21例,年龄在12-53岁之间,平均(29±9.4)岁。每例患者均行尿α1微球蛋白、尿β2微球蛋白、尿微量白蛋白、尿免疫球蛋白、尿转铁蛋白及尿N-乙酰-β葡萄糖苷酶检查。将上述资料进行如下研究:(1)222例强直性脊柱炎患者中30例存在尿检异常,将其作为病变组(甲组),其余192例为尿检正常组(乙组)。另外选取正常对照组(丙组)30名,均为我院实习生,身体健康,均无肾脏疾患。采用SPSS13.0统计软件将三组患者的尿微量蛋白及尿酶进行对比研究,探讨尿微量蛋白及尿酶对强直性脊柱炎相关性肾病诊断的临床指导意义。(2)另将强直性脊柱炎尿检正常组(乙组)根据尿微量蛋白及尿酶阳性(至少一项超出正常上限)与否分为A组与B组,其中A组71例,B组121例。随诊观察6个月后统计两组发生尿检异常的病例数及百分比,进一步探讨尿微量蛋白及尿酶在早期发现AS相关性肾病的意义。(3)再将强直性脊柱炎患者中应用甲氨蝶呤+白芍总苷+来氟米特+NSAIDS方案治疗的病例,按尿酶阳性(超出正常上限)与否分为a组与b组,其中a组22例、b组30例,分别回顾两组患者应用甲氨蝶呤+白芍总苷+来氟米特+NSAIDS的情况,探讨尿N-乙酰-β葡萄糖苷酶在监测强直性脊柱炎药物性肾损害中的意义。
     结果:(1)强直性脊柱炎组(甲组+乙组)与正常对照组(丙组)的临床指标对比,结果表明强直性脊柱炎组的尿α1微球蛋白、β2微球蛋白、微量白蛋白、转铁蛋白及N-乙酰-β葡萄糖苷酶均高于正常对照组(P<0.05),有统计学意义;甲组与丙组的临床指标对比,结果表明甲组的尿α1微球蛋白、β2微球蛋白、微量白蛋白、尿免疫球蛋白、转铁蛋白及N-乙酰-β葡萄糖苷酶数值均高于丙组(P<0.05),存在统计学意义;乙组与丙组的临床指标对比,结果表明乙组的尿α1微球蛋白、β2微球蛋白及转铁蛋白均高于丙组(P<0.05),存在统计学意义;甲组与乙组的临床指标对比,结果表明甲组的尿α1微球蛋白、β2微球蛋白、微量白蛋白、尿免疫球蛋白、转铁蛋白及N-乙酰-β葡萄糖苷酶均高于乙组(P<0.05),存在统计学意义;甲组、乙组及全体AS(甲+乙)组的α1微球蛋白、β2微球蛋白、微量白蛋白、尿免疫球蛋白、转铁蛋白、N-乙酰-β葡萄糖苷酶的单项阳性率低,但联合检查的阳性率明显升高。
     (2)A组71例患者随诊6个月后追踪到58例,复查结果显示其中17例出现尿检异常,百分率为29%。B组121例患者随诊6个月后追踪到102例,复查结果显示其中7例出现尿检异常,百分率为7%。
     (3)a组应用甲氨蝶呤总量及NSAIDS用药时间较b组高,有统计学意义(P<0.05)。
     结论:
     1.α1微球蛋白、β2微球蛋白、微量白蛋白、尿免疫球蛋白、转铁蛋白及N-乙酰-β葡萄糖苷酶与AS相关性肾病肾脏改变严重程度呈正相关。
     2.联合应用α1微球蛋白、β2微球蛋白、微量白蛋白、尿免疫球蛋白、转铁蛋白及N-乙酰-β葡萄糖苷酶可能是发现早期AS相关性肾病的灵敏、可靠指标。
     3. N-乙酰-β葡萄糖苷酶可考虑作为AS患者检测药物肾毒性的指标。
Ankylosing spondylitis (ankylosing spondylitis, AS) is a seronegative spondyloarthropathy, it is a chronic inflammatory autoimmune disease which mainly involve the spine, axial, limb large joints and surrounding soft tissues. The pathogenesis of AS remains unclear, may related with genetic, environmental or infection. Most patients’lesions limited to part of the spine, or even limited to the sacral joint during his lifetime.While at the same time, there can be different degrees of heart, lungs, eyes, blood vessels, kidneys and other multi-organ diseases.
     The incidence of kidney damage reports in AS patients were various, data show that 15%~30% range. Currently AS kidney damage has not been given adequate attention in clinical, studies on it is still insufficient, and it is often overlooked result of increased renal, so it is especially important to early diagnosis of AS kidney damage.
     Currently there are different opinions on the AS renal damage, Beijing 301 Hospital, Academy of Sciences, Chen Xiang-mei proposed the concept of glomerulopathy associated with ankylosing spondylitis in 2000. Glomerulopathy associated with ankylosing spondylitis can be divided into IgA nephropathy, non-IgA mesangial proliferative quiet glomerulonephritis, membranous nephropathy, renal amyloidosis, acute interstitial nephritis and nephropathy associated with NSAIDS. Cases in this research are in accordance with the standard choice.Because of the limit of clinical laboratory and unable to carring out large-scale renal biopsy,this reasearch is not clearly distinguished from the primary AS kidney damage and kidney damage caused by drugs,and it will explore the early diagnosis of glomerulopathy associated with ankylosing spondylitis from the trace of urinary microprotein protein and urinary enzymes. As the detection of urinary microprotein and urinary enzymes is more sensitive and early than change of kidney function ,and more simple than renal biopsy,and noninvasive, it is suggested that periodic observation of urinary microprotein and urinary enzyme changes in AS patients has a reality and guiding meaning in early detection of kidney damage associated with AS.
     Objective:To study the value of urinary micriprotein and urinary enzyme to glomerulopathy associated with ankylosing spondylitis.
     Methods:Selected 222 patients with ankylosing spondylitis,who from September 2007 to December 2009 Division of Rheumatology at our hospital diagnosed as ankylosing spondylitis. Exclusion criteria: AS patients had no fever, diabetes, gout, hyperthyroidism, hypertension, acute and chronic nephritis, urinary tract infection, urinary tract stones, heart failure, cancer and other immune diseases such as rheumatoid history.The cases include 201 male, 21 female, aged 12 -53 years old, mean (29±9.4) years. Detection method: All patients who were selected on the morning after admission (> 8 hours <24 hours) collected early morning urine to send laboratory. Beckman Lx20 with the United States and other automatic biochemical analyzer measured the following indicators:α1-microglobulin,β2 microglobulin, albumin and urinary immunoglobulin, transferrin, and N-acetyl-βglucosidase. The cases in this research were randomly divided into the following groups : (1)30 cases in which there is abnormal urine test, as a disease group (Group A), and the remaining 192 cases the urine normal group (Group B). Also select the control group (Group C),including 30 cases, who are interns in our hospital, physical health, no kidney disease. Urinary abnormalities criteria: patients were excluded in each case of urinary tract infection, urinary protein (+) and above; urinary occult blood (+) and above, or high magnification> 3 / vision. SPSS13.0 statistical software used three groups of patients with urinary protein and NAG comparative study, statistical tests of the three indicators were the difference, and thus of ankylosing spondylitis patients compared with normal people and urinary trace protein in urine enzyme differences and what checks can be found early ankylosing spondylitis kidney damage in ankylosing spondylitis related to the early diagnosis of nephropathy reference. (2) Devide group B into two small group: group B1 and B2, there are 71 cases in group B1 and 121 cases in group B2. Follow up study of two groups after 6 months the number of cases occurring urinary abnormalities and percentage, further explore the significance of urine protein and urinary enzymes in early detection of glomerulopathy associated with ankylosing spondylitis. (3) Ankylosing spondylitis patients who were undergoing methotrexate+ TGP+ leflunomide+NSAIDs treatment will be devided into a and b groups by urease–positive (beyond the normal limit) or not, there are 22 cases in group a and 30 cases in group b. Recalling patients in the two groups with methotrexate+ TGP+ leflunomide+NSAIDs situation, then discuss the significance of urinary N-acetyl-βglucosidase in the monitoring of ankylosing spondylitis with renal drugs damage. The data of various groups are using SPSS13.0 statistical data processing software. Measurement data use t test. P<0.05 considered statistically significant.
     Results: (1) ankylosing spondylitis group (Group A + B) and normal control group (Group C) comparison of the clinical indicators, the results show that the ankylosing spondylitis group of urinaryα1-microglobulin,β2 microglobulin, trace albumin, transferrin, and N-acetyl-βglucosidase were higher than the control group (P <0.05), with statistical significance. Group A and B compared, the results show that all clinical indicators in group A are higher than group B,with statistical significance.All clinical indicators in ankylosing spondylitis patients, singal indicator has a low positive rate, but when together all of them, the positive rate has a obvious increasing.
     (2) we traced 58 cases in group B1 after 6 months, and the callback results show that there are 17cases among them appeared urinary abnormobility, the incidence rate is 29%. And we traced 102 cases in group B2 after 6 months, the callback results show that there are 7 cases appeared urinary abnormobility, has a 7% incidence rate.
     (3)The total dosage of methotrexate and the dispending time of NSAIDs in group a are higher than group b,with statistical significance(p<0.05).
     Conclusion:1.α1-microglobulin,β2 microglobulin, albumin and urinary immunoglobulin, transferrin, and N-acetyl-βglucosidase associated nephropathy and renal changes in AS was positively correlated.
     2. Combination ofα1-microglobulin,β2 microglobulin, albumin and urinary immunoglobulin, transferrin, and N-acetyl-βglucosidase is a diagnosis of AS may be associated nephropathy sensitive and reliable indicators.
     3. N-acetyl-βglucosidase could be a monitoring indicator for renal drug damage in ankylosing spondylitis patients.
引文
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    [1]郑良孝,李书忠.强直性脊柱炎的临床研究进展[J].颈腰痛杂志,2006,27(5):415-416.
    [2]Aaron S,Miller ML,Howard J.Complementation with HLA-A and HLA-D locus alleles in ankylosing spondylitis with peripherial arthritis[J]. 1985,(12).
    [3]Benjamin R,Parham P.HLA-B27 and disease:a consequence of inadv- ertent antigen presentation[J].1992.
    [4]黄烽,杨春花.强直性脊柱炎临床及免疫发病机制的研究进展[J].中国免疫学杂志,2001,17(6):281-4.
    [5]何永平,单爱琴,张荣国.21例强直性脊柱炎肾脏损害的分析[J].黑龙江医药科学,2002,25(1):106-107.
    [6]陈惠萍.强直性脊柱炎肾损伤[J].肾脏病与透析肾移植杂志,2006,15(4).
    [7]陈香美,刘文虎.强直性脊柱炎相关性肾损伤的临床分析[J].中华内科杂志,2000,39(5):338-340.
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    [9]Andersen G N.IgA-nephropathia in a patient with ankylosing spondylitis [J].1992 .
    [10]郭嘉隆,叶欣.强直性脊柱炎的肾脏损害[J].中国社区医学, 2004,20(14) .
    [11]Botey A,Torras A,Revert L.Membranous nephropathy in ankylosingspondylitis[J].1981.
    [12]Strobel ES,Fritschka E.Renal disease in ankylosing spondylitis:Review of the literature illustrated by case reports[J].1998.
    [13]单爱琴,何永平.强直性脊柱炎肾脏损害的临床病理分析[J].中国中西医结合肾病杂志,2004,5(7):401-402 .
    [14]Vilar MJ,Cury SE,Ferraz MB.Renal abnormalities in ankylosing spond- ylitis[J]. 1997,(1).
    [15]黄建萍.肾脏早期损伤的某些指标及其临床应用[J].中国实用儿科杂志,2003(8).
    [16]Nadir I,Topcu S,Kaptanoglu E.Puhnonary and renal involvement in ankylosing spondylitis[J].2003,(3).
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