【作者】 吴燕；

【导师】 薛勤；

【作者基本信息】 上海交通大学 ， 内科学（肾脏科）， 2016， 硕士

【摘要】 目的回顾性分析强直性脊柱炎(AS)继发肾脏损害的发病情况及其临床、实验室检查和病理特点,并探讨其相关危险因素,加强对AS继发肾脏损害的进一步认识。方法回顾性分析2003年8月-2015年3月上海市第六人民医院肾脏风湿科收治的1800例AS患者,筛选其中临床及实验室资料完整的AS患者1001例,分析其肾脏损伤(蛋白尿、血尿、eGFR及血肌酐升高)的基本特征、发病率、临床表现;AS继发肾脏损害与性别、病程、吸烟、关节疼痛部位、药物、HLA-B27、血小板、视黄醇结合蛋白等的相关性分析;并进一步探讨肾脏损害危险因素。另筛选其中503例AS患者分层分析了尿四联蛋白(即尿转铁蛋白、尿α1微球蛋白、尿IgG、尿微量白蛋白)在AS继发肾脏损害中的意义,以探索更早期的肾脏损害的生物学标志物;分析21例AS继发肾脏损害并行肾脏穿刺患者的临床、病理特点及治疗方案及转归。结果1001例AS患者中,继发肾脏损害有183例,占总AS患者的18.3%。其中,根据简化的MDRD得出eGFR降低的患者有12例,占1.2%;合并蛋白尿的患者有89例,占8.9%;血尿的患者有99例,占9.9%;血肌酐升高的有8例,占0.8%;既有血尿又有蛋白尿的患者有13例,占1.3%;急性肾功能不全的患者有3例,占0.3%。吸烟的AS患者肾脏损害的发病率显著高于不吸烟的患者,HLA-B27阳性的AS患者肾脏损害的发病率显著高于HLA-B27阴性的患者。二元Logistic回归分析提示男性、疼痛部位同时发生在中轴和外周关节、吸烟、NSAIDS用药史及视黄醇结合蛋白升高是AS继发肾脏损害的危险因素。在分析尿四联蛋白所收集的503例AS患者中,继发肾脏损害有167例,占总AS患者的33.2%。其中,蛋白尿的患者有50例,约10.0%;血尿的患者有45例,占9.9%;血肌酐升高的有0例,既有血尿又有蛋白尿的患者有10例,占2.0%;eGFR降低的有5例,占1.0%尿转铁蛋白升高有48例,占9.5%;尿α1微球蛋白升高有58例,占11.5%;尿IgG免疫球蛋白升高有70例,占13.9%;尿微量白蛋白升高有32例,占6.4%。尿四联蛋白的测定对于发现AS继发肾脏损害的发病率明显升高(P=0<0.05)。单纯AS继发尿四联蛋白升高的患者较单纯AS继发蛋白尿升高的患者血沉(P<0.05)和病程(P<0.05)有显著性差异。21例AS患者中肾脏穿刺活检病理为IgA肾病8例,占38.1%;系膜增生性肾小球肾炎7例,占33.3%;膜性肾病2例,占9.4%;轻微病变性肾小球肾炎1例,占4.8%;急性间质性肾炎1例,占4.8%;亚急性间质性肾炎1例,占4.8%;间质性肾炎合并系膜增生性肾炎1例,占4.8%。21患者在治疗后肾脏损害均有改善或稳定,其中8例AS继发IgA肾病患者治疗后的尿红细胞、24h尿蛋白较治疗前有显著改善(P<0.05);3例间质性肾炎在停用相应的诱发药物后,肾功能有明显改善。结论AS继发肾脏损害的发病率并不少见,临床表现可为蛋白尿、血尿、血尿合并蛋白尿、急性肾损伤、慢性肾功能不全及肾小管间质损伤等。AS继发肾脏损害与吸烟、关节疼痛的部位、NSADIS用药史、HLA-B27、血沉、CRP、血小板及视黄醇结合蛋白有显著的相关性。男性、疼痛部位同时发生在中轴和外周关节、吸烟、NSAIDS用药史及视黄醇结合蛋白升高是AS继发肾脏损害的危险因素。尿四联蛋白是AS继发肾脏损害早期的生物学标志,且在长病程及血沉高的AS的患者中更有意义。肾脏穿刺活检明确病理对AS继发肾脏损害患者意义重大,能指导临床用药,改善预后。更多还原

【Abstract】 Objective To fulfill retrospective analysis the clinical and laboratory characteristics of renal damage in Ankylosing spondylitis(AS)patients,to evaluate the risk factors and pathological features in kidney damage of AS patients,and to improve further understanding of renal involvement in AS.Methods We retrospectively reviewed the medical record of 1800 cases of ankylosing spondylitis who met the New York criteria from 2009.3 to 2015.3.Clinical and laboratory data of 1001 AS patients were analyzed about kidney damage(proteinuria,hematuria,eGFR decline and blood creatinine rise)of the basic characteristics,incidence,clinical manifestations,renal damage with gender,disease duration,smoke,pain correlation analysis site,drugs,HLA-B27,blood platelet and retinol binding protein;then further analysis of risk factors for kidney damage.Another selecting 503 patients further analyzed the urinary protein quadruplein,and it was significance to investigate earlier biomarkers;and finally selected 21 patients and all these patients were underwent percutaneous needle biopsy.We evaluated these patients with renal pathology and analyzed their baseline characteristics,clinical features,laboratory and urinalysis results,treatment protocols and treatment responses.Results 183 of 1001 AS patients had renal damages,accounting for 18.3%,Which,according to the simplified MDRD eGFR decreased patient obtained 12(1.2%)patients;89(8.9%)patients with proteinuria;99(9.9%)with hematuria;8(0.8%)patients had elevated creatinine;13 patients(1.3%)had both hematuria and proteinuria;acute renal failure patients in 3 patients(0.3%).The incidence of kidney damage in smoker was significantly higher than non-smokers,and the incidence of HLA-B27-positive patients with renal impairment were significantly higher than HLA-B27-negative patients.Binary variable Logistic regression analysis showed that male,the pain occurs simultaneously in axial and peripheral,smoking,NSAIDS medication history and retinol-binding protein were risk factors in the kidney damage of AS.There were 167(33.2%)patients of kidney damage in 503 patients.50(10.0%)patients had proteinuria;45(9.9%)patients had hematuria;elevated creatinine is 0 people,10(2.0%)had both proteinuria and hematuria;5(1.0%)patients had eGFR decreased;48(9.5%)patients had urinary transferrin increased;58(11.5%)patients had urinary α1-microglobulin increased;70(13.9%)patients had urinary IgG immune globulin increased;32(6.4%)patients elevated microalbuminuria.Quadruple urine protein(urinary transferrin,α1 microglobulin in urine,urinary IgG,microalbuminuria)raised incidence of kidney damage of AS(P <0.05).Simple AS quadruple urinary protein levels compared with 24 hours proteinuria in AS patients finding that elevated erythrocyte sedimentation rate(P <0.05)and duration(P<0.05)were significantly different.IgA nephropathy had the highest incidence of renal involvement(8 of 21,38%),followed by mesangial-proliferative glomerulonephritis(7 of 21,33.3%),membranous nephropathy(2 patients,9.5%)and rarely minor-lesion glomerulonephritis(1 patient,4.8%),acute interstitial nephritis(1 patient,4.8%),sub-acute interstitial nephritis(1 patient,4.8%)and interstitial nephritis with mesangial-proliferative nephropathy(1 patient,4.8%).After treatment,the levels of serum creatinine,red blood cell and proteinuria in urine in the patients were improved or stabilized,but,the differences of these changes do not have statistical significance except IgA nephropathy patients in this study.Moreover,the renal function of 3 patients with interstitial nephritis improved significantly after therapy and discontinuation of the induced drugs.Conclusions The incidence of kidney damage in AS patients is not rare,and is more common in smokers and in patients with HLA-B27-positive.Male,the pain occurs simultaneously in axial and peripheral,smoking,NSAIDS medication history and retinol-binding protein is risk factors in kidney damage of AS patients.Urinary protein quadruple AS is early biological markers in renal involvement patients,and more significant in patients with a long duration and elevated erythrocyte sedimentation rate.Renal biopsy is highly recommended to determine prognosis and decide the treatment protocol in clinical practice of renal involvement in ankylosing spondylitis.更多还原